@article {pmid34571151, year = {2021}, author = {Yu, DH and Ying, N and Lian, ZH and Fa, YQ}, title = {The Alteration human of gut microbiota and metabolites before and after renal transplantation.}, journal = {Microbial pathogenesis}, volume = {}, number = {}, pages = {105191}, doi = {10.1016/j.micpath.2021.105191}, pmid = {34571151}, issn = {1096-1208}, abstract = {BACKGROUND: Recent studies have revealed that gut microbiota play an important part in the regulation of the immune function. With the development of newer detection methods, our cognition of the human gut microbiota continues to evolve with startling speed, but our understanding of the changes in the structure and function of gut microbiota before and after renal transplantation and the practical applications of this knowledge are still in their infancy.<br><br>METHODS: We prospectively recruited 10 renal transplant recipients and collected serial fecal specimens (N = 30) before the operation, and on the 7th and 30th day after the operation, and characterized their gut microbiota structure through deep sequencing of the 16S rRNA V4-V5 variable region and analyzed the presence of metabolites using LC-MS methods.<br><br>RESULTS: A decrease in the relative abundance of overall gut microbiota was detected in post-transplantation samples compared to that in pre-transplantation samples. Principal coordinate analysis (PCoA) inhibited a obvious separation between the three groups, and the linear discriminant analysis effect size (LEfSe) method showed that Clostridiales, Clostridia, Ruminococcaceae, Faecalibacterium, and Veillonellaceae were all significantly more abundant in the fecal specimens from the pre-transplantation group while Bacilli, Enterococcaceae, and Enterococcus were significantly more abundant in the fecal specimens from the four weeks post-transplantation group. Anaerostipes and Clostridia-bacterium were detected in the fecal samples from the one week post-transplantation group. Analysis of community composition did not reveal any significant difference between the pre-transplantation group and the post-transplantation group. The metabolic profiling of the volunteers before renal transplantation were distinct from the post-transplantation profiling, which gather together in PCA (Fig. 4A). After renal transplantation, the metabolic profiling of post-transplantation specimens revealed marked diversity and complexity.<br><br>CONCLUSIONS: Our research indicated remarkable variations in the gut microbiota and metabolites following renal transplantation, and that the gut microbiota and metabolites of patients with uremia were relatively stable and showed reasonable concordance. Distinct microbial compositions and metabolites were observed in patients after transplantation.}, }
@article {pmid34061001, year = {2021}, author = {Novais, F and Capela, J and Machado, S and Murillo-Rodriguez, E and Telles-Correia, D}, title = {Does Dysbiosis Increase the Risk of Developing Schizophrenia? - A Comprehensive Narrative Review.}, journal = {Current topics in medicinal chemistry}, volume = {21}, number = {11}, pages = {976-984}, doi = {10.2174/1568026621666210521163555}, pmid = {34061001}, issn = {1873-4294}, mesh = {Brain/*metabolism ; Central Nervous System/growth &amp; development/metabolism ; Dysbiosis/*complications/metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Inflammation/*metabolism ; Intestines/microbiology ; Prebiotics ; Probiotics/metabolism ; Schizophrenia/*etiology ; }, abstract = {BACKGROUND: There is increasing evidence regarding the influence of the intestinal microbiota on the disease processes of various organs and systems. Dysbiosis, that is, alteration of the composition and function of the microbiota may constitute an important risk factor for the development of mental disorders, namely, schizophrenia.<br><br>OBJECTIVE: This works aims to review current evidence regarding the pathological mechanisms leading from dysbiosis to schizophrenia and in particular the deficit syndrome in schizophrenia.<br><br>METHODS: Scientific articles from PubMed, SCOPUS, EMBASE, and Web of Science Core Collection published between September 2017 and December 2020 were included in this review.<br><br>RESULTS: The commensal intestinal flora plays an important role in neurodevelopment. In the presence of dysbiosis, this maturation gets disturbed, resulting in the modification of brain structures and inflammatory responses at the intestinal, systemic, and Central Nervous System (CNS) levels. These disturbances may be linked to the development of symptoms of the disease. The microbiota exerts its influence on the CNS through several pathways, however, in this paper we focused on the membrane hypothesis and the inflammatory hypothesis. We explored the evidence concerning the use of probiotics, prebiotics, and fecal transplants.<br><br>CONCLUSION: Although there is no consensus regarding the alterations that could constitute a risk factor for schizophrenia, some of the species appear to be more frequently altered, and their relationship with the host is dysregulated in patients at risk and with established schizophrenia, particularly in deficit schizophrenia.}, }
@article {pmid32897773, year = {2020}, author = {Lee, J and Venna, VR and Durgan, DJ and Shi, H and Hudobenko, J and Putluri, N and Petrosino, J and McCullough, LD and Bryan, RM}, title = {Young versus aged microbiota transplants to germ-free mice: increased short-chain fatty acids and improved cognitive performance.}, journal = {Gut microbes}, volume = {12}, number = {1}, pages = {1-14}, pmid = {32897773}, issn = {1949-0984}, support = {R01 HL134838/HL/NHLBI NIH HHS/United States ; R01 NS103592/NS/NINDS NIH HHS/United States ; RF1 AG058463/AG/NIA NIH HHS/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; }, mesh = {*Aging ; Animals ; Bacteria/classification/growth &amp; development ; Brain/immunology ; *Cognition ; Cognitive Dysfunction/etiology/*therapy ; Cytokines/blood ; Depression ; Fatty Acids, Volatile/analysis/*metabolism ; *Fecal Microbiota Transplantation ; Feces/chemistry/microbiology ; Gastrointestinal Microbiome/*physiology ; Germ-Free Life ; Leukocytes/immunology ; Male ; Memory ; Mice ; Mice, Inbred C57BL ; T-Lymphocyte Subsets/immunology ; }, abstract = {Aging is associated with cognitive decline and decreased concentrations of short-chain fatty acids (SCFAs) in the gut. SCFAs are significant in that they are protective to the gut and other organs. We tested the hypothesis that the aged gut microbiome alone is sufficient to decrease SCFAs in the host and produce cognitive decline. Fecal transplant gavages (FTGs) from aged (18-20 months) or young (2-3 months) male C57BL/6 mice into germ-free male C57BL/6 mice (N = 11 per group) were initiated at ~3 months of age. Fecal samples were collected and behavioral testing was performed over the study period. Bacterial community structures and relative abundances were measured in fecal samples by sequencing the bacterial 16S ribosomal RNA gene. Mice with aged and young microbiomes showed clear differences in bacterial β diversity at 30, 60, and 90 d (P = .001 for each) after FTGs. The fecal SCFAs, acetate, propionate, and butyrate (microbiome effect, P < .01 for each) were decreased in mice with an aged microbiome. Mice with an aged microbiome demonstrated depressive-like behavior, impaired short-term memory, and impaired spatial memory over the 3 months following the initial FTG as assessed by the tail suspension (P = .008), the novel object recognition (P < .001), and the Barnes Maze (P = .030) tests, respectively. We conclude that an aged microbiome alone is sufficient to decrease SCFAs in the host and to produce cognitive decline.}, }
@article {pmid32816619, year = {2020}, author = {Mitsinikos, FT and Chac, D and Schillingford, N and DePaolo, RW}, title = {Modifying macronutrients is superior to microbiome transplantation in treating nonalcoholic fatty liver disease.}, journal = {Gut microbes}, volume = {12}, number = {1}, pages = {1-16}, pmid = {32816619}, issn = {1949-0984}, mesh = {Animals ; Bacteria/classification/isolation &amp; purification ; Cytokines/metabolism ; *Diet, Fat-Restricted ; *Diet, Paleolithic ; Dietary Fiber/administration &amp; dosage ; *Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Liver/immunology/metabolism/pathology ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/*diet therapy/microbiology/pathology/therapy ; }, abstract = {Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver injury and liver transplantation in Western countries. The pathogenesis of NAFLD includes overnutrition-associated metabolic syndrome or the improper consumption of dietary macro- and micro-nutrients that either support or prevent disease development. This altered nutrient landscape has been linked to shifts within the gut microbiota which can exacerbate liver pathology and the progression of NAFLD. Treatment goals for NAFLD target lifestyle and dietary modifications that restrict calories and adjust macronutrient content. It is not well understood how different macronutrients alter the microbiota and whether the diet-educated microbiota contribute to the resolution of disease. We fed mice a diet high in fat, cholesterol and fructose for 6 weeks and then in two different arms of the study, intervened with either a diet high in saturated and polyunsaturated fats and fiber or low in fats and fiber. In a second set of experiments, we performed microbiota transplants using cecal contents from mice fed one of the intervention diets to assess whether the diet-educated microbiota could impact clinical outcomes in mice fed a NAFLD-inducing diet. Pathology, steatosis, ALT/AST levels, and liver cytokine levels were measured as primary outcomes. We found that despite different microbiota compositions, both of the intervention diets reversed the progression of NAFLD and dampened inflammation. In contrast, transplantation of cecal contents from the intervention diet-fed mice to mice receiving a NAFLD-inducing diet was unable to prevent disease progression, and, in some cases, worsened disease. These data underscore the importance of dietary modifications to treat NAFLD and caution against the use of microbiota transplantation in the absence of dietary and lifestyle modifications.}, }
@article {pmid34560321, year = {2021}, author = {Zuo, T and Wu, X and Wen, W and Lan, P}, title = {Gut Microbiome Alterations in COVID-19.}, journal = {Genomics, proteomics &amp; bioinformatics}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.gpb.2021.09.004}, pmid = {34560321}, issn = {2210-3244}, abstract = {Since the outset of the coronavirus disease 2019 (COVID-19) pandemic, the gut microbiome in COVID-19 has garnered substantial interest, given its significant roles in human health and pathophysiology. Accumulating evidence is unveiling that the gut microbiome is broadly altered in COVID-19, including the bacterial microbiome, mycobiome, and virome. Overall, the gut microbial ecological network is significantly weakened and becomes sparse in patients with COVID-19, together with a decrease in gut microbiome diversity. Beyond the existence of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the gut microbiome of patients with COVID-19 is also characterized by enrichment of opportunistic bacteria, fungi, and eukaryotic viruses, which are also associated with disease severity and presentation. Meanwhile, a multitude of symbiotic bacteria and bacteriophages are decreased in abundance in patients with COVID-19. Such gut microbiome features persist in a significant subset of patients with COVID-19 even after disease resolution, coinciding with 'long COVID' (also known as post-acute sequelae of COVID-19). The broadly-altered gut microbiome is largely a consequence of SARS-CoV-2 infection and its downstream detrimental effects on the systemic host immunity and the gut milieu. The impaired host immunity and distorted gut microbial ecology, particularly loss of low-abundance beneficial bacteria and blooms of opportunistic fungi including Candida, may hinder the re-assembly of the gut microbiome post COVID-19. Future investigation is necessary to fully understand the role of the gut microbiome in host immunity against SARS-CoV-2 infection, as well as the long-term effect of COVID-19 on the gut microbiome in relation to the host health after the pandemic.}, }
@article {pmid34557498, year = {2021}, author = {Liptak, R and Gromova, B and Gardlik, R}, title = {Fecal Microbiota Transplantation as a Tool for Therapeutic Modulation of Non-gastrointestinal Disorders.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {665520}, doi = {10.3389/fmed.2021.665520}, pmid = {34557498}, issn = {2296-858X}, abstract = {Fecal microbiota transplantation has been primarily investigated as a therapeutic tool for a number of gut disorders. Optimistic results from clinical studies on Clostridium difficile infection, inflammatory bowel disease and irritable bowel syndrome have stimulated the expansion of possible indications in which FMT might represent a game changing approach. Microbial dysbiosis was shown in a number of non-gastrointestinal disorders. Moreover, FMT was proven to be effective in therapy of numerous animal models of disease. However, only a proportion of these disorders have been addressed in clinical studies using FMT. These include obesity, non-alcoholic fatty liver disease, cardiovascular inflammation and neurological disorders such as autism, depression and Parkinson's disease. Results from preclinical and clinical studies also outlined possible molecular mechanisms that contribute to alleviation of the disease. These range from increasing the circulating levels of microbial metabolites (trimethylamine N-oxide, lipopolysaccharide, short chain fatty acids) to stimulation of the enteric nervous system. Several methodological shortcomings are still to be addressed; however, positive results of the clinical studies indicate that further investigation of FMT as a therapeutic tool for non-gastrointestinal disorders can be expected in upcoming years.}, }
@article {pmid34557102, year = {2021}, author = {Sun, Z and Li, J and Wang, W and Liu, Y and Liu, J and Jiang, H and Lu, Q and Ding, P and Shi, R and Zhao, X and Yuan, W and Tan, X and Shi, X and Xing, Y and Mao, T}, title = {Qingchang Wenzhong Decoction Accelerates Intestinal Mucosal Healing Through Modulation of Dysregulated Gut Microbiome, Intestinal Barrier and Immune Responses in Mice.}, journal = {Frontiers in pharmacology}, volume = {12}, number = {}, pages = {738152}, doi = {10.3389/fphar.2021.738152}, pmid = {34557102}, issn = {1663-9812}, abstract = {Inflammatory bowel disease (IBD), a group of multifactorial and inflammatory infirmities, is closely associated with dysregulation of gut microbiota and host metabolome, but effective treatments are currently limited. Qingchang Wenzhong Decoction (QCWZD) is an effective and classical traditional herbal prescription for the treatment of IBD and has been proved to attenuate intestinal inflammation in a model of acute colitis. However, the role of QCWZD in recovery phase of colitis is unclear. Here, we demonstrated that mice treated with QCWZD showed a faster recovery from dextran sulfate sodium (DSS)-induced epithelial injury, accompanied by reduced mucosal inflammation and attenuated intestinal dysbiosis using bacterial 16S rRNA amplicon sequencing compared to those receiving sterile water. The protective effects of QCWZD are gut microbiota dependent, as demonstrated by fecal microbiome transplantation and antibiotics treatment. Gut microbes transferred from QCWZD-treated mice displayed a similar role in mucosal protection and epithelial regeneration as QCWZD on colitis in mice, and depletion of the gut microbiota through antibiotics treatments diminished the beneficial effects of QCWZD on colitis mice. Moreover, metabolomic analysis revealed metabolic profiles alternations in response to the gut microbiota reprogrammed by QCWZD intervention, especially enhanced tryptophan metabolism, which may further accelerate intestinal stem cells-mediated epithelial regeneration to protect the integrity of intestinal mucosa through activation of Wnt/β-catenin signals. Collectively, our results suggested that orally administrated QCWZD accelerates intestinal mucosal healing through the modulation of dysregulated gut microbiota and metabolism, thus regulating intestinal stem cells-mediated epithelial proliferation, and hold promise for novel microbial-based therapies in the treatment of IBD.}, }
@article {pmid33196144, year = {2021}, author = {Timmis, K}, title = {Microbiome transplants to save the planetary surface biosphere.}, journal = {Environmental microbiology reports}, volume = {13}, number = {1}, pages = {50-53}, doi = {10.1111/1758-2229.12906}, pmid = {33196144}, issn = {1758-2229}, mesh = {Adult ; Animals ; Bacteria/classification/genetics/growth &amp; development/isolation &amp; purification ; Behavior ; *Ecosystem ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Planets ; Sheep ; Young Adult ; }, }
@article {pmid34552194, year = {2021}, author = {Brunse, A and Deng, L and Pan, X and Hui, Y and Castro-Mejía, JL and Kot, W and Nguyen, DN and Secher, JB and Nielsen, DS and Thymann, T}, title = {Fecal filtrate transplantation protects against necrotizing enterocolitis.}, journal = {The ISME journal}, volume = {}, number = {}, pages = {}, pmid = {34552194}, issn = {1751-7370}, support = {8022-00188B//Det Frie Forskningsråd (Danish Council for Independent Research)/ ; }, abstract = {Necrotizing enterocolitis (NEC) is a life-threatening gastrointestinal disorder afflicting preterm infants, which is currently unpreventable. Fecal microbiota transplantation (FMT) is a promising preventive therapy, but the transfer of pathogenic microbes or toxic compounds raise concern. Removal of bacteria from donor feces by micropore filtering may reduce this risk of bacterial infection, while residual bacteriophages could maintain the NEC-preventive effects. We aimed to assess preclinical efficacy and safety of fecal filtrate transplantation (FFT). Using fecal material from healthy suckling piglets, we compared rectal FMT administration (FMT, n = 16) with cognate FFT by either rectal (FFTr, n = 14) or oro-gastric administration (FFTo, n = 13) and saline (CON, n = 16) in preterm, cesarean-delivered piglets as models for preterm infants. We assessed gut pathology and analyzed mucosal and luminal bacterial and viral composition using 16S rRNA gene amplicon and meta-virome sequencing. Finally, we used isolated ileal mucosa, coupled with RNA-Seq, to gauge the host response to the different treatments. Oro-gastric FFT completely prevented NEC, which was confirmed by microscopy, whereas FMT did not perform better than control. Oro-gastric FFT increased viral diversity and reduced Proteobacteria relative abundance in the ileal mucosa relative to control. An induction of mucosal immunity was observed in response to FMT but not FFT. As preterm infants are extremely vulnerable to infections, rational NEC-preventive strategies need incontestable safety profiles. We show in a clinically relevant animal model that FFT, as opposed to FMT, efficiently prevents NEC without any recognizable side effects.}, }
@article {pmid34226737, year = {2021}, author = {Mocanu, V and Zhang, Z and Deehan, EC and Kao, DH and Hotte, N and Karmali, S and Birch, DW and Samarasinghe, KK and Walter, J and Madsen, KL}, title = {Fecal microbial transplantation and fiber supplementation in patients with severe obesity and metabolic syndrome: a randomized double-blind, placebo-controlled phase 2 trial.}, journal = {Nature medicine}, volume = {27}, number = {7}, pages = {1272-1279}, pmid = {34226737}, issn = {1546-170X}, support = {//CIHR/Canada ; }, mesh = {Dietary Fiber/*therapeutic use ; Dietary Supplements ; Double-Blind Method ; Fecal Microbiota Transplantation/*methods ; Female ; Fermentation/physiology ; Gastrointestinal Microbiome/physiology ; Humans ; Insulin Resistance/*physiology ; Male ; Metabolic Syndrome/*therapy ; Middle Aged ; Obesity, Morbid/*therapy ; Proof of Concept Study ; }, abstract = {Fecal microbial transplantation (FMT) from lean donors to patients with obesity has been associated with metabolic benefits, yet results so far have been inconsistent. In this study, we tested the application of daily fiber supplementation as an adjunct to FMT therapy to modulate cardiometabolic outcomes. We performed a double-blind randomized trial in patients with severe obesity and metabolic syndrome receiving oral FMT, to test high-fermentable (HF) and low-fermentable (LF) fiber supplements (NCT03477916). Seventy participants were randomized to the FMT-HF (n = 17), FMT-LF (n = 17), HF (n = 17) and LF (n = 19) groups. The primary outcome was the assessment of change in insulin sensitivity from baseline to 6 weeks using the homeostatic model assessment (HOMA2-IR/IS). After 6 weeks, only patients in the FMT-LF group had significant improvements in HOMA2-IR (3.16 ± 3.01 at 6 weeks versus 3.77 ± 3.57 at baseline; P = 0.02). No difference in HOMA2-IR was observed over this period for those in the FMT-HF group (3.25 ± 1.70 at 6 weeks versus 3.17 ± 1.72 at baseline; P = 0.8), the HF group (3.49 ± 1.43 at 6 weeks versus 3.26 ± 1.33 at baseline; P = 0.8) or the LF group (3.76 ± 2.01 at 6 weeks versus 3.56 ± 1.81 at baseline; P = 0.8). Interventions were safe and well-tolerated with no treatment-attributed serious adverse events. We provide proof of concept for the use of a single-dose oral FMT combined with daily low-fermentable fiber supplementation to improve insulin sensitivity in patients with severe obesity and metabolic syndrome.}, }
@article {pmid33547298, year = {2021}, author = {Normington, C and Moura, IB and Bryant, JA and Ewin, DJ and Clark, EV and Kettle, MJ and Harris, HC and Spittal, W and Davis, G and Henn, MR and Ford, CB and Wilcox, MH and Buckley, AM}, title = {Biofilms harbour Clostridioides difficile, serving as a reservoir for recurrent infection.}, journal = {NPJ biofilms and microbiomes}, volume = {7}, number = {1}, pages = {16}, pmid = {33547298}, issn = {2055-5008}, mesh = {Aged ; Aged, 80 and over ; Bacteriological Techniques ; Biofilms/drug effects/*growth &amp; development ; Clostridioides difficile/drug effects/*pathogenicity ; Clostridium Infections/drug therapy/*microbiology ; Colon/drug effects/*microbiology ; Fecal Microbiota Transplantation ; Humans ; Middle Aged ; Models, Biological ; Reinfection/drug therapy/microbiology ; Vancomycin/pharmacology ; }, abstract = {C. difficile infection (CDI) is a worldwide healthcare problem with ~30% of cases failing primary therapy, placing a burden on healthcare systems and increasing patient morbidity. We have little understanding of why these therapies fail. Here, we use a clinically validated in vitro gut model to assess the contribution of biofilms towards recurrent disease and to investigate biofilm microbiota-C. difficile interactions. Initial experiments show that C. difficile cells became associated with the colonic biofilm microbiota and are not depleted by vancomycin or faecal microbiota transplant therapies. We observe that transferring biofilm encased C. difficile cells into a C. difficile naïve but CDI susceptible model induces CDI. Members of the biofilm community can impact C. difficile biofilm formation by acting either antagonistically or synergistically. We highlight the importance of biofilms as a reservoir for C. difficile, which can be a cause for recurrent infections.}, }
@article {pmid34550085, year = {2021}, author = {Chinna Meyyappan, A and Sgarbossa, C and Vazquez, G and Bond, DJ and Müller, DJ and Milev, R}, title = {The Safety and Efficacy of Microbial Ecosystem Therapeutic-2 in People With Major Depression: Protocol for a Phase 2, Double-Blind, Placebo-Controlled Study.}, journal = {JMIR research protocols}, volume = {10}, number = {9}, pages = {e31439}, doi = {10.2196/31439}, pmid = {34550085}, issn = {1929-0748}, abstract = {BACKGROUND: The gut-brain axis is a bidirectional signaling pathway between the gastrointestinal tract and the brain; it is being studied because of its potential influence in mediating mood, anxiety, and other neuropsychiatric symptoms. Previous research examining the effects of gut microbiota on neuropsychiatric disorders suggests that gut repopulation treatments such as probiotics, microbe therapy, and fecal microbiota transplantation show promising results in treating symptoms of anxiety and depression. This study explores the use of an alternative gut repopulation treatment to fecal microbiota transplantation, known as Microbial Ecosystem Therapeutic (MET)-2, as an intervention against symptoms of depression. MET-2 is a daily, orally administered capsule containing 40 bacterial strains purified from a single healthy donor.<br><br>OBJECTIVE: The primary aim of this study is to assess changes in mood in people with major depression that occur pre-, post-, and during the administration of MET-2. The secondary aims are to assess changes in anxiety symptoms, blood biomarker concentrations, and the level of repopulation of healthy gut bacteria as a response to treatment.<br><br>METHODS: In this study, we will recruit 60 adults aged between 18 and 45 years old with major depression and randomly assign them to treatment or placebo groups. Patients in the treatment group will receive MET-2 once a day for 6 weeks, whereas patients in the placebo group will receive a matching placebo for 6 weeks. Participants will complete biweekly visits during the treatment period and a follow-up visit at 2 weeks post treatment. As a primary outcome measure, participants' mood will be assessed using the Montgomery-Asberg Depression Rating Scale. Secondary outcome measures include changes in mood, anxiety, early stress, gastrointestinal symptoms, and tolerability of MET-2 treatment using a series of clinical scales and changes in blood markers, particularly immunoglobulins (Igs; IgA, IgG, and IgM) and inflammatory markers (C-reactive protein, tumor necrosis factor-α, transforming growth factor-β, interleukin-6, and interleukin-10). Changes in the relative abundance, diversity, and level of engraftment in fecal samples will be assessed using 16S rRNA sequencing. All data will be integrated to identify biomarkers that could indicate disease state or predict improvement in depressive symptoms in response to MET-2 treatment.<br><br>RESULTS: Given the association between the gut microbiome and depression, we hypothesized that participants receiving MET-2 would experience greater improvement in depressive symptoms than those receiving placebo owing to the recolonization of the gut microbiome with healthy bacteria modulating the gut-brain axis connection.<br><br>CONCLUSIONS: This study is the first of its kind to evaluate the safety and efficacy of a microbial therapy such as MET-2 in comparison with placebo for major depressive disorder. We hope that this study will also reveal the potential capabilities of microbial therapies to treat other psychiatric illnesses and mood disorders.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov NCT04602715; https://clinicaltrials.gov/ct2/show/NCT04602715.<br><br>DERR1-10.2196/31439.}, }
@article {pmid34549762, year = {2021}, author = {Yan, X and Wang, Y and Ren, XY and Liu, XY and Ma, JM and Song, RL and Wang, XH and Dong, Y and Yu, AX and Fan, QQ and Wei, J and She, GM}, title = {Gut dysbiosis correction contributes to the hepatoprotective effects of Thymus quinquecostatus Celak extract against alcohol through the gut-liver axis.}, journal = {Food &amp; function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d1fo01117k}, pmid = {34549762}, issn = {2042-650X}, abstract = {Alcoholic liver disease (ALD) is a major health issue globally due to the consumption of alcoholic beverages. Thymus quinquecostatus Celak is a food additive and an edible herb that is widely used in Asia and possesses hepatoprotective activity, but the underlying mechanisms behind this protective activity are not completely understood. The purpose of this study was to investigate the hepatoprotective effects of Thymus quinquecostatus Celak extract (TQE) against ALD as well as the underlying mechanism based on gut microbiota and the gut-liver axis. TQE supplementation markedly alleviated chronic alcohol-induced liver injury in C57 mice. TQE also ameliorated gut barrier dysfunction induced by alcohol. Consequently, the activation of the lipopolysaccharide (LPS) translocation-mediated TLR4 pathway and the subsequent inflammatory response and ROS overproduction in the liver were suppressed. Meanwhile, alcohol-induced gut microbiota dysbiosis was also corrected by TQE. To further investigate the contribution of gut dysbiosis correction to the beneficial effects of TQE on ALD, a fecal microbiota transplantation study was conducted. TQE-manipulated gut microbiota transplantation markedly counteracted the alcohol-induced gut dysbiosis in the recipient mice. In parallel with gut dysbiosis correction, liver damage was partly ameliorated in the recipient mice. Gut barrier dysfunction, endotoxemia, TLR4 pathway induction as well as downstream inflammatory response and ROS overproduction were also partly suppressed due to gut dysbiosis correction in alcohol-fed recipient mice. In summary, these results suggest that gut dysbiosis correction contributes to the hepatoprotective effects of TQE against alcohol through the gut-liver axis.}, }
@article {pmid33783420, year = {2021}, author = {Sartelli, M and Ansaloni, L and Biffl, WA and Coccolini, F and De Simone, B and Leppaniemi, A and Kluger, Y and Tolonen, M and Moore, EE and Catena, F}, title = {World Society of Emergency Surgery-American Association for the Surgery of Trauma Guidelines for management of Clostridioides (Clostridium) difficile infection in surgical patients: An executive summary.}, journal = {The journal of trauma and acute care surgery}, volume = {91}, number = {2}, pages = {422-426}, doi = {10.1097/TA.0000000000003196}, pmid = {33783420}, issn = {2163-0763}, mesh = {Anti-Bacterial Agents/therapeutic use ; Antimicrobial Stewardship ; Clostridioides difficile/*pathogenicity ; Clostridium Infections/diagnosis/*therapy ; Enterocolitis, Pseudomembranous/etiology/prevention &amp; control ; Fecal Microbiota Transplantation/methods/trends ; Humans ; Incidence ; Infection Control/methods/trends ; Postoperative Complications/*therapy ; *Practice Guidelines as Topic ; Risk Factors ; Societies, Medical ; }, abstract = {ABSTRACT: In the last three decades, the dramatic worldwide increase in incidence and severity of Clostridioides difficile infection (CDI) (formerly Clostridium difficile infection) has made CDI a global public health challenge. Surgery is a known risk factor for development of CDI yet surgery is also a treatment option in severe cases of CDI. The World Society of Emergency Surgery guidelines for management of CDI in surgical patients were published in 2015. In 2019, the guidelines were revised and updated according to the grading of recommendations assessment, development and evaluation methodology. This executive summary is intended to consolidate knowledge on the management of CDI focusing on aspects that a general and emergency surgeon should know about the prevention and the management of CDI, by providing a practical and concise version of the original guidelines.}, }
@article {pmid34539138, year = {2021}, author = {Kang, YB and Cai, Y}, title = {Faecal microbiota transplantation enhances efficacy of immune checkpoint inhibitors therapy against cancer.}, journal = {World journal of gastroenterology}, volume = {27}, number = {32}, pages = {5362-5375}, pmid = {34539138}, issn = {2219-2840}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Immune Checkpoint Inhibitors ; *Neoplasms/drug therapy ; Radioimmunotherapy ; }, abstract = {Even though immune checkpoint inhibitors (ICIs) are effective on multiple cancer types, there are still many non-responding patients. A possible factor put forward that may influence the efficacy of ICIs is the gut microbiota. Additionally, faecal microbiota transplantation may enhance efficacy of ICIs. Nevertheless, the data available in this field are insufficient, and relevant scientific work has just commenced. As a result, the current work reviewed the latest research on the association of gut microbiota with ICI treatments based on anti-programmed cell death protein 1 antibody and anti- cytotoxic T-lymphocyte-associated protein 4 antibody and explored the therapeutic potential of faecal microbiota transplantation in combination with ICI therapy in the future.}, }
@article {pmid33053357, year = {2020}, author = {Leclercq, S and Le Roy, T and Furgiuele, S and Coste, V and Bindels, LB and Leyrolle, Q and Neyrinck, AM and Quoilin, C and Amadieu, C and Petit, G and Dricot, L and Tagliatti, V and Cani, PD and Verbeke, K and Colet, JM and Stärkel, P and de Timary, P and Delzenne, NM}, title = {Gut Microbiota-Induced Changes in β-Hydroxybutyrate Metabolism Are Linked to Altered Sociability and Depression in Alcohol Use Disorder.}, journal = {Cell reports}, volume = {33}, number = {2}, pages = {108238}, doi = {10.1016/j.celrep.2020.108238}, pmid = {33053357}, issn = {2211-1247}, mesh = {3-Hydroxybutyric Acid/blood/*metabolism ; Alcoholism/blood/*complications/*microbiology ; Animals ; Anti-Bacterial Agents/pharmacology ; Bacteria/drug effects ; Behavior, Animal/drug effects ; Brain/physiopathology ; Depression/blood/*complications/*microbiology ; Diet, Ketogenic ; Dysbiosis/blood/complications/microbiology ; Ethanol ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Homeostasis/drug effects ; Humans ; Inflammation/blood/complications ; Intestines/drug effects/pathology ; Lipolysis/drug effects ; Liver/drug effects/metabolism ; Male ; Metabolic Networks and Pathways/drug effects ; Mice, Inbred C57BL ; Myelin Sheath/metabolism ; Permeability ; *Social Behavior ; Tissue Donors ; }, abstract = {Patients with alcohol use disorder (AUD) present with important emotional, cognitive, and social impairments. The gut microbiota has been recently shown to regulate brain functions and behavior but convincing evidence of its role in AUD is lacking. Here, we show that gut dysbiosis is associated with metabolic alterations that affect behavioral (depression, sociability) and neurobiological (myelination, neurotransmission, inflammation) processes involved in alcohol addiction. By transplanting the gut microbiota from AUD patients to mice, we point out that the production of ethanol by specific bacterial genera and the reduction of lipolysis are associated with a lower hepatic synthesis of β-hydroxybutyrate (BHB), which thereby prevents the neuroprotective effect of BHB. We confirm these results in detoxified AUD patients, in which we observe a persisting ethanol production in the feces as well as correlations among low plasma BHB levels and social impairments, depression, or brain white matter alterations.}, }
@article {pmid34543718, year = {2021}, author = {Wah, M and Vázquez, MAM and Padilla, FJB}, title = {.}, journal = {Gastroenterologia y hepatologia}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.gastrohep.2021.08.008}, pmid = {34543718}, issn = {0210-5705}, abstract = {The incidence of inflammatory bowel disease (IBD) is increasing. Microbiome is one of the most important factors in its development and affects the different clinical outcomes of IBD patients depending on its composition and different alterations. We conducted a systematic review to discuss the association between microbiome and IBD in terms of immune regulation, and therapies that can modify microbiota. A comprehensive systematic literature search was performed through April 2020 in PubMed, Web of Science, the Cochrane Library, and clinicaltrials.gov. Inclusion criteria required IBD immune regulation and alternate therapeutics for IBD. This analysis helps explain the multifactorial origin of microbiome diversity including normal immune regulation, immune pathophysiology of IBD, and shows the evidence of several therapeutic targets to change microbiome in patients with IBD, such as prebiotics, probiotics, antibiotics, fecal microbiota transplant, and others.}, }
@article {pmid33926922, year = {2021}, author = {Kragsnaes, MS and Kjeldsen, J and Horn, HC and Munk, HL and Pedersen, JK and Just, SA and Ahlquist, P and Pedersen, FM and de Wit, M and Möller, S and Andersen, V and Kristiansen, K and Kinggaard Holm, D and Holt, HM and Christensen, R and Ellingsen, T}, title = {Safety and efficacy of faecal microbiota transplantation for active peripheral psoriatic arthritis: an exploratory randomised placebo-controlled trial.}, journal = {Annals of the rheumatic diseases}, volume = {80}, number = {9}, pages = {1158-1167}, doi = {10.1136/annrheumdis-2020-219511}, pmid = {33926922}, issn = {1468-2060}, mesh = {Adult ; Antirheumatic Agents/therapeutic use ; Arthritis, Psoriatic/microbiology/*therapy ; Dysbiosis/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Male ; Methotrexate/therapeutic use ; Middle Aged ; Proof of Concept Study ; Treatment Outcome ; }, abstract = {OBJECTIVES: Although causality remains to be established, targeting dysbiosis of the intestinal microbiota by faecal microbiota transplantation (FMT) has been proposed as a novel treatment for inflammatory diseases. In this exploratory, proof-of-concept study, we evaluated the safety and efficacy of FMT in psoriatic arthritis (PsA).<br><br>METHODS: In this double-blind, parallel-group, placebo-controlled, superiority trial, we randomly allocated (1:1) adults with active peripheral PsA (≥3 swollen joints) despite ongoing treatment with methotrexate to one gastroscopic-guided FMT or sham transplantation into the duodenum. Safety was monitored throughout the trial. The primary efficacy endpoint was the proportion of participants experiencing treatment failure (ie, needing treatment intensification) through 26 weeks. Key secondary endpoints were change in Health Assessment Questionnaire Disability Index (HAQ-DI) and American College of Rheumatology (ACR20) response at week 26.<br><br>RESULTS: Of 97 screened, 31 (32%) underwent randomisation (15 allocated to FMT) and 30 (97%) completed the 26-week clinical evaluation. No serious adverse events were observed. Treatment failure occurred more frequently in the FMT group than in the sham group (9 (60%) vs 3 (19%); risk ratio, 3.20; 95% CI 1.06 to 9.62; p=0.018). Improvement in HAQ-DI differed between groups (0.07 vs 0.30) by 0.23 points (95% CI 0.02 to 0.44; p=0.031) in favour of sham. There was no difference in the proportion of ACR20 responders between groups (7 of 15 (47%) vs 8 of 16 (50%)).<br><br>CONCLUSIONS: In this first preliminary, interventional randomised controlled trial of FMT in immune-mediated arthritis, we did not observe any serious adverse events. Overall, FMT appeared to be inferior to sham in treating active peripheral PsA.<br><br>TRIAL REGISTRATION NUMBER: NCT03058900.}, }
@article {pmid33414033, year = {2021}, author = {Fuhri Snethlage, CM and Nieuwdorp, M and Hanssen, NMJ}, title = {Faecal microbiota transplantation in endocrine diseases and obesity.}, journal = {Best practice &amp; research. Clinical endocrinology &amp; metabolism}, volume = {35}, number = {3}, pages = {101483}, doi = {10.1016/j.beem.2020.101483}, pmid = {33414033}, issn = {1878-1594}, mesh = {*Diabetes Mellitus, Type 2/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Insulin Resistance ; Obesity/therapy ; }, abstract = {The prevalence of type 1 (T1D) and type 2 diabetes mellitus (T2D) has greatly increased worldwide over the last century. Although the exact pathophysiology of both these conditions is distinct and still largely unknown, T1D as well as T2D, have been linked to distinct perturbations of the gut microbiome. Faecal microbiota transplantation (FMT) is a potent, and if performed well, a safe method to modulate the composition of the gut microbiome and thus positively influences the course of these hyperglycaemic conditions in humans. In this review, we provide an overview of how FMT is commonly performed and summarise how this procedure may reduce the insulin-resistance driving T2D, and the underlying auto-immunity driving T1D. Insights derived from FMT studies in T1D and T2D may help identify beneficial microbiota and associated metabolites that may serve as future treatments for these conditions.}, }
@article {pmid34527093, year = {2021}, author = {Ashraf, MF and Tageldin, O and Nassar, Y and Batool, A}, title = {Fecal Microbiota Transplantation in Patients With Recurrent Clostridium difficile Infection: A Four-Year Single-Center Retrospective Review.}, journal = {Gastroenterology research}, volume = {14}, number = {4}, pages = {237-243}, pmid = {34527093}, issn = {1918-2805}, abstract = {Background: Clostridium difficile infection (CDI) is a common cause of hospital and community-acquired diarrhea with an annual incidence of 453,000 cases in the USA. The white race, female gender, and age over 65 years are known risk factors. Recurrence of CDI is a major problem in patients taking antibiotics for prolonged periods. These patients are observed to have reduced diversity of the intestinal microbiome. Fecal microbiota transplantation (FMT) can restore the healthy flora in the gut, thus breaking the cycle of recurrent infection. Our study aimed to analyze the efficacy of FMT and the recurrence of CDI after FMT. We also aimed to investigate the effects of comorbidities on the outcome of FMT.<br><br>Methods: After obtaining approval from the institutional review board, we included 64 patients who had received FMT at our institution from October 2015 to November 2019. All the patients over 16 years of age in both inpatient and outpatient settings were included. Patients under 16 years of age and patients treated without FMT were excluded. Frozen stool from a standardized stool bank (OpenBiome) was used. The thawed specimen was instilled into the terminal ileum or the cecum. Patients were followed up for the next 1 year for analysis of improvement in symptoms, recurrence, and repeat FMT.<br><br>Results: On the 2-months follow-up, 75% of patients reported symptomatic improvement, 15.6% reported no improvement while 9.4% did not follow up. Twenty-six (40.6%) patients had CDI recurrence in the following year; and 69.2% of patients with recurrence underwent a repeat FMT. There was no statistically significant correlation between CDI recurrence and the age (P value = 0.68), gender (P value = 0.61), previous use of proton pump inhibitors (PPIs, P value = 0.11) or antibiotics (P value = 0.45). There was a statistically significant correlation noted with the use of immunosuppressants and recurrence (P value = 0.04).<br><br>Conclusions: FMT is a successful treatment modality for refractory and recurrent CDI. Repeat treatments can be beneficial if there is a lack of initial response. Being immunosuppressed with medications is associated with the risk of recurrence.}, }
@article {pmid34525908, year = {2021}, author = {Zanza, C and Romenskaya, T and Thangathurai, D and Ojetti, V and Saviano, A and Abenavoli, L and Robba, C and Cammarota, G and Franceschi, F and Piccioni, A and Longhitano, Y}, title = {Microbiome in Critical illness: An Unconventional and Unknown Ally.}, journal = {Current medicinal chemistry}, volume = {}, number = {}, pages = {}, doi = {10.2174/0929867328666210915115056}, pmid = {34525908}, issn = {1875-533X}, abstract = {BACKGROUND: The digestive tract represents an interface between the external environment and the body where the interaction of a complex polymicrobial ecology has an important influence on health and disease. The physiological mechanisms that are altered during the hospitalization and in the intensive care unit (ICU) contribute to the pathobiota's growth. Intestinal dysbiosis occurs within hours of being admitted to ICU. This may be due to different factors, such as alterations of normal intestinal transit, administration of variuos medications or alterations in the intestinal wall which causes a cascade of events that will lead to the increase of nitrates and decrease of oxygen concentration, liberation of free radicals.<br><br>OBJECTIVE: This work aims to report the latest updates on the microbiota's contribution to developing sepsis in patients in the ICU department. In this short review were reviewed the latest scientific findings on the mechanisms of intestinal immune defenses performed both locally and systemically. In addition, we considered it necessary to review the literature to report the current best treatment strategies to prevent the infection spread which can bring systemic infections in patients admitted to ICU.<br><br>MATERIAL AND METHODS: This review has been written to answer at three main questions: what are the main intestinal flora's defense mechanisms that help us to prevent the risk of developing systemic diseases on a day-to-day basis? What are the main dysbiosis' systemic abnormalities? What are the modern strategies that are used in the ICU patients to prevent the infection spread? Using the combination of following keywords: microbiota and ICU, ICU and gut, microbiota and critical illness, microbiota and critical care, microbiota and sepsis, microbiota and infection, gastrointestinal immunity,in the Cochrane Controlled Trials Register, the Cochrane Library, medline and pubmed, google scholar, ovid/wiley. Finally, we reviewed and selected 72 articles. We also consulted the site ClinicalTrials.com to find out studies that are recently conducted or ongoing.<br><br>RESULTS: The critical illness can alter intestinal bacterial flora leading to homeostasis disequilibrium. Despite numerous mechanisms, such as epithelial cells with calciform cells that together build a mechanical barrier for pathogenic bacteria, the presence of mucous associated lymphoid tissue (MALT) which stimulates an immune response through the production of interferon-gamma (IFN-y) and THN-a or by stimulating lymphocytes T helper-2 produces anti-inflammatory cytokines. But these defenses can be altered following a hospitalization in ICU and lead to serious complications such as acute respiratory distress syndrome (ARDS), health care associated pneumonia (HAP) and ventilator associated pneumonia (VAP), Systemic infection and multiple organ failure (MOF), but also in the development of coronary artery disease (CAD). In addition, the microbiota has a significant impact on the development of intestinal complications and the severity of the SARS-COVID-19 patients.<br><br>CONCLUSION: The microbiota is recognized as one of the important factors that can worsen the clinical conditions of patients who are already very frailty in intensive care unit. At the same time, the microbiota also plays a crucial role in the prevention of ICU associated complications. By using the resources, we have available, such as probiotics, symbiotics or fecal microbiota transplantation (FMT), we can preserve the integrity of the microbiota and the GUT, which will later help maintain homeostasis in ICU patients.}, }
@article {pmid34444932, year = {2021}, author = {Gibiino, G and Sartini, A and Gitto, S and Binda, C and Sbrancia, M and Coluccio, C and Sambri, V and Fabbri, C}, title = {The Other Side of Malnutrition in Inflammatory Bowel Disease (IBD): Non-Alcoholic Fatty Liver Disease.}, journal = {Nutrients}, volume = {13}, number = {8}, pages = {}, pmid = {34444932}, issn = {2072-6643}, mesh = {Colitis, Ulcerative/epidemiology ; Fecal Microbiota Transplantation/methods ; Female ; Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*epidemiology ; Intestines/pathology ; Male ; Malnutrition/*epidemiology ; Metabolic Syndrome/epidemiology ; Non-alcoholic Fatty Liver Disease/*epidemiology/therapy ; Nutritional Status ; Obesity/epidemiology ; Prevalence ; Risk Factors ; }, abstract = {Steatohepatitis and hepatobiliary manifestations constitute some of the most common extra-intestinal manifestations of Inflammatory Bowel Disease (IBD). On the other hand, non-alcoholic fatty liver disease (NAFLD) affects around 25% of the world's population and is attracting ever more attention in liver transplant programs. To outline the specific pathways linking these two conditions is a pressing task for 21st-century researchers. We are accustomed to expecting the occurrence of fatty liver disease in obese people, but current evidence suggests that there are several different pathways also occurring in underweight patients. Genetic factors, inflammatory signals and microbiota are key players that could help in understanding the entire pathogenesis of NAFLD, with the aim of defining the multiple expressions of malnutrition. In the current review, we summarize the most recent literature regarding the epidemiology, pathogenesis and future directions for the management of NAFLD in patients affected by IBD.}, }
@article {pmid34226711, year = {2021}, author = {Montassier, E and Valdés-Mas, R and Batard, E and Zmora, N and Dori-Bachash, M and Suez, J and Elinav, E}, title = {Probiotics impact the antibiotic resistance gene reservoir along the human GI tract in a person-specific and antibiotic-dependent manner.}, journal = {Nature microbiology}, volume = {6}, number = {8}, pages = {1043-1054}, pmid = {34226711}, issn = {2058-5276}, support = {/WT_/Wellcome Trust/United Kingdom ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Adult ; Anti-Bacterial Agents/*administration &amp; dosage ; Bacteria/classification/*drug effects/*genetics/isolation &amp; purification ; Bacterial Proteins/*genetics/metabolism ; Cohort Studies ; *Drug Resistance, Bacterial ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects ; Gastrointestinal Tract/microbiology ; Humans ; Male ; Metagenome/drug effects ; Middle Aged ; Probiotics/*administration &amp; dosage ; Young Adult ; }, abstract = {Antimicrobial resistance poses a substantial threat to human health. The gut microbiome is considered a reservoir for potential spread of resistance genes from commensals to pathogens, termed the gut resistome. The impact of probiotics, commonly consumed by many in health or in conjunction with the administration of antibiotics, on the gut resistome is elusive. Reanalysis of gut metagenomes from healthy antibiotics-naïve humans supplemented with an 11-probiotic-strain preparation, allowing direct assessment of the gut resistome in situ along the gastrointestinal (GI) tract, demonstrated that probiotics reduce the number of antibiotic resistance genes exclusively in the gut of colonization-permissive individuals. In mice and in a separate cohort of humans, a course of antibiotics resulted in expansion of the lower GI tract resistome, which was mitigated by autologous faecal microbiome transplantation or during spontaneous recovery. In contrast, probiotics further exacerbated resistome expansion in the GI mucosa by supporting the bloom of strains carrying vancomycin resistance genes but not resistance genes encoded by the probiotic strains. Importantly, the aforementioned effects were not reflected in stool samples, highlighting the importance of direct sampling to analyse the effect of probiotics and antibiotics on the gut resistome. Analysing antibiotic resistance gene content in additional published clinical trials with probiotics further highlighted the importance of person-specific metagenomics-based profiling of the gut resistome using direct sampling. Collectively, these findings suggest opposing person-specific and antibiotic-dependent effects of probiotics on the resistome, whose contribution to the spread of antimicrobial resistance genes along the human GI tract merit further studies.}, }
@article {pmid34521450, year = {2021}, author = {Wang, M and Zhu, Z and Lin, X and Li, H and Wen, C and Bao, J and He, Z}, title = {Gut microbiota mediated the therapeutic efficacies and the side effects of prednisone in the treatment of MRL/lpr mice.}, journal = {Arthritis research &amp; therapy}, volume = {23}, number = {1}, pages = {240}, pmid = {34521450}, issn = {1478-6362}, support = {82074217//National Natural Science Foundation of China/ ; 81973829//National Natural Science Foundation of China/ ; LY21H270006//Natural Science Foundation of Zhejiang Province/ ; }, abstract = {BACKGROUND: Growing evidences indicate that the alterations in gut microbiota are associated with the efficacy of glucocorticoids (GCs) in the treatment of systemic lupus erythematosus (SLE). However, there is no evidence to prove whether gut microbiota directly mediates the effects of GCs.<br><br>METHODS: Using the MRL/lpr mice, this study firstly addressed the effects of three doses of prednisone on gut microbiota. Then, this study used fecal microbiota transplantation (FMT) to transfer the gut microbiota of prednisone-treated MRL/lpr mice into the blank MRL/lpr mice to reveal whether the gut microbiota regulated by prednisone had similar therapeutic efficiency and side effects as prednisone.<br><br>RESULTS: The effects of prednisone on gut microbiota were dose-dependent in the treatment of MRL/lpr mice. After transplantation into MRL/lpr mice, prednisone-regulated gut microbiota could alleviate lupus, which might be due to decreasing Ruminococcus and Alistipes and retaining the abundance of Lactobacillus. However, prednisone-regulated gut microbiota did not exhibit side effects as prednisone. The reason might be that the pathogens upregulated by prednisone could not survive in the MRL/lpr mice as exogenous microbiota, such as Parasutterella, Parabacteroides, and Escherichia-Shigella.<br><br>CONCLUSIONS: These data demonstrated that the transplantation of gut microbiota may be an effective method to obtain the therapeutic effects of GCs and avoid the side effects of GCs.}, }
@article {pmid33796102, year = {2021}, author = {Chen, H and Shen, L and Liu, Y and Ma, X and Long, L and Ma, X and Ma, L and Chen, Z and Lin, X and Si, L and Chen, X}, title = {Strength Exercise Confers Protection in Central Nervous System Autoimmunity by Altering the Gut Microbiota.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {628629}, pmid = {33796102}, issn = {1664-3224}, mesh = {Animals ; *Autoimmunity ; Bacteria/immunology/*metabolism ; Central Nervous System/*immunology ; Dysbiosis ; Encephalomyelitis, Autoimmune, Experimental/immunology/microbiology/*prevention &amp; control ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Intestine, Small/immunology/*microbiology ; Mice, Inbred C57BL ; Neuroimmunomodulation ; *Physical Conditioning, Animal ; *Resistance Training ; T-Lymphocytes, Regulatory/immunology ; Th17 Cells/immunology ; }, abstract = {Exercise therapy including endurance training and resistance training is a promising non-pharmacological therapy in patients with multiple sclerosis (MS). Recent studies have revealed that exercise exerts beneficial impacts on gut microbiota. However, the role of gut microbiota in the immune benefits of strength exercise (SE; one of resistance training) in central nervous system (CNS) autoimmunity is barely known. Here, we observed that 60-min SE ameliorated disease severity and neuropathology in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. SE increased the abundance and diversity of the gut microbiota, and decreased Firmicutes/Bacteroidetes ratio (F/B ratio) and intestinal mucosal permeability, and enrichment of several short-chain fatty acid (SCFA)-producing bacteria. Furthermore, SE reduced Th17 responses and increased Treg responses in the small intestine lymphoid tissues. Compared to the control group, microbiota-depleted mice receiving SE microbiome fecal transplants had lower disease severity and neuropathology scores. These results uncovered a protective role of SE in neuroimmunomodulation effects partly via changes to the gut microbiome.}, }
@article {pmid32364071, year = {2020}, author = {Tarasiuk, A and Eibl, G}, title = {Nutritional Support and Probiotics as a Potential Treatment of IBD.}, journal = {Current drug targets}, volume = {21}, number = {14}, pages = {1417-1427}, doi = {10.2174/1389450121666200504075519}, pmid = {32364071}, issn = {1873-5592}, support = {POIR.04.04.00-00-420C/2017//Kosciuszko Foundation (The American Centre of Polish Culture, Foundation)/ ; 502-03/1-156-04/502-14-361-18//Medical University of Lodz/ ; }, mesh = {Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/etiology/microbiology/*therapy ; *Nutrition Therapy ; Probiotics/*therapeutic use ; }, abstract = {The pathogenesis of inflammatory bowel disease (IBD) remains unknown. However, there is growing evidence that the increase in the overall incidence of IBD relates to the improvement of sanitary and hygienic conditions of the society leading to lower exposure to both bacterial and parasitic infections. IBD is incurable and characterized by alternating periods of exacerbation and remission of symptoms. Therefore, the main goal of treatment strategies in IBD patients is the most effective maintenance of clinical and endoscopic remission, which does allow patients to function normally for a significant part of life. Taking into account the evidence from different areas, there is a strong rationale supporting the concept that bacteria are important in gut inflammation and that probiotic bacteria may modulate the host-microbe interaction in a way that is directly beneficial to IBD patients along with nutritional support. In this review, we focus on the potential role of gastrointestinal microbiota in the pathogenesis of IBD and the possible value of probiotics, prebiotics, and symbiotics as well as nutritional support in the treatment of IBD.}, }
@article {pmid34516460, year = {2021}, author = {Singh, T and Bedi, P and Bumrah, K and Gandhi, D and Arora, T and Verma, N and Schleicher, M and Rai, MP and Garg, R and Verma, B and Sanaka, MR}, title = {Fecal Microbiota Transplantation and Medical Therapy for Clostridium difficile Infection: Meta-analysis of Randomized Controlled Trials.}, journal = {Journal of clinical gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MCG.0000000000001610}, pmid = {34516460}, issn = {1539-2031}, abstract = {GOALS: The aim was to assess the effectiveness of fecal microbiota transplantation (FMT) against medical therapy (MT).<br><br>BACKGROUND: FMT has shown good outcomes in the treatment of Clostridium difficile infection (CDI). We aimed to conduct a systematic review and meta-analysis to compare the effectiveness of FMT versus MT for CDI.<br><br>STUDY: We performed a comprehensive search to identify randomized controlled trials comparing FMT against MT in patients with CDI. Outcomes of interest were clinical cure as determined by the resolution of diarrhea and/or negative C. difficile testing. Primary CDI is defined as the first episode of CDI confirmed endoscopically or by laboratory analysis. Recurrent C. difficile infection (RCDI) is defined as laboratory or endoscopically confirmed episode of CDI after at least 1 course of approved antibiotic regimen.<br><br>RESULTS: A total of 7 studies with 238 patients were included in meta-analysis. Compared with MT, FMT did not have a statistically significant difference for clinical cure of combined primary and RCDI after first session [risk ratio (RR): 1.52, 95% confidence interval (CI): 0.90, 2.58; P=0.12; I2=77%] and multiple sessions of FMT (RR: 1.68; CI: 0.96, 2.94; P=0.07; I2=82%). On subgroup analysis, FMT has statistically higher rate of response than MT (RR: 2.41; CI: 1.20, 4.83; I2=78%) for RCDI. However, for primary CDI there is no statistically significant difference between FMT and MT (RR: 1.00; CI: 0.72, 1.39; I2=0%).<br><br>CONCLUSION: As per our analysis, FMT should not be utilized for every patient with CDI. It is more effective in RCDI, but the results were not significant in patients with primary CDI.}, }
@article {pmid34514619, year = {2021}, author = {Suchodolski, JS}, title = {Analysis of the gut microbiome in dogs and cats.}, journal = {Veterinary clinical pathology}, volume = {}, number = {}, pages = {}, doi = {10.1111/vcp.13031}, pmid = {34514619}, issn = {1939-165X}, abstract = {The gut microbiome is an important immune and metabolic organ. Intestinal bacteria produce various metabolites that influence the health of the intestine and other organ systems, including kidney, brain, and heart. Changes in the microbiome in diseased states are termed dysbiosis. The concept of dysbiosis is constantly evolving and includes changes in microbiome diversity and/or structure and functional changes (eg, altered production of bacterial metabolites). Molecular tools are now the standard for microbiome analysis. Sequencing of microbial genes provides information about the bacteria present and their functional potential but lacks standardization and analytical validation of methods and consistency in the reporting of results. This makes it difficult to compare results across studies or for individual clinical patients. The Dysbiosis Index (DI) is a validated quantitative PCR assay for canine fecal samples that measures the abundance of seven important bacterial taxa and summarizes the results as one single number. Reference intervals are established for dogs, and the DI can be used to assess the microbiome in clinical patients over time and in response to therapy (eg, fecal microbiota transplantation). In situ hybridization or immunohistochemistry allows the identification of mucosa-adherent and intracellular bacteria in animals with intestinal disease, especially granulomatous colitis. Future directions include the measurement of bacterial metabolites in feces or serum as markers for the appropriate function of the microbiome. This article summarizes different approaches to the analysis of gut microbiota and how they might be applicable to research studies and clinical practice in dogs and cats.}, }
@article {pmid34513724, year = {2021}, author = {Innes, AJ and Mullish, BH and Ghani, R and Szydlo, RM and Apperley, JF and Olavarria, E and Palanicawandar, R and Kanfer, EJ and Milojkovic, D and McDonald, JAK and Brannigan, ET and Thursz, MR and Williams, HRT and Davies, FJ and Marchesi, JR and Pavlů, J}, title = {Fecal Microbiota Transplant Mitigates Adverse Outcomes Seen in Patients Colonized With Multidrug-Resistant Organisms Undergoing Allogeneic Hematopoietic Cell Transplantation.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {684659}, doi = {10.3389/fcimb.2021.684659}, pmid = {34513724}, issn = {2235-2988}, abstract = {The gut microbiome can be adversely affected by chemotherapy and antibiotics prior to hematopoietic cell transplantation (HCT). This affects graft success and increases susceptibility to multidrug-resistant organism (MDRO) colonization and infection. We performed an initial retrospective analysis of our use of fecal microbiota transplantation (FMT) from healthy donors as therapy for MDRO-colonized patients with hematological malignancy. FMT was performed on eight MDRO-colonized patients pre-HCT (FMT-MDRO group), and outcomes compared with 11 MDRO colonized HCT patients from the same period. At 12 months, survival was significantly higher in the FMT-MDRO group (70% versus 36% p = 0.044). Post-HCT, fewer FMT-MDRO patients required intensive care (0% versus 46%, P = 0.045) or experienced fever (0.29 versus 0.11 days, P = 0.027). Intestinal MDRO decolonization occurred in 25% of FMT-MDRO patients versus 11% non-FMT MDRO patients. Despite the significant differences and statistically comparable patient/transplant characteristics, as the sample size was small, a matched-pair analysis between both groups to non-MDRO colonized control cohorts (2:1 matching) was performed. At 12 months, the MDRO group who did not have an FMT had significantly lower survival (36.4% versus 61.9% respectively, p=0.012), and higher non relapse mortality (NRM; 60.2% versus 16.7% respectively, p=0.009) than their paired non-MDRO-colonized cohort. Conversely, there was no difference in survival (70% versus 43.4%, p=0.14) or NRM (12.5% versus 31.2% respectively, p=0.24) between the FMT-MDRO group and their paired non-MDRO cohort. Collectively, these data suggest that negative clinical outcomes, including mortality associated with MDRO colonization, may be ameliorated by pre-HCT FMT, even in the absence of intestinal MDRO decolonization. Further work is needed to explore this observed benefit.}, }
@article {pmid34507723, year = {2021}, author = {Pang, B and Jin, H and Liao, N and Li, J and Jiang, C and Shi, J}, title = {Vitamin A supplementation ameliorates ulcerative colitis in gut microbiota-dependent manner.}, journal = {Food research international (Ottawa, Ont.)}, volume = {148}, number = {}, pages = {110568}, doi = {10.1016/j.foodres.2021.110568}, pmid = {34507723}, issn = {1873-7145}, abstract = {Ulcerative colitis (UC), is a chronic relapsing inflammatory condition of the gastrointestinal track. The purpose of this study is to explore whether Vitamin A (VA) can treat UC and its mechanisms. A mouse model of UC was established using 3.0% (w/v) dextran sodium sulfate (DSS). VA was used to treat UC by intragastric administration of 5000 international unit (IU) retinyl acetate. Fecal microbiota transplantation (FMT) was also used to treat the UC model mice to verify the effect of influenced gut microbiota. The content of short-chain fatty acids (SCFAs) in cecal contents was quantitatively detected by gas chromatography and mass spectrometry. VA supplementation significantly ameliorated UC. 16S rRNA sequencing indicated that VA-treated mice exhibited much more abundant gut microbial diversity and flora composition. Targeted metabolomics analysis manifested the increased production of SCFAs in VA-treated mice. Gut microbiota depletion and FMT results confirmed the gut microbiota-dependent mechanism as that VA relieved UC via regulating gut microbiota: increase in SCFA-producing genera and decrease in UC-related genera. The restore of intestinal barrier and the inhibition of inflammation were also found to contribute to the amelioration of UC by VA. It was concluded that a VA supplement was enough to cause a significant change in gut microbiota and amelioration of UC.}, }
@article {pmid34500036, year = {2021}, author = {Kim, N and Ho Jeon, S and Gyoung Ju, I and Sung Gee, M and Do, J and Sook Oh, M and Kil Lee, J}, title = {Transplantation of gut microbiota derived from Alzheimer's disease mouse model impairs memory function and neurogenesis in C57BL/6 mice.}, journal = {Brain, behavior, and immunity}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bbi.2021.09.002}, pmid = {34500036}, issn = {1090-2139}, abstract = {Alzheimer's disease (AD) is a neurodegenerative disease that causes memory and cognitive decline. Although many studies have attempted to clarify the causes of AD occurrence, it is not clearly understood. Recently, the emerging role of the gut microbiota in neurodegenerative diseases, including AD, has received much attention. The gut microbiota composition of AD patients and AD mouse models is different from that of healthy controls, and these changes may affect the brain environment. However, the specific mechanisms by which gut microbiota that influence memory decline are currently unclear. In this study, we performed fecal microbiota transplantation (FMT) to clarify the role of 5xFAD mouse-derived microbiota in memory decline. We observed that FMT from 5xFAD mice into normal C57BL/6 mice (5xFAD-FMT) decreased adult hippocampal neurogenesis and brain-derived neurotrophic factor expression and increased p21 expression, resulting in memory impairment. Microglia in the hippocampus of the 5xFAD-FMT mice were activated, which caused the elevation of pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-1β). Moreover, we observed that pro-inflammatory cytokines increased in the colon and plasma of 5xFAD-FMT mice. The gut microbiota composition of the 5xFAD-FMT mice was different from that of the control mice or wild type-FMT mice. Collectively, 5xFAD mouse-derived microbiota decreased neurogenesis by increasing colonic inflammation, thereby contributing to memory loss. Our findings provide further evidence concerning the role of gut microbial dysbiosis in AD pathogenesis and suggest that targeting the gut microbiota may be a useful therapeutic strategy for the development of novel candidates for the treatment of AD.}, }
@article {pmid34495400, year = {2021}, author = {El Halabi, J and Palmer, N and Fox, K and Kohane, I and Farhat, MR}, title = {Fecal microbiota transplantation and Clostridioides difficile infection among privately insured patients in the United States.}, journal = {Journal of gastroenterology}, volume = {}, number = {}, pages = {}, pmid = {34495400}, issn = {1435-5922}, support = {T15LM007092/NH/NIH HHS/United States ; K01 ES026835/NH/NIH HHS/United States ; }, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) may be rising in severity in the US over the past decade and its treatment landscape is changing given the recent adoption of fecal microbiota transplantation (FMT) METHODS: We built a retrospective observational cohort using a database of a national care-plan containing medical claims of over 50 million individuals between 2008 and 2019. We used International Classification of Disease (ICD) and prescription data to identify patients with CDI. We estimated trends in disease burden and FMT use, and evaluated complications post FMT using a phenome-wide association approach.<br><br>RESULTS: We identified 38,396 patients with CDI; the median age was 60 years (IQR 45-74) and 60% were female (n = 23,374). The rate of CDI increased from 33.4 to 69.46 cases per 100,000 person-years between 2008 and 2015, and stabilized from 2015 to 2019 (increase of 4.77 cases per 100,000 person-years per year, 95% CI 3.55-5.98 prior to 2015 vs. 2.01 95% CI - 10.16 to 14.18 after 2015). Of the 7715 patients with recurrent CDI, 407 patients (5%) underwent FMT. Gastrointestinal complications were increased within 1 month post FMT (OR 99.60, p < 0.001). Sepsis was identified in two individuals (0.49% 95% CI 0.05-1.7%) within the first month post FMT. The risk of CDI recurrence significantly decreased post FMT compared with anti-CDI antibiotics in the multivariable model (raw-recurrence rate 9.8% vs 36%, aOR = 0.21, 95% CI 0.12-0.53, p < 0.001).<br><br>CONCLUSION: We show that FMT is strongly associated with a decrease in CDI recurrence compared with the usual care with generally mild complications for up to 2 years.}, }
@article {pmid34494666, year = {2021}, author = {Mjaess, G and Karam, A and Aoun, F and Albisinni, S and Roumeguère, T}, title = {Fecal microbiota transplantation for immunotherapy-resistant urological tumors: Is it time? An update of the recent literature.}, journal = {Cancer}, volume = {}, number = {}, pages = {}, doi = {10.1002/cncr.33893}, pmid = {34494666}, issn = {1097-0142}, }
@article {pmid34493333, year = {2021}, author = {Wu, Z and Huang, S and Li, T and Li, N and Han, D and Zhang, B and Xu, ZZ and Zhang, S and Pang, J and Wang, S and Zhang, G and Zhao, J and Wang, J}, title = {Gut microbiota from green tea polyphenol-dosed mice improves intestinal epithelial homeostasis and ameliorates experimental colitis.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {184}, pmid = {34493333}, issn = {2049-2618}, abstract = {BACKGROUND: Alteration of the gut microbiota may contribute to the development of inflammatory bowel disease (IBD). Epigallocatechin-3-gallate (EGCG), a major bioactive constituent of green tea, is known to be beneficial in IBD alleviation. However, it is unclear whether the gut microbiota exerts an effect when EGCG attenuates IBD.<br><br>RESULTS: We first explored the effect of oral or rectal EGCG delivery on the DSS-induced murine colitis. Our results revealed that anti-inflammatory effect and colonic barrier integrity were enhanced by oral, but not rectal, EGCG. We observed a distinct EGCG-mediated alteration in the gut microbiome by increasing Akkermansia abundance and butyrate production. Next, we demonstrated that the EGCG pre-supplementation induced similar beneficial outcomes to oral EGCG administration. Prophylactic EGCG attenuated colitis and significantly enriched short-chain fatty acids (SCFAs)-producing bacteria such as Akkermansia and SCFAs production in DSS-induced mice. To validate these discoveries, we performed fecal microbiota transplantation (FMT) and sterile fecal filtrate (SFF) to inoculate DSS-treated mice. Microbiota from EGCG-dosed mice alleviated the colitis over microbiota from control mice and SFF shown by superiorly anti-inflammatory effect and colonic barrier integrity, and also enriched bacteria such as Akkermansia and SCFAs. Collectively, the attenuation of colitis by oral EGCG suggests an intimate involvement of SCFAs-producing bacteria Akkermansia, and SCFAs, which was further demonstrated by prophylaxis and FMT.<br><br>CONCLUSIONS: This study provides the first data indicating that oral EGCG ameliorated the colonic inflammation in a gut microbiota-dependent manner. Our findings provide novel insights into EGCG-mediated remission of IBD and EGCG as a potential modulator for gut microbiota to prevent and treat IBD. Video Abstract.}, }
@article {pmid34490132, year = {2021}, author = {Jia, X and Xu, W and Zhang, L and Li, X and Wang, R and Wu, S}, title = {Impact of Gut Microbiota and Microbiota-Related Metabolites on Hyperlipidemia.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {634780}, doi = {10.3389/fcimb.2021.634780}, pmid = {34490132}, issn = {2235-2988}, abstract = {Hyperlipidemia, defined as the presence of excess fat or lipids in the blood, has been considered as a high-risk factor and key indicator of many metabolic diseases. The gut microbiota has been reported playing a vital role in regulating host lipid metabolism. The pathogenic role of gut microbiota in the development of hyperlipidemia has been revealed through fecal microbiota transplantation experiment to germ-free mice. The effector mechanism of microbiota-related metabolites such as bile acids, lipopolysaccharide, and short-chain fatty acids in the regulation of hyperlipidemia has been partially unveiled. Moreover, studies on gut-microbiota-targeted hyperlipidemia interventions, including the use of prebiotics, probiotics, fecal microbiota transplantation, and natural herbal medicines, also have shown their efficacy in the treatment of hyperlipidemia. In this review, we summarize the relationship between gut microbiota and hyperlipidemia, the impact of gut microbiota and microbiota-related metabolites on the development and progression of hyperlipidemia, and the potential therapeutic management of hyperlipidemia targeted at gut microbiota.}, }
@article {pmid34490119, year = {2021}, author = {Liu, X and Cheng, Y and Zang, D and Zhang, M and Li, X and Liu, D and Gao, B and Zhou, H and Sun, J and Han, X and Lin, M and Chen, J}, title = {The Role of Gut Microbiota in Lung Cancer: From Carcinogenesis to Immunotherapy.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {720842}, doi = {10.3389/fonc.2021.720842}, pmid = {34490119}, issn = {2234-943X}, abstract = {The influence of microbiota on host health and disease has attracted adequate attention, and gut microbiota components and microbiota-derived metabolites affect host immune homeostasis locally and systematically. Some studies have found that gut dysbiosis, disturbance of the structure and function of the gut microbiome, disrupts pulmonary immune homeostasis, thus leading to increased disease susceptibility; the gut-lung axis is the primary cross-talk for this communication. Gut dysbiosis is involved in carcinogenesis and the progression of lung cancer through genotoxicity, systemic inflammation, and defective immunosurveillance. In addition, the gut microbiome harbors the potential to be a novel biomarker for predicting sensitivity and adverse reactions to immunotherapy in patients with lung cancer. Probiotics and fecal microbiota transplantation (FMT) can enhance the efficacy and depress the toxicity of immune checkpoint inhibitors by regulating the gut microbiota. Although current studies have found that gut microbiota closely participates in the development and immunotherapy of lung cancer, the mechanisms require further investigation. Therefore, this review aims to discuss the underlying mechanisms of gut microbiota influencing carcinogenesis and immunotherapy in lung cancer and to provide new strategies for governing gut microbiota to enhance the prevention and treatment of lung cancer.}, }
@article {pmid34489956, year = {2021}, author = {Roberto, M and Carconi, C and Cerreti, M and Schipilliti, FM and Botticelli, A and Mazzuca, F and Marchetti, P}, title = {The Challenge of ICIs Resistance in Solid Tumours: Could Microbiota and Its Diversity Be Our Secret Weapon?.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {704942}, doi = {10.3389/fimmu.2021.704942}, pmid = {34489956}, issn = {1664-3224}, abstract = {The human microbiota and its functional interaction with the human body were recently returned to the spotlight of the scientific community. In light of the extensive implementation of newer and increasingly precise genome sequencing technologies, bioinformatics, and culturomic, we now have an extraordinary ability to study the microorganisms that live within the human body. Most of the recent studies only focused on the interaction between the intestinal microbiota and one other factor. Considering the complexity of gut microbiota and its role in the pathogenesis of numerous cancers, our aim was to investigate how microbiota is affected by intestinal microenvironment and how microenvironment alterations may influence the response to immune checkpoint inhibitors (ICIs). In this context, we show how diet is emerging as a fundamental determinant of microbiota's community structure and function. Particularly, we describe the role of certain dietary factors, as well as the use of probiotics, prebiotics, postbiotics, and antibiotics in modifying the human microbiota. The modulation of gut microbiota may be a secret weapon to potentiate the efficacy of immunotherapies. In addition, this review sheds new light on the possibility of administering fecal microbiota transplantation to modulate the gut microbiota in cancer treatment. These concepts and how these findings can be translated into the therapeutic response to cancer immunotherapies will be presented.}, }
@article {pmid33493503, year = {2021}, author = {Margolis, KG and Cryan, JF and Mayer, EA}, title = {The Microbiota-Gut-Brain Axis: From Motility to Mood.}, journal = {Gastroenterology}, volume = {160}, number = {5}, pages = {1486-1501}, doi = {10.1053/j.gastro.2020.10.066}, pmid = {33493503}, issn = {1528-0012}, support = {R01 NS015547/NS/NINDS NIH HHS/United States ; R01 DK048351/DK/NIDDK NIH HHS/United States ; }, mesh = {*Affect ; Animals ; Bacteria/*growth &amp; development/metabolism ; Brain/metabolism/*physiopathology ; Central Nervous System Diseases/*microbiology/physiopathology/psychology/therapy ; Dysbiosis ; Fecal Microbiota Transplantation ; Gastrointestinal Diseases/*microbiology/physiopathology/psychology/therapy ; *Gastrointestinal Microbiome ; *Gastrointestinal Motility ; Humans ; Intestines/*innervation/*microbiology ; }, abstract = {The gut-brain axis plays an important role in maintaining homeostasis. Many intrinsic and extrinsic factors influence signaling along this axis, modulating the function of both the enteric and central nervous systems. More recently the role of the microbiome as an important factor in modulating gut-brain signaling has emerged and the concept of a microbiota-gut-brain axis has been established. In this review, we highlight the role of this axis in modulating enteric and central nervous system function and how this may impact disorders such as irritable bowel syndrome and disorders of mood and affect. We examine the overlapping biological constructs that underpin these disorders with a special emphasis on the neurotransmitter serotonin, which plays a key role in both the gastrointestinal tract and in the brain. Overall, it is clear that although animal studies have shown much promise, more progress is necessary before these findings can be translated for diagnostic and therapeutic benefit in patient populations.}, }
@article {pmid33436437, year = {2021}, author = {Amenyogbe, N and Dimitriu, P and Smolen, KK and Brown, EM and Shannon, CP and Tebbutt, SJ and Cooper, PJ and Marchant, A and Goetghebuer, T and Esser, M and Finlay, BB and Kollmann, TR and Mohn, WW}, title = {Biogeography of the Relationship between the Child Gut Microbiome and Innate Immune System.}, journal = {mBio}, volume = {12}, number = {1}, pages = {}, pmid = {33436437}, issn = {2150-7511}, support = {/WT_/Wellcome Trust/United Kingdom ; PJT-148781//CIHR/Canada ; CMF-108029//CIHR/Canada ; 088862/Z/09/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Bacteria/*classification ; Biodiversity ; Canada ; Child, Preschool ; Cytokines/metabolism ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*immunology/physiology ; Germ-Free Life ; Host Microbial Interactions/*immunology ; Humans ; *Immune System ; Immunity, Innate ; Infant ; Male ; Phylogeography ; Toll-Like Receptor 2 ; }, abstract = {The gut microbiome is a well-recognized modulator of host immunity, and its compositions differ between geographically separated human populations. Systemic innate immune responses to microbial derivatives also differ between geographically distinct human populations. However, the potential role of the microbiome in mediating geographically varied immune responses is unexplored. We here applied 16S amplicon sequencing to profile the stool microbiome and, in parallel, measured whole-blood innate immune cytokine responses to several pattern recognition receptor (PRR) agonists among 2-year-old children across biogeographically diverse settings. Microbiomes differed mainly between high- and low-resource environments and were not strongly associated with other demographic factors. We found strong correlations between responses to Toll-like receptor 2 (TLR2) and relative abundances of Bacteroides and Prevotella populations, shared among Canadian and Ecuadorean children. Additional correlations between responses to TLR2 and bacterial populations were specific to individual geographic cohorts. As a proof of concept, we gavaged germfree mice with human donor stools and found murine splenocyte responses to TLR stimulation were consistent with responses of the corresponding human donor populations. This study identified differences in immune responses correlating to gut microbiomes across biogeographically diverse settings and evaluated biological plausibility using a mouse model. This insight paves the way to guide optimization of population-specific interventions aimed to improve child health outcomes.IMPORTANCE Both the gut microbiome and innate immunity are known to differ across biogeographically diverse human populations. The gut microbiome has been shown to directly influence systemic immunity in animal models. With this, modulation of the gut microbiome represents an attractive avenue to improve child health outcomes associated with altered immunity using population-specific approaches. However, there are very scarce data available to determine which members of the gut microbiome are associated with specific immune responses and how these differ around the world, creating a substantial barrier to rationally designing such interventions. This study addressed this knowledge gap by identifying relationships between distinct bacterial taxa and cytokine responses to specific microbial agonists across highly diverse settings. Furthermore, we provide evidence that immunomodulatory effects of region-specific stool microbiomes can be partially recapitulated in germfree mice. This is an important contribution toward improving global child health by targeting the gut microbiome.}, }
@article {pmid33310084, year = {2021}, author = {Galipeau, HJ and Caminero, A and Turpin, W and Bermudez-Brito, M and Santiago, A and Libertucci, J and Constante, M and Raygoza Garay, JA and Rueda, G and Armstrong, S and Clarizio, A and Smith, MI and Surette, MG and Bercik, P and ,  and Croitoru, K and Verdu, EF}, title = {Novel Fecal Biomarkers That Precede Clinical Diagnosis of Ulcerative Colitis.}, journal = {Gastroenterology}, volume = {160}, number = {5}, pages = {1532-1545}, doi = {10.1053/j.gastro.2020.12.004}, pmid = {33310084}, issn = {1528-0012}, support = {1715-000-001//CIHR/Canada ; 143253//CIHR/Canada ; }, mesh = {Adolescent ; Adult ; Animals ; Bacteria/drug effects/*enzymology/genetics ; Bacterial Proteins/genetics/*metabolism ; Biomarkers/metabolism ; Case-Control Studies ; Child ; Colitis, Ulcerative/diagnosis/drug therapy/*microbiology ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome/drug effects ; Germ-Free Life ; Humans ; Male ; Metagenome ; Metagenomics ; Mice, Inbred C57BL ; Peptide Hydrolases/genetics/*metabolism ; Predictive Value of Tests ; Prospective Studies ; Protease Inhibitors/therapeutic use ; Proteolysis ; Reproducibility of Results ; Ribotyping ; Young Adult ; }, abstract = {BACKGROUND &amp; AIMS: Altered gut microbiota composition and function have been associated with inflammatory bowel diseases, including ulcerative colitis (UC), but the causality and mechanisms remain unknown.<br><br>METHODS: We applied 16S ribosomal RNA gene sequencing, shotgun metagenomic sequencing, in vitro functional assays, and gnotobiotic colonizations to define the microbial composition and function in fecal samples obtained from a cohort of healthy individuals at risk for inflammatory bowel diseases (pre-UC) who later developed UC (post-UC) and matched healthy control individuals (HCs).<br><br>RESULTS: Microbiota composition of post-UC samples was different from HC and pre-UC samples; however, functional analysis showed increased fecal proteolytic and elastase activity before UC onset. Metagenomics identified more than 22,000 gene families that were significantly different between HC, pre-UC, and post-UC samples. Of these, 237 related to proteases and peptidases, suggesting a bacterial component to the pre-UC proteolytic signature. Elastase activity inversely correlated with the relative abundance of Adlercreutzia and other potentially beneficial taxa and directly correlated with known proteolytic taxa, such as Bacteroides vulgatus. High elastase activity was confirmed in Bacteroides isolates from fecal samples. The bacterial contribution and functional significance of the proteolytic signature were investigated in germ-free adult mice and in dams colonized with HC, pre-UC, or post-UC microbiota. Mice colonized with or born from pre-UC-colonized dams developed higher fecal proteolytic activity and an inflammatory immune tone compared with HC-colonized mice.<br><br>CONCLUSIONS: We have identified increased fecal proteolytic activity that precedes the clinical diagnosis of UC and associates with gut microbiota changes. This proteolytic signature may constitute a noninvasive biomarker of inflammation to monitor at-risk populations that can be targeted therapeutically with antiproteases.}, }
@article {pmid32916306, year = {2020}, author = {Hartstra, AV and Schüppel, V and Imangaliyev, S and Schrantee, A and Prodan, A and Collard, D and Levin, E and Dallinga-Thie, G and Ackermans, MT and Winkelmeijer, M and Havik, SR and Metwaly, A and Lagkouvardos, I and Nier, A and Bergheim, I and Heikenwalder, M and Dunkel, A and Nederveen, AJ and Liebisch, G and Mancano, G and Claus, SP and Benítez-Páez, A and la Fleur, SE and Bergman, JJ and Gerdes, V and Sanz, Y and Booij, J and Kemper, E and Groen, AK and Serlie, MJ and Haller, D and Nieuwdorp, M}, title = {Infusion of donor feces affects the gut-brain axis in humans with metabolic syndrome.}, journal = {Molecular metabolism}, volume = {42}, number = {}, pages = {101076}, pmid = {32916306}, issn = {2212-8778}, mesh = {Aged ; Butyrates/pharmacology ; Cerebral Cortex/metabolism ; Dopamine Plasma Membrane Transport Proteins/metabolism ; Double-Blind Method ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Gastrointestinal Microbiome ; Humans ; Insulin/metabolism ; Insulin Resistance/physiology ; Male ; Metabolic Syndrome/metabolism/*microbiology/*therapy ; Microbiota ; Middle Aged ; Obesity/metabolism ; Serotonin Plasma Membrane Transport Proteins/metabolism ; }, abstract = {OBJECTIVE: Increasing evidence indicates that intestinal microbiota play a role in diverse metabolic processes via intestinal butyrate production. Human bariatric surgery data suggest that the gut-brain axis is also involved in this process, but the underlying mechanisms remain unknown.<br><br>METHODS: We compared the effect of fecal microbiota transfer (FMT) from post-Roux-en-Y gastric bypass (RYGB) donors vs oral butyrate supplementation on (123I-FP-CIT-determined) brain dopamine transporter (DAT) and serotonin transporter (SERT) binding as well as stable isotope-determined insulin sensitivity at baseline and after 4 weeks in 24 male and female treatment-naïve metabolic syndrome subjects. Plasma metabolites and fecal microbiota were also determined at these time points.<br><br>RESULTS: We observed an increase in brain DAT after donor FMT compared to oral butyrate that reduced this binding. However, no effect on body weight and insulin sensitivity was demonstrated after post-RYGB donor feces transfer in humans with metabolic syndrome. Increases in fecal levels of Bacteroides uniformis were significantly associated with an increase in DAT, whereas increases in Prevotella spp. showed an inverse association. Changes in the plasma metabolites glycine, betaine, methionine, and lysine (associated with the S-adenosylmethionine cycle) were also associated with altered striatal DAT expression.<br><br>CONCLUSIONS: Although more and larger studies are needed, our data suggest a potential gut microbiota-driven modulation of brain dopamine and serotonin transporters in human subjects with obese metabolic syndrome. These data also suggest the presence of a gut-brain axis in humans that can be modulated.<br><br>NTR REGISTRATION: 4488.}, }
@article {pmid34487914, year = {2021}, author = {Opoku-Acheampong, I and McLaud, T and Anderson, OS}, title = {The Implications of Fecal Microbiota Transplantation in Dietetics Practice to Prevent and Treat Chronic Disease.}, journal = {Journal of the Academy of Nutrition and Dietetics}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jand.2021.08.112}, pmid = {34487914}, issn = {2212-2672}, }
@article {pmid34486891, year = {2021}, author = {Sanlier, N and Kocabas, Ş}, title = {The effect of probiotic, prebiotic and gut microbiota on ASD: A review and future perspectives.}, journal = {Critical reviews in food science and nutrition}, volume = {}, number = {}, pages = {1-12}, doi = {10.1080/10408398.2021.1973957}, pmid = {34486891}, issn = {1549-7852}, abstract = {Autism spectrum disorder is a serious neurodevelopmental disease that affects social communication and behavior, characterized by an increasingly common immune mechanism and various complications in the gastrointestinal system. Symptoms of autism can generally vary according to the genetic background of the individuals, the environment in which they live. The microbiota of individuals with autism is also different from healthy individuals. Recently, probiotics, prebiotic, fecal microbiota transplantation, diet therapy, etc. options have come to the fore. Cofactors are even more important at this stage. Since it is related to the gut microbiota, immune mechanism, gastrointestinal system, attention has been drawn to the relationship between dysbiosis, autism in the intestine. The component of the gut microbiota in individuals with autism has been linked with gastrointestinal symptoms that develop with autism severity. However, the role of the microbiota in diagnosis, follow-up, treatment is not clear yet, and its two-way relationship with the nervous system makes it difficult to establish a cause-effect relationship. Nutritional cofactors required in neurotransmitter synthesis and enzyme activation must be regularly and adequately taken to maximize brain functions in autistic individuals. Therefore, this study was conducted to investigate the cause-effect relationship of ASD with microbiota and brain-gut axis, probiotic-prebiotic use.}, }
@article {pmid34484158, year = {2021}, author = {Yang, Y and Li, X and Yang, Y and Shoaie, S and Zhang, C and Ji, B and Wei, Y}, title = {Advances in the Relationships Between Cow's Milk Protein Allergy and Gut Microbiota in Infants.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {716667}, doi = {10.3389/fmicb.2021.716667}, pmid = {34484158}, issn = {1664-302X}, abstract = {Cow's milk protein allergy (CMPA) is an immune response to cow's milk proteins, which is one of the most common food allergies in infants and young children. It is estimated that 2-3% of infants and young children have CMPA. The diet, gut microbiota, and their interactions are believed to be involved in the alterations of mucosal immune tolerance, which might lead to the development of CMPA and other food allergies. In this review, the potential molecular mechanisms of CMPA, including omics technologies used for analyzing microbiota, impacts of early microbial exposures on CMPA development, and microbiota-host interactions, are summarized. The probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and other modulation strategies for gut microbiota and the potential application of microbiota-based design of diets for the CMPA treatment are also discussed. This review not only summarizes the current studies about the interactions of CMPA with gut microbiota but also gives insights into the possible CMPA treatment strategies by modulating gut microbiota, which might help in improving the life quality of CMPA patients in the future.}, }
@article {pmid34484126, year = {2021}, author = {Jo, S and Fang, S}, title = {Therapeutic Strategies for Diabetes: Immune Modulation in Pancreatic β Cells.}, journal = {Frontiers in endocrinology}, volume = {12}, number = {}, pages = {716692}, doi = {10.3389/fendo.2021.716692}, pmid = {34484126}, issn = {1664-2392}, abstract = {Increased incidence of type I and type II diabetes has been prevailed worldwide. Though the pathogenesis of molecular mechanisms remains still unclear, there are solid evidence that disturbed immune homeostasis leads to pancreatic β cell failure. Currently, autoimmunity and uncontrolled inflammatory signaling pathways have been considered the major factors in the pathogenesis of diabetes. Many components of immune system have been reported to implicate pancreatic β cell failure, including helper T cells, cytotoxic T cells, regulatory T cells and gut microbiota. Immune modulation of those components using small molecules and antibodies, and fecal microbiota transplantation are undergoing in many clinical trials for the treatment of type I and type II diabetes. In this review we will discuss the basis of molecular pathogenesis focusing on the disturbed immune homeostasis in type I and type II diabetes, leading to pancreatic β cell destruction. Finally, we will introduce current therapeutic strategies and clinical trials by modulation of immune system for the treatment of type I and type II diabetes patients.}, }
@article {pmid34480200, year = {2021}, author = {Wang, N and Ma, S and Fu, L}, title = {Gut Microbiota Dysbiosis as One Cause of Osteoporosis by Impairing Intestinal Barrier Function.}, journal = {Calcified tissue international}, volume = {}, number = {}, pages = {}, pmid = {34480200}, issn = {1432-0827}, support = {82172456//National Natural Science Foundation of China/ ; JYJC201809//the Cross-disciplinary Fund Projects of the Ninth People's Hospital/ ; 20210407//Seeds Fund of Engineering Research Center of Digital Medicine of the Ministry of Education/ ; 2017ZZ01023//Shanghai Clinical Medical Center/ ; }, abstract = {Gut microbiota (GM) dysbiosis is closely related to several metabolic diseases such as hypertension, obesity, and Alzheimer's disease. However, little is known about the causal relationship between GM dysbiosis and osteoporosis. In our work, 32 3-month-old female SD rats were randomly divided into two groups: the fecal microbiota transplantation (FMT) group and the control group. The supernatant of feces from senile osteoporotic rats was transplanted to the FMT group and the same amount of sterile saline was given to the control rats. After 12 and 24 weeks, all rats were sacrificed, and the serum, bone, fecal feces, and intestine tissue were collected for the subsequent analysis. The osteocalcin (OC), CTX, and P1NP of the FMT group increased significantly at 12 and 24 weeks compared with the control group (P < 0.05). Furthermore, the BV, BV/TV, Tb.N, and Tb.Th decreased significantly in the FMT group (P < 0.05). The alpha diversity (ACE, Chao) of the FMT group was higher than the control at 24 weeks (P < 0.05). The beta diversity was close between the FMT rats and the donor rats. In addition, GM from donor rats changed the GM composition and function of the FMT rats, which was similar to that of the donor rats at 24 weeks. The impaired intestinal structure and the decreased expression of occludin, claudin, and ZO-1 were found in FMT rats. In conclusion, GM dysbiosis by transferring the feces from senile osteoporotic rats to young rats could induce osteoporosis. The changed GM and the impaired intestinal barrier contributed to the pathogenesis of osteoporosis.}, }
@article {pmid34478286, year = {2021}, author = {Chen, S and Wu, X and Tang, S and Yin, J and Song, Z and He, X and Yin, Y}, title = {Eugenol Alleviates Dextran Sulfate Sodium-Induced Colitis Independent of Intestinal Microbiota in Mice.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.1c00917}, pmid = {34478286}, issn = {1520-5118}, abstract = {The present study investigated the effect of eugenol (EUG) on dextran sulfate sodium (DSS)-induced colitis and explored the underlying mechanisms. C57BL/6 mice were intragastrically administered normal saline or EUG (20 mg/kg body weight) for 17 days, and colitis was induced by using 3% DSS from day 7. The results showed that EUG increased the body weight and reduced the disease activity index score and colon pathological scores in DSS-treated mice (P < 0.05). Further, EUG preserved the proinflammatory cytokines (interleukin (IL)-6, -12, -21, and -23), lowered (P < 0.05) colonic malondialdehyde (MDA), uncoupling protein 2 (UCP2) expression and p65 phosphorylation, and activated (P < 0.05) colonic kelch-like ECH-associated protein 1 and nuclear factor (erythroid-derived 2)-like 2 expressions but did not affect the intestinal microbiota in DSS-treated mice. Furthermore, EUG ameliorated colitis in antibiotic-treated mice, while fecal microbiota transplantation from EUG preadministered mice failed to ameliorate colitis. In conclusion, EUG could alleviate colitis by attenuating colonic inflammation and oxidative stress independent of intestinal microbiota.}, }
@article {pmid34455517, year = {2021}, author = {Li, JJ and Zhu, M and Kashyap, PC and Chia, N and Tran, NH and McWilliams, RR and Bekaii-Saab, TS and Ma, WW}, title = {The role of microbiome in pancreatic cancer.}, journal = {Cancer metastasis reviews}, volume = {}, number = {}, pages = {}, pmid = {34455517}, issn = {1573-7233}, abstract = {Recent studies of the human microbiome have offered new insights into how the microbiome can impact cancer development and treatment. Specifically, in pancreatic ductal adenocarcinoma (PDAC), the microbiota has been shown to modulate PDAC risk, contribute to tumorigenesis, impact the tumor microenvironment, and alter treatment response. These findings provide rationale for further investigations into leveraging the microbiome to develop new strategies to diagnose and treat PDAC patients. There is growing evidence that microbiome analyses have the potential to become easily performed, non-invasive diagnostic, prognostic, and predictive biomarkers in pancreatic cancer. More excitingly, there is now emerging interest in developing interventions based on the modulation of microbiota. Fecal microbiota transplantation, probiotics, dietary changes, and antibiotics are all potential strategies to augment the efficacy of current therapeutics and reduce toxicities. While there are still challenges to overcome, this is a rapidly growing field that holds promise for translation into clinical practice and provides a new approach to improving patient outcomes.}, }
@article {pmid32484770, year = {2020}, author = {Zatorski, H and Nakov, R}, title = {Faecal Microbiota Transplantation in Inflammatory Bowel Disease: Current Concepts and Future Challenges.}, journal = {Current drug targets}, volume = {21}, number = {14}, pages = {1440-1447}, doi = {10.2174/1389450121666200602125507}, pmid = {32484770}, issn = {1873-5592}, support = {502-03/1-156-04/502-14-339//Medical University of Lodz/ ; }, mesh = {Animals ; Dysbiosis/therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Feces/microbiology ; Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/microbiology/*therapy ; Randomized Controlled Trials as Topic ; }, abstract = {Dysbiosis has been repeatedly observed in inflammatory bowel disease (IBD) and is now recognized as an essential factor in the gut inflammatory process. IBD is a significant burden to health-care systems, mainly due to treatment-related costs. Available treatments have several limitations: up to 30% of patients are primary non-responders, and between 10 and 20% lose response per year, requiring a dose-escalation or a switch to another biologic. Hence, the current IBD treatment is not sufficient, and there is an urgent need to introduce new therapies in the management of these patients. Recently, the correction of dysbiosis has become an attractive approach from a therapeutic point of view. Faecal microbiota transplantation (FMT) appears as a reliable and potentially beneficial therapy in IBD patients. There is developing data that FMT for mild-to-moderately active UC is a safe and efficient therapy for the induction of remission. However, the current studies have different designs and have a short follow up, which makes clinical interpretation significantly difficult. There is a need for RCTs with a well-defined study cohort using FMT for the therapy of CD patients. The location, behavior, and severity of the disease should be taken into account. The goal of this manuscript is to review the data currently available on FMT and IBD, to explain FMT principles and methodology in IBD patients and to discuss some unresolved issues.}, }
@article {pmid34473644, year = {2021}, author = {Sui, G and Jia, L and Quan, D and Zhao, N and Yang, G}, title = {Activation of the gut microbiota-kynurenine-liver axis contributes to the development of nonalcoholic hepatic steatosis in nondiabetic adults.}, journal = {Aging}, volume = {13}, number = {undefined}, pages = {}, doi = {10.18632/aging.203460}, pmid = {34473644}, issn = {1945-4589}, abstract = {The contribution of gut-liver signaling to the development of non-alcoholic hepatic steatosis (NHS) in non-diabetic adults remains unclear. We therefore performed comprehensive 16S ribosomal RNA sequencing and fecal metabolomics analyses in 32 controls and 59 non-diabetic adults with NHS and performed fecal microbiota transplantation into germ-free mice using controls and NHS patients as donors. Compared to controls, the abundance of the genera Collinsella and Acinetobacter were higher, while that of Lachnospira was lower, in NHS subjects. Fecal metabolomics analysis showed decreased L-tryptophan levels and increased abundance of the tryptophan metabolite kynurenine in individuals with NHS. Correlation analysis showed that kynurenine levels positively associated with the abundance of Collinsella and Acinetobacter. ROC analysis demonstrated that the combination of tryptophan and kynurenine could discriminate NHS patients from controls with good statistical power [P < 0.05; AUC = 0.833 (95% CI, 0.747 to 0.918)]. Supporting a key role of dysbiotic gut microbiota in NHS development, incipient hepatic steatosis and increased kynurenine levels were observed in GF mice colonized with samples from NHS patients. These results indicate that enhanced kynurenine production resulting from altered gut microbiota composition contributes to NHS in nondiabetic adults and suggest the relevance of tryptophan metabolites as diagnostic biomarkers.}, }
@article {pmid34473374, year = {2021}, author = {Liu, C and Wang, YL and Yang, YY and Zhang, NP and Niu, C and Shen, XZ and Wu, J}, title = {Novel approaches to intervene gut microbiota in the treatment of chronic liver diseases.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {35}, number = {10}, pages = {e21871}, doi = {10.1096/fj.202100939R}, pmid = {34473374}, issn = {1530-6860}, support = {#2016YFE0107400//National Key Research and Development Program of China/ ; 81572356//Natural Science Foundation of China/ ; 81871997//Natural Science Foundation of China/ ; 82170624//Natural Science Foundation of China/ ; }, abstract = {Recent investigations of gut microbiota have contributed to understanding of the critical role of microbial community in pathophysiology. Dysbiosis not only causes disturbance directly to the gastrointestinal tract but also affects the liver through gut-liver axis. Various types of dysbiosis have been documented in alcoholic liver disease (ALD), nonalcoholic fatty liver disease, autoimmune hepatitis (AIH), primary sclerosing cholangitis, and may be crucial for the initiation, progression, or deterioration to end-stage liver disease. A few microbial species have been identified as the causal factors leading to these chronic illnesses that either do not have clear etiologies or lack effective treatment. Notably, cytolysin-producing Enterococcus faecalis, Klebsiella pneumoniae and Enterococcus gallinarum were defined for ALD, NASH, and AIH, respectively. These groundbreaking discoveries drive a rapid development in innovative therapeutics, such as fecal microbial transplantation and implementation of specific bacteriophages in addition to prebiotics, probiotics, or synbiotics for intervention of dysbiosis. Although most emerging interventions are in preclinical development or early clinical trials, a better delineation of specific dysbiosis in these disorders at metabolic, immunogenic, or molecular levels in establishing particular causal effects aids in modulating or correcting the microbial community which is the part of daily life for human being.}, }
@article {pmid34469716, year = {2021}, author = {Sun, WL and Li, XY and Dou, HY and Wang, XD and Li, JD and Shen, L and Ji, HF}, title = {Myricetin supplementation decreases hepatic lipid synthesis and inflammation by modulating gut microbiota.}, journal = {Cell reports}, volume = {36}, number = {9}, pages = {109641}, doi = {10.1016/j.celrep.2021.109641}, pmid = {34469716}, issn = {2211-1247}, abstract = {The relationship between poor in vivo bioavailability and effective pharmacological activity are not yet fully clarified for many flavonoids. The analysis of flavonoids-induced alterations in the gut microbiota represents a promising approach to provide useful clues to elucidate the mechanism of action. Here, we investigate the effect of myricetin supplementation on high-fat-diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) in rats and explore the associations with the gut microbiota through high-throughput analyses. The 12-week myricetin supplementation and fecal microbiota transplantation outcomes suggest that myricetin significantly slows the development of NAFLD. Meanwhile, the anti-NAFLD effects of myricetin are associated with the modulation of the gut microbiota composition. Myricetin reduces hepatic lipid synthesis and inflammation through modulations in fecal butyric-acid-related gut microbiota and protection of the gut barrier function. This study may facilitate the elucidation of the action mechanism of flavonoids with low bioavailability.}, }
@article {pmid34463082, year = {2021}, author = {Bonetto, S and Fagoonee, S and Battaglia, E and Grassini, M and Saracco, GM and Pellicano, R}, title = {Recent advances in the treatment of irritable bowel syndrome.}, journal = {Polish archives of internal medicine}, volume = {131}, number = {7-8}, pages = {709-715}, doi = {10.20452/pamw.16067}, pmid = {34463082}, issn = {1897-9483}, abstract = {Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder which presents with abdominal pain and altered bowel habits. It affects about 20% of the general population, mainly women, and has a considerable impact on the quality of life and health care costs. Four different entities of IBS have been identified: IBS with constipation (IBS‑ C), IBS with diarrhea (IBS D), IBS with a mixed pattern of constipation and diarrhea, and unclassified IBS. Although the precise pathogenesis of IBS remains unclear, its multifactorial nature is evident and includes environmental and host factors. Management of patients with this disease is challenging and a personalized approach is required. A strong, reassuring physician‑ patient relationship is crucial, followed by patient education, dietary advice, and stress reduction. For nonresponding patients, the therapeutic approach may include nonpharmacological therapies and / or pharmacotherapy. The choice of pharmacological treatment is based on the predominant symptom and a prespecified time point should be planned for effectiveness evaluation and dose adjustment. In patients with IBS‑ D, the therapeutic options include mainly antibiotics, such as rifaximin, peripheral opioid agonists, mixed opioid agonists / antagonists, bile acid sequestrants, and antagonists of serotonin 5‑ hydroxytryptamine type 3 receptors. Bulking agents and osmotic laxatives represent the first line therapy for IBS‑ C, while lubiprostone and linaclotide should be reserved for difficult to treat patients. The involvement of gastrointestinal microbiota constitutes a fascinating field of exploration as it offers the potential to be modulated by the use of probiotics, prebiotics, synbiotics as well as fecal microbiota transplantation. This review offers an updated overview on the recent advances in the treatment of IBS.}, }
@article {pmid34462225, year = {2021}, author = {Abu El-Haija, M and Ye, Y and Chu, Y and Herz, H and Linden, B and Shahi, SK and Zarei, K and Mangalam, AK and Mcelroy, SJ and Mokadem, M}, title = {Toll-like receptor 4 and myeloid differentiation factor 88 are required for gastric bypass-induced metabolic effects.}, journal = {Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.soard.2021.07.019}, pmid = {34462225}, issn = {1878-7533}, abstract = {BACKGROUND: Toll-like receptor 4 (TLR4) has been suggested as one of the forefront cross-communicators between the intestinal bacteria and the host to regulate inflammatory signals and energy homeostasis. High-fat diet-induced inflammation is mediated by changes in gut microbiota and requires a functional TLR-4, the deficiency of which renders mice resistant to diet-induced obesity and its associated metabolic dysfunction. Furthermore, gut microbiota was suggested to play a key role in the beneficial effects of Roux-en-Y gastric bypass (RYGB), a commonly performed bariatric procedure.<br><br>OBJECTIVES: To explore whether TLR4, myeloid differentiation factor 8 (MyD88; 1 of its key downstream signaling regulators) and gut microbiota play an integrative role in RYGB-induced metabolic outcomes.<br><br>SETTING: Animal- based study.<br><br>METHOD: We performed RYGB in TLR4 and MyD88 knock-out (KO) mice and used fecal microbiota transplant (FMT) from RYGB-operated animals to these genetic mouse models to address our questions.<br><br>RESULTS: We demonstrate that RYGB reduces TLR4 expression explicitly in the small and large intestine of C57Blc/6J mice. We also show that TLR4 KO mice have an attenuated glucoregulatory response to RYGB. In addition, we reveal that MyD88 KO mice fail to respond to all RYGB-induced metabolic effects. Finally, fecal microbiota transplant from RYGB-operated mice into TLR4 KO and MyD88 KO naïve recipients fails to induce a metabolic phenotype similar to that of the donors, as it does in wild-type recipients.<br><br>CONCLUSION: TLR4 and MyD88 are required for RYGB-induced metabolic response that is likely mediated by gut microbiome.}, }
@article {pmid34461052, year = {2021}, author = {Yang, J and Wei, H and Zhou, Y and Szeto, CH and Li, C and Lin, Y and Coker, OO and Lau, HCH and Chan, AW and Sung, JJ and Yu, J}, title = {High-Fat Diet Promotes Colorectal Tumorigenesis through Modulating Gut Microbiota and Metabolites.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2021.08.041}, pmid = {34461052}, issn = {1528-0012}, abstract = {BACKGROUND &amp; AIMS: Dietary fat intake is associated with increased risk of colorectal cancer (CRC). We examined the role of high-fat diet (HFD) in driving CRC through modulating gut microbiota and metabolites.<br><br>METHODS: HFD or control diet (CD) was fed to mice littermates in CRC mouse models of azoxymethane (AOM) model and Apcmin/+ model, with or without antibiotics cocktail treatment. Germ-free mice for fecal microbiota transplantation were utilized for validation. Gut microbiota and metabolites were respectively detected by metagenomic sequencing and high-performance liquid chromatography-mass spectrometry. Gut barrier function was determined by lipopolysaccharides (LPS) level and transmission electron microscopy.<br><br>RESULTS: HFD promoted colorectal tumorigenesis in both AOM-treated mice and Apcmin/+ mice compared with CD-fed mice. Gut microbiota depletion by antibiotics attenuated colon tumor formation in HFD-fed mice. A significant shift of gut microbiota composition with increased pathogenic bacteria Alistipes sp. Marseille-P5997 and Alistipes sp. 5CPEGH6, and depleted probiotic Parabacteroides distasonis, along with impaired gut barrier function was exhibited in HFD-fed mice. Moreover, HFD-modulated gut microbiota promotes colorectal tumorigenesis in AOM-treated germ-free mice, indicating gut microbiota was essential in HFD-associated colorectal tumorigenesis. Gut metabolites alteration including elevated lysophosphatidic acid (LPA) which was confirmed to promote CRC cell proliferation and impair cell junction was also observed in HFD-fed mice. Moreover, transfer of stools from HFD-fed mice to germ-free mice without interference increased colonic cell proliferation, impaired gut barrier function and induced oncogenic genes expression.<br><br>CONCLUSION: HFD drives colorectal tumorigenesis through inducing gut microbial dysbiosis, metabolomic dysregulation with elevated LPA, and gut barrier dysfunction in mice.}, }
@article {pmid34458158, year = {2021}, author = {Zhong, HJ and Zeng, HL and Cai, YL and Zhuang, YP and Liou, YL and Wu, Q and He, XX}, title = {Washed Microbiota Transplantation Lowers Blood Pressure in Patients With Hypertension.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {679624}, doi = {10.3389/fcimb.2021.679624}, pmid = {34458158}, issn = {2235-2988}, abstract = {Background: Although transplantation of the fecal microbiota from normotensive donors has been shown to have an antihypertensive effect in hypertensive animal models, its effect on blood pressure in patients with hypertension is unclear. This study aimed to assess the effect of washed microbiota transplantation (WMT) from normotensive donors on blood pressure regulation in hypertensive patients.<br><br>Methods: The clinical data of consecutive patients treated with washed microbiota transplantation (WMT) were collected retrospectively. The blood pressures of hypertensive patients before and after WMT were compared. The factors influencing the antihypertensive effect of WMT in hypertensive patients and fecal microbial composition of donors and hypertensive patients were also analyzed.<br><br>Results: WMT exhibited an antihypertensive effect on blood pressure: the blood pressure at hospital discharge was significantly lower than that at hospital admission (change in systolic blood pressure: -5.09 ± 15.51, P = 0.009; change in diastolic blood pressure: -7.74 ± 10.42, P < 0.001). Hypertensive patients who underwent WMT via the lower gastrointestinal tract (β = -8.308, standard error = 3.856, P = 0.036) and those not taking antihypertensive drugs (β = -8.969, standard error = 4.256, P = 0.040) had a greater decrease in systolic blood pressure, and hypertensive patients not taking antihypertensive drugs also had a greater decrease in diastolic blood pressure (β = -8.637, standard error = 2.861, P = 0.004). After WMT, the Shannon Diversity Index was higher in six of eight hypertensive patients and the microbial composition of post-WMT samples tended to be closer to that of donor samples.<br><br>Conclusion: WMT had a blood pressure-lowering effect in hypertensive patients, especially in those who underwent WMT via the lower gastrointestinal tract and in those not taking antihypertensive drugs. Therefore, modulation of the gut microbiota by WMT may offer a novel approach for hypertension treatment.}, }
@article {pmid34453966, year = {2021}, author = {Bloom, P and Tapper, EB and Young, VB and Lok, AS}, title = {Microbiome Therapeutics for Hepatic Encephalopathy.}, journal = {Journal of hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhep.2021.08.004}, pmid = {34453966}, issn = {1600-0641}, abstract = {Hepatic encephalopathy (HE) is a complication of cirrhosis characterized by neuropsychiatric and motor dysfunction. Microbiota-host interactions have an important role in HE pathogenesis. Therapies targeting microbial community composition and function have been explored for the treatment of HE. Prebiotics, probiotics and fecal microbiota transplant (FMT) have aimed to increase the abundance of potentially beneficial taxa, while antibiotics have aimed to decrease the abundance of potentially harmful taxa. Other microbiome therapeutics, including postbiotics and absorbents, have been used to target microbial products. Microbiome-targeted therapies for HE have had some success, notably lactulose and rifaximin, with early promise for probiotics and FMT. Microbiome therapeutics face several challenges in HE, including the resilience of the microbiome to sustainable change and unpredictable clinical outcomes from microbiota alterations. Future work in this space should focus on rigorous trial design, microbiome therapy selection, and a personalized approach to HE.}, }
@article {pmid34452466, year = {2021}, author = {Desselberger, U}, title = {Significance of the Gut Microbiome for Viral Diarrheal and Extra-Intestinal Diseases.}, journal = {Viruses}, volume = {13}, number = {8}, pages = {}, doi = {10.3390/v13081601}, pmid = {34452466}, issn = {1999-4915}, abstract = {The composition of the mammalian gut microbiome is very important for the health and disease of the host. Significant correlations of particular gut microbiota with host immune responsiveness and various infectious and noninfectious host conditions, such as chronic enteric infections, type 2 diabetes, obesity, asthma, and neurological diseases, have been uncovered. Recently, research has moved on to exploring the causalities of such relationships. The metabolites of gut microbiota and those of the host are considered in a 'holobiontic' way. It turns out that the host's diet is a major determinant of the composition of the gut microbiome and its metabolites. Animal models of bacterial and viral intestinal infections have been developed to explore the interrelationships of diet, gut microbiome, and health/disease phenotypes of the host. Dietary fibers can act as prebiotics, and certain bacterial species support the host's wellbeing as probiotics. In cases of Clostridioides difficile-associated antibiotic-resistant chronic diarrhea, transplantation of fecal microbiomes has sometimes cured the disease. Future research will concentrate on the definition of microbial/host/diet interrelationships which will inform rationales for improving host conditions, in particular in relation to optimization of immune responses to childhood vaccines.}, }
@article {pmid34450312, year = {2021}, author = {Socała, K and Doboszewska, U and Szopa, A and Serefko, A and Włodarczyk, M and Zielińska, A and Poleszak, E and Fichna, J and Wlaź, P}, title = {The role of microbiota-gut-brain axis in neuropsychiatric and neurological disorders.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {105840}, doi = {10.1016/j.phrs.2021.105840}, pmid = {34450312}, issn = {1096-1186}, abstract = {Emerging evidence indicates that the gut microbiota play a crucial role in the bidirectional communication between the gut and the brain suggesting that gut microbes may shape neural development, modulate neurotransmission and affect behavior, and thereby contribute to the pathogenesis and/or progression of many neurodevelopmental, neuropsychiatric, and neurological conditions. This review summarizes recent data on the role of microbiota-gut-brain axis in the pathophysiology of neuropsychiatric and neurological disorders including depression, anxiety, schizophrenia, autism spectrum disorders, Parkinson's disease, migraine, and epilepsy. Also, the involvement of microbiota in gut disorders co-existing with neuropsychiatric conditions is highlighted. We discuss data from both in vivo preclinical experiments and clinical reports including: (1) studies in germ-free animals, (2) studies exploring the gut microbiota composition in animal models of diseases or in humans, (3) studies evaluating the effects of probiotics, prebiotics or antibiotics treatment as well as (4) the effects of fecal microbiota transplantation.}, }
@article {pmid34449321, year = {2021}, author = {Duan, L and An, X and Zhang, Y and Jin,  and Zhao, S and Zhou, R and Duan, Y and Zhang, Y and Liu, X and Lian, F}, title = {Gut microbiota as the critical correlation of polycystic ovary syndrome and type 2 diabetes mellitus.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {142}, number = {}, pages = {112094}, doi = {10.1016/j.biopha.2021.112094}, pmid = {34449321}, issn = {1950-6007}, abstract = {Gut microbiota forms a symbiotic relationship with the host and maintains the ecological balance of the internal and external environment of the human body. However, dysbiosis of the gut microbiota and immune deficiency, as well as environmental changes, can destroy the host-microbial balance, leading to the occurrence of a variety of diseases, such as polycystic ovary syndrome (PCOS), type 2 diabetes mellitus (T2DM), and obesity. Meanwhile, diseases can also affect gut microbiota, forming a vicious cycle. The role of the intestinal microbiota in different diseases have been proven by several studies; however, as a common target of PCOS and T2DM, there are few reports on the treatment of different diseases through the regulation of intestinal microbiota as the critical correlation. This review analyzed the common mechanisms of intestinal microbiota in PCOS and T2DM, including the dysbiosis of gut microbiota, endotoxemia, short-chain fatty acids, biotransformation of bile acids, and synthesis of amino acid in regulating insulin resistance, obesity, chronic inflammation, and mitochondrial dysfunction. The possible therapeutic effects of probiotics and/or prebiotics, fecal microbiota transplantation, bariatric surgery, dietary intervention, drug treatment, and other treatments targeted at regulating intestinal microbiota were also elucidated.}, }
@article {pmid34447287, year = {2021}, author = {Zhang, L and Chu, J and Hao, W and Zhang, J and Li, H and Yang, C and Yang, J and Chen, X and Wang, H}, title = {Gut Microbiota and Type 2 Diabetes Mellitus: Association, Mechanism, and Translational Applications.}, journal = {Mediators of inflammation}, volume = {2021}, number = {}, pages = {5110276}, doi = {10.1155/2021/5110276}, pmid = {34447287}, issn = {1466-1861}, abstract = {Gut microbiota has attracted widespread attention due to its crucial role in disease pathophysiology, including type 2 diabetes mellitus (T2DM). Metabolites and bacterial components of gut microbiota affect the initiation and progression of T2DM by regulating inflammation, immunity, and metabolism. Short-chain fatty acids, secondary bile acid, imidazole propionate, branched-chain amino acids, and lipopolysaccharide are the main molecules related to T2DM. Many studies have investigated the role of gut microbiota in T2DM, particularly those butyrate-producing bacteria. Increasing evidence has demonstrated that fecal microbiota transplantation and probiotic capsules are useful strategies in preventing diabetes. In this review, we aim to elucidate the complex association between gut microbiota and T2DM inflammation, metabolism, and immune disorders, the underlying mechanisms, and translational applications of gut microbiota. This review will provide novel insight into developing individualized therapy for T2DM patients based on gut microbiota immunometabolism.}, }
@article {pmid34439657, year = {2021}, author = {Abuaish, S and Al-Otaibi, NM and Abujamel, TS and Alzahrani, SA and Alotaibi, SM and AlShawakir, YA and Aabed, K and El-Ansary, A}, title = {Fecal Transplant and Bifidobacterium Treatments Modulate Gut Clostridium Bacteria and Rescue Social Impairment and Hippocampal BDNF Expression in a Rodent Model of Autism.}, journal = {Brain sciences}, volume = {11}, number = {8}, pages = {}, doi = {10.3390/brainsci11081038}, pmid = {34439657}, issn = {2076-3425}, support = {RGP-1441-0027//Deanship of Scientific Research, Princess Nourah bint Abdulrahman University, the Research Group Program/ ; }, abstract = {Autism is associated with gastrointestinal dysfunction and gut microbiota dysbiosis, including an overall increase in Clostridium. Modulation of the gut microbiota is suggested to improve autistic symptoms. In this study, we explored the implementation of two different interventions that target the microbiota in a rodent model of autism and their effects on social behavior: the levels of different fecal Clostridium spp., and hippocampal transcript levels. Autism was induced in young Sprague Dawley male rats using oral gavage of propionic acid (PPA) for three days, while controls received saline. PPA-treated animals were divided to receive either saline, fecal transplant from healthy donor rats, or Bifidobacterium for 22 days, while controls continued to receive saline. We found that PPA attenuated social interaction in animals, which was rescued by the two interventions. PPA-treated animals had a significantly increased abundance of fecal C. perfringens with a concomitant decrease in Clostridium cluster IV, and exhibited high hippocampal Bdnf expression compared to controls. Fecal microbiota transplantation or Bifidobacterium treatment restored the balance of fecal Clostridium spp. and normalized the level of Bdnf expression. These findings highlight the involvement of the gut-brain axis in the etiology of autism and propose possible interventions in a preclinical model of autism.}, }
@article {pmid32414814, year = {2021}, author = {Camilleri, M}, title = {FMT in IBS: a call for caution.}, journal = {Gut}, volume = {70}, number = {2}, pages = {431}, doi = {10.1136/gutjnl-2020-321529}, pmid = {32414814}, issn = {1468-3288}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome/therapy ; }, }
@article {pmid34430117, year = {2021}, author = {Nandwana, V and Debbarma, S}, title = {Fecal Microbiota Transplantation: A Microbiome Modulation Technique for Alzheimer's Disease.}, journal = {Cureus}, volume = {13}, number = {7}, pages = {e16503}, doi = {10.7759/cureus.16503}, pmid = {34430117}, issn = {2168-8184}, abstract = {Alzheimer's disease (AD) is the most common form of dementia and the fifth leading cause of death among the elderly. AD involves parts of the brain that can lead to progressive memory loss and impaired language skills and cognitive thinking, affecting one's ability to carry out daily activities. Aging, bad dietary habits, family history, as well as altered gut microbiota composition may play a role in the pathogenesis of AD. Although the association between the imbalance of gut microbiota and AD is still difficult to determine, it has been suggested that dysbiosis can lead to the increased secretion of lipopolysaccharides and amyloid, which may impair the permeability of the intestine and the blood-brain barrier. Moreover, it can progress the process of neuroinflammation, amyloid-beta formation, and ultimately neuronal death. Microbiota-targeted interventions such as personalized diet, probiotics, or fecal microbiota transplantation (FMT) might represent a potential therapeutic option for AD. This review article discusses the procedure of FMT and its possible side effects on the recipient's body. In addition, we review the role of FMT in the context of its application in various nervous system-related disorders (AD, Parkinson's disease, multiple sclerosis).}, }
@article {pmid34428426, year = {2021}, author = {Jiao, X and Pei, X and Lu, D and Qi, D and Huang, S and He, S and Li, Z}, title = {Microbial reconstitution improves aging-driven lacrimal gland circadian dysfunction.}, journal = {The American journal of pathology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajpath.2021.08.006}, pmid = {34428426}, issn = {1525-2191}, abstract = {The lacrimal glands are highly susceptible to aging and exhibit age-related structural and functional alterations. However, the mechanisms by which aging affects the lacrimal glands are not well-established. Here, this study explores the crosstalk between the aging process, gut microbiota, and circadian rhythm in age-associated lacrimal gland dysfunction. C57BL/6J mice were divided into young, old, and fecal microbiota transplant (FMT)-treated old groups. The gut bacterial community diversity was analyzed by 16S rRNA sequencing. Exorbital lacrimal glands (ELGs) were collected at 3-hour intervals over a 24-hour circadian cycle, and total RNA was subjected to high-throughput sequencing. Rhythmic transcriptional data were analyzed using the Jonckheere-Terpstra-Kendall algorithm and bioinformatics analysis technology. Immunostaining was used to identify lymphocytic infiltration, lipid deposition, and nerve innervation in the ELGs. Compared with young mice, old mice underwent a significant gut microbial community shift. In the old ELGs, the rhythmically transcriptomic profile was significantly reprogrammed over a 24-hour cycle. After intervention with serial FMT from young donors for one month, the gut microbial community of the old mice was rejuvenated. Most alterations in rhythmic transcriptomic profiling were improved. Furthermore, the chronic inflammation, lipid deposition, and aberrant neural response of the aging lacrimal glands were significantly reduced. Thus, the reconstitution of age-associated gut dysbiosis with FMTs from young donors improves aging-driven lacrimal gland circadian dysfunction.}, }
@article {pmid34426641, year = {2021}, author = {Samuelson, DR and Gu, M and Shellito, JE and Molina, PE and Taylor, CM and Luo, M and Welsh, DA}, title = {Pulmonary immune cell trafficking promotes host defense against alcohol-associated Klebsiella pneumonia.}, journal = {Communications biology}, volume = {4}, number = {1}, pages = {997}, pmid = {34426641}, issn = {2399-3642}, support = {R00-AA026336//U.S. Department of Health &amp; Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAAA)/ ; K99-AA026336//U.S. Department of Health &amp; Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAAA)/ ; P60-AA009803//U.S. Department of Health &amp; Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAAA)/ ; R21-AA027199//U.S. Department of Health &amp; Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAAA)/ ; U54-GM104940//U.S. Department of Health &amp; Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; }, abstract = {The intestinal microbiota generates many different metabolites which are critical for the regulation of host signaling pathways. In fact, a wide-range of diseases are associated with increased levels of local or systemic microbe-derived metabolites. In contrast, certain bacterial metabolites, such as tryptophan metabolites, are known to contribute to both local and systemic homeostasis. Chronic alcohol consumption is accompanied by alterations to intestinal microbial communities, and their functional capacities. However, little is known about the role of alcohol-associated dysbiosis on host defense against bacterial pneumonia. Our previous work using fecal transplantation demonstrated that alcohol-associated intestinal dysbiosis, independent of ethanol consumption, increased susceptibility to Klebsiella pneumonia. Here, we demonstrate that intestinal microbiota treatments mitigate the increased risk of alcohol-associated pneumonia. Treatment with the microbial metabolite indole or with probiotics reduced pulmonary and extrapulmonary bacterial burden, restored immune responses, and improved cellular trafficking required for host defense. Protective effects were, in part, mediated by aryl hydrocarbon receptors (AhR), as inhibition of AhR diminished the protective effects. Thus, alcohol appears to impair the production/processing of tryptophan catabolites resulting in immune dysregulation and impaired cellular trafficking. These data support microbiota therapeutics as novel strategies to mitigate the increased risk for alcohol-associated bacterial pneumonia.}, }
@article {pmid32701590, year = {2020}, author = {, }, title = {Nanjing consensus on methodology of washed microbiota transplantation.}, journal = {Chinese medical journal}, volume = {133}, number = {19}, pages = {2330-2332}, pmid = {32701590}, issn = {2542-5641}, mesh = {Consensus ; Feces ; *Microbiota ; }, }
@article {pmid34424831, year = {2021}, author = {de Wouters d'Oplinter, A and Rastelli, M and Van Hul, M and Delzenne, NM and Cani, PD and Everard, A}, title = {Gut microbes participate in food preference alterations during obesity.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1959242}, doi = {10.1080/19490976.2021.1959242}, pmid = {34424831}, issn = {1949-0984}, abstract = {Hypothalamic regulations of food intake are altered during obesity. The dopaminergic mesocorticolimbic system, responsible for the hedonic response to food intake, is also affected. Gut microbes are other key players involved in obesity. Therefore, we investigated whether the gut microbiota plays a causal role in hedonic food intake alterations contributing to obesity. We transferred fecal material from lean or diet-induced obese mice into recipient mice and evaluated the hedonic food intake using a food preference test comparing the intake of control and palatable diets (HFHS, High-Fat High-Sucrose) in donor and recipient mice. Obese mice ate 58% less HFHS during the food preference test (p < 0.0001) than the lean donors, suggesting a dysregulation of the hedonic food intake during obesity. Strikingly, the reduction of the pleasure induced by eating during obesity was transferable through gut microbiota transplantation since obese gut microbiota recipient mice exhibited similar reduction in HFHS intake during the food preference test (40% reduction as compared to lean gut microbiota recipient mice, p < 0.01). This effect was associated with a consistent trend in modifications of dopaminergic markers expression in the striatum. We also pinpointed a highly positive correlation between HFHS intake and Parabacteroides (p < 0.0001), which could represent a potential actor involved in hedonic feeding probably through the gut-to-brain axis. We further demonstrated the key roles played by gut microbes in this paradigm since depletion of gut microbiota using broad-spectrum antibiotics also altered HFHS intake during food preference test in lean mice. In conclusion, we discovered that gut microbes regulate hedonic aspects of food intake. Our data demonstrate that gut microbiota modifications associated with obesity participate in dysregulations of the reward and hedonic components of the food intake. These data provide evidence that gut microbes could be an interesting therapeutic target to tackle hedonic disorders related to obesity.}, }
@article {pmid34424357, year = {2021}, author = {Schiereck, T and Yeldan, S and Kranz, J and Schneidewind, L and Wagenlehner, F and Wieters, I and Vehreschild, MJGT and Otto, T and Barski, D}, title = {[Urinary bladder microbiome analysis and probiotic treatment options for women with recurrent urinary tract infections].}, journal = {Der Urologe. Ausg. A}, volume = {}, number = {}, pages = {}, pmid = {34424357}, issn = {1433-0563}, abstract = {Novel preventive measures and therapeutic approaches are needed to reduce the frequency of recurrent urinary tract infections (rUTI) and the associated emergence of multidrug-resistant uropathogens. The aim of this review is to systematically present the available evidence on the urinary bladder microbiome of healthy women and those with rUTIs. In addition, relevant studies on the efficacy of probiotics in rUTIs are presented in a structured manner. This will provide an overview on the current state of research and an outlook on treatment strategies beyond the usual antimicrobial options.}, }
@article {pmid34419965, year = {2021}, author = {Kullberg, RFJ and Wiersinga, WJ and Haak, BW}, title = {Gut microbiota and sepsis: from pathogenesis to novel treatments.}, journal = {Current opinion in gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MOG.0000000000000781}, pmid = {34419965}, issn = {1531-7056}, abstract = {PURPOSE OF REVIEW: This review summarizes recent progress in our understanding of the role of the gut microbiota in sepsis pathogenesis and outlines the potential role of microbiota-targeted therapies.<br><br>RECENT FINDINGS: The composition of the gut microbiome is profoundly distorted during sepsis, with a loss of commensal bacteria and an overgrowth of potential pathogenic micro-organisms. These alterations also extend to nonbacterial intestinal inhabitants. Disruptions of these intestinal communities are associated with both an increased susceptibility to develop sepsis, as well as a higher risk of adverse outcomes. Preclinical studies have characterized the effects of several microbiota-derived metabolites (such as D-lactate, butyrate, and deoxycholic acid) on enhancing the host immune response during critical illness. Microbiota-targeted therapies (e.g. probiotics or fecal microbiota transplantation) might be of benefit, but can also be associated with increased risks of bloodstream infections.<br><br>SUMMARY: Emerging evidence display an important role of gut micro-organisms (including bacteria, fungi, eukaryotic viruses, and bacteriophages) and their derived metabolites in both the susceptibility to, as well as outcomes of sepsis. Despite recent progress in the mechanistic understanding of microbiota-mediated protection, clinical breakthroughs in the development of microbiota-based prognostic tools or therapies are thus far lacking in the field of sepsis.}, }
@article {pmid34419770, year = {2021}, author = {Cheraghmakani, H and Rezai, MS and Valadan, R and Rahimzadeh, G and Moradi, M and Jahanfekr, V and Moosazadeh, M and Tabrizi, N}, title = {Ciprofloxacin for treatment of drug-resistant epilepsy.}, journal = {Epilepsy research}, volume = {176}, number = {}, pages = {106742}, doi = {10.1016/j.eplepsyres.2021.106742}, pmid = {34419770}, issn = {1872-6844}, abstract = {PURPOSE: To investigate the efficacy of short-term treatment with ciprofloxacin in alteration of gut microbiota pattern and reduction of seizure frequency in adult patients with drug-resistant epilepsy.<br><br>METHODS: In a prospective study, we investigated the effect of a 5-day course of treatment with ciprofloxacin on gut microbiota pattern and seizure frequency of 23 adults with drug-resistant epilepsy. Fecal samples were collected before and after treatment and were analyzed for microbial load and species. Changes in seizure frequency were registered for 12 weeks. Responders were defined as patients who experienced ≥50 % seizure reduction in comparison to baseline. Outcome measures were specified as alteration in fecal microbial burden in days 5-7 and responder rate in 4th and 12th weeks.<br><br>RESULTS: The mean baseline frequency of seizures was5.6 ±7.7 per week. All patients were on polytherapy with a mean of 3 ± 1.2 anti-seizure medications. Microbial analysis showed a considerable increase in Bacteroidetes/Firmicutes ratio after treatment. Seizure frequency significantly decreased at the end of first week and the therapeutic effect continued to week 12 (P < 0.001). The responder rate at 4th and 12th weeks were 69.6 % and 73.9 % respectively with a more prominent response in patients with symptomatic generalized epilepsy (P:0.06).<br><br>CONCLUSION: Alteration of abnormal gut microbiota pattern by methods such as short-course antibiotic therapy, prescription of probiotics and fecal microbiota transplant might be effective in treatment of drug-resistant epilepsy.}, }
@article {pmid34416751, year = {2021}, author = {Cao, M and Peng, Y and Lu, Y and Zou, Z and Chen, J and Bottino, R and Knoll, M and Zhang, H and Lin, S and Pu, Z and Sun, L and Fang, Z and Qiu, C and Dai, Y and Cai, Z and Mou, L}, title = {Controls of Hyperglycemia Improves Dysregulated Microbiota in Diabetic Mice.}, journal = {Transplantation}, volume = {105}, number = {9}, pages = {1980-1988}, pmid = {34416751}, issn = {1534-6080}, abstract = {BACKGROUND: Type 1 diabetes (T1DM) is a chronic autoimmune disease characterized by T-cell-mediated destruction of insulin-producing beta cells. Evidence shows that patients with T1DM and mice used in specific diabetic models both exhibit changes in their intestinal microbiota and dysregulated microbiota contributes to the pathogenesis of T1DM. Islet transplantation (Tx) is poised to play an important role in the treatment of T1DM. However, whether treatment of T1DM with islet Tx can rescue dysregulated microbiota remains unclear.<br><br>METHODS: In this study, we induced diabetic C57BL/6 mice with streptozotocin. Then treatment with either insulin administration, or homogenic or allogenic islet Tx was performed to the diabetic mice. Total DNA was isolated from fecal pellets and high-throughput 16S rRNA sequencing was used to investigate intestinal microbiota composition.<br><br>RESULTS: The overall microbial diversity was comparable between control (nonstreptozotocin treated) and diabetic mice. Our results showed the ratio of the Bacteroidetes: Firmicutes between nondiabetic and diabetic mice was significant different. Treatment with islet Tx or insulin partially corrects the dysregulated bacterial composition. At the genus level, Bacteroides, Odoribacter, and Alistipes were associated with the progression and treatment efficacy of the disease, which may be used as a biomarker to predict curative effect of treatment for patients with T1DM.<br><br>CONCLUSIONS: Collectively, our results indicate that diabetic mice show changed microbiota composition and that treatment with insulin and islet Tx can partially correct the dysregulated microbiota.}, }
@article {pmid34416387, year = {2021}, author = {An, L and Wuri, J and Zheng, Z and Li, W and Yan, T}, title = {Microbiota modulate Doxorubicin induced cardiotoxicity.}, journal = {European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences}, volume = {}, number = {}, pages = {105977}, doi = {10.1016/j.ejps.2021.105977}, pmid = {34416387}, issn = {1879-0720}, abstract = {Chemotherapy has several adverse effects to patients, some of which are life-threatening. We hypothesized that Doxorubicin induced microbiome imbalance and intestinal damage may contribute to Doxorubicin induced cardiac dysfunction. Male adult (2-3 months) C57BL/6 mice were administered 3mg/kg, 5mg/kg, 7.5mg/kg,15mg/kg, 20mg/kg doses of Doxorubicin. Echocardiography was performed at 7 and 14 days after Doxorubicin administration. 16S rRNA amplicon sequencing was used to characterize microbiome changes. Fecal microbiota transplantation (FMT) was performed to evaluate the role of the microbiota on Doxorubicin induced cardiac dysfunction. Doxorubicin dose dependently increases mortality rate and induces cardiac dysfunction. 5mg/kg-Doxorubicin significantly induces decreased left ventricular ejection fraction (LVEF) and fraction shortening (FS) as well as increased cardiac fibrosis, inflammation and oxidative stress respond without increasing mortality. 5mg/kg-Doxorubicin induces significant decreased colorectum length, increased loss of goblet cells, numbers of ulcers and infiltration of lymphocyte clusters and decreased tight junction protein ZO-1, as well as increased plasma endotoxin level measured by ELISA assay. 16S rRNA microbiota analysis shows that Doxorubicin-induced microbiota dysbiosis with decreased community richness compared with normal control mice. FMT to Doxorubicin-5mg treated mice significantly improved cardiac function by increasing LVEF and FS as well as decreased perivascular and interstitial fibrosis; increased colorectum length, decreased the loss of goblet cells,infiltration of lymphocyte clusters,the number of ulcers and plasma endotoxin level; improved microbiota composition, function and diversity with increased abundance of Alloprevotella, Prevotellaceae_UCG-001 and Rikenellaceae_RC9_gut_group.We find that normal fecal transplantation improves cardiac function, decreases gut damage and alter microbiota composition induced by Doxorubicin. The microbiota appears to contribute to heart-gut interaction.}, }
@article {pmid34415656, year = {2021}, author = {Chen, B and Huang, H and Pan, CQ}, title = {The Role of Gut Microbiota in Hepatitis B Disease Progression and Treatment.}, journal = {Journal of viral hepatitis}, volume = {}, number = {}, pages = {}, doi = {10.1111/jvh.13595}, pmid = {34415656}, issn = {1365-2893}, abstract = {Current therapeutic interventions can only suppress HBV replication or reduce complications without a cure. Therefore, further development of new treatment methods is critical for the global eradication of HBV. Accumulating evidence suggests that the liver and gut share an interconnected relationship referred to as the "Gut-Liver Axis", where exchanges happen bi-directionally. The gut itself is the host to a unique microbiota profile which has metabolic, immunological, neurological, and nutritional functions. Gut microbiota is not only constantly intersecting with the liver but also associated with hepatic injury when dysbiosis occurs. In recent years, there has been increased interest in gut microbiota and its implications on liver disease treatment. Progress has been made in understanding the complex relationship between chronic hepatitis B (CHB) and gut microbiota. New investigative techniques such as colony-free sequencing enabled new perspectives into this field. Mouse models and human studies revealed that HBV infection is associated with significant alteration of gut microbiota, which differ depending on the stage of CHB disease progression. Different mechanisms of the hepatic injury from gut microbiota dysbiosis have also been proposed based on findings of increased intestinal permeability to toxins, disruption of normal bacterial metabolism, and colonization of the gut by oral microbiota. New treatment methods targeting gut microbiota in CHB, such as probiotics and fecal microbiota transplant, have also gained promising results in recent years. The current review recapitulated the most recent investigations into the relationship between gut microbiota and CHB to provide research directions towards the new therapeutic target of CHB.}, }
@article {pmid33350360, year = {2021}, author = {Holster, S and Repsilber, D and Geng, D and Hyötyläinen, T and Salonen, A and Lindqvist, CM and Rajan, SK and de Vos, WM and Brummer, RJ and König, J}, title = {Correlations between microbiota and metabolites after faecal microbiota transfer in irritable bowel syndrome.}, journal = {Beneficial microbes}, volume = {12}, number = {1}, pages = {17-30}, doi = {10.3920/BM2020.0010}, pmid = {33350360}, issn = {1876-2891}, mesh = {Bacteria/classification/genetics/isolation &amp; purification/*metabolism ; *Fecal Microbiota Transplantation ; Feces/chemistry/microbiology ; Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/*metabolism/microbiology/*therapy ; Phylogeny ; Treatment Outcome ; }, abstract = {Faecal microbiota transfer (FMT) consists of the infusion of donor faecal material into the intestine of a patient with the aim to restore a disturbed gut microbiota. In this study, it was investigated whether FMT has an effect on faecal microbial composition, its functional capacity, faecal metabolite profiles and their interactions in 16 irritable bowel syndrome (IBS) patients. Faecal samples from eight different time points before and until six months after allogenic FMT (faecal material from a healthy donor) as well as autologous FMT (own faecal material) were analysed by 16S RNA gene amplicon sequencing and gas chromatography coupled to mass spectrometry (GS-MS). The results showed that the allogenic FMT resulted in alterations in the microbial composition that were detectable up to six months, whereas after autologous FMT this was not the case. Similar results were found for the functional profiles, which were predicted from the phylogenetic sequencing data. While both allogenic FMT as well as autologous FMT did not have an effect on the faecal metabolites measured in this study, correlations between the microbial composition and the metabolites showed that the microbe-metabolite interactions seemed to be disrupted after allogenic FMT compared to autologous FMT. This shows that FMT can lead to altered interactions between the gut microbiota and its metabolites in IBS patients. Further research should investigate if and how this affects efficacy of FMT treatments.}, }
@article {pmid34410652, year = {2021}, author = {Zhu, Z and Kaiser, T and Staley, C}, title = {Antibiotic Conditioning and Single Gavage Allows Stable Engraftment of Human Microbiota in Mice.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2327}, number = {}, pages = {281-291}, pmid = {34410652}, issn = {1940-6029}, abstract = {Mice transplanted with human microbiota are essential tools for studying the role of microbiota in health and disease, striving for the development of microbiota-modulating therapeutics. Traditionally, germ-free mice have been the principal option for establishing human microbiota-associated (HMA) mouse models, leading to significant insights into the composition and function of the human microbiota. However, there are limitations in using germ-free mice as recipients of human microbiota, including considerable resource allocation to establish and maintain the model and incomplete development of their immune system and physiological functions. Thus, antibiotic-treated, non-germ-free mice have been developed as an alternative to satisfy the growing demand for an accessible HMA mouse model. Several methods have been described for creating "humanized" mice. These protocols vary in their key components, mainly antibiotic conditioning and frequency of oral gavage. To address this practical challenge and formulate a simple and repeatable protocol, we established a HMA mouse model with antibiotic-treated conventional and specific-pathogen free (SPF) C57BL/6J mice, revealing that a single oral gavage allows stable engraftment of the human microbiota. In this chapter, we present our simple protocol for antibiotic conditioning to prepare mice for stable engraftment of human gut microbiota.}, }
@article {pmid34409064, year = {2021}, author = {Yu, X and Zuo, T}, title = {Editorial: Food Additives, Cooking and Processing: Impact on the Microbiome.}, journal = {Frontiers in nutrition}, volume = {8}, number = {}, pages = {731040}, doi = {10.3389/fnut.2021.731040}, pmid = {34409064}, issn = {2296-861X}, }
@article {pmid34408753, year = {2021}, author = {Varricchi, G and Poto, R and Ianiro, G and Punziano, A and Marone, G and Gasbarrini, A and Spadaro, G}, title = {Gut Microbiome and Common Variable Immunodeficiency: Few Certainties and Many Outstanding Questions.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {712915}, doi = {10.3389/fimmu.2021.712915}, pmid = {34408753}, issn = {1664-3224}, abstract = {Common variable immunodeficiency (CVID) is the most common symptomatic primary antibody immunodeficiency, characterized by reduced serum levels of IgG, IgA, and/or IgM. The vast majority of CVID patients have polygenic inheritance. Immune dysfunction in CVID can frequently involve the gastrointestinal tract and lung. Few studies have started to investigate the gut microbiota profile in CVID patients. Overall, the results suggest that in CVID patients there is a reduction of alpha and beta diversity compared to controls. In addition, these patients can exhibit increased plasma levels of lipopolysaccharide (LPS) and markers (sCD14 and sCD25) of systemic immune cell activation. CVID patients with enteropathy exhibit decreased IgA expression in duodenal tissue. Mouse models for CVID unsatisfactorily recapitulate the polygenic causes of human CVID. The molecular pathways by which gut microbiota contribute to systemic inflammation and possibly tumorigenesis in CVID patients remain poorly understood. Several fundamental questions concerning the relationships between gut microbiota and the development of chronic inflammatory conditions, autoimmune disorders or cancer in CVID patients remain unanswered. Moreover, it is unknown whether it is possible to modify the microbiome and the outcome of CVID patients through specific therapeutic interventions.}, }
@article {pmid34000958, year = {2021}, author = {Madsen, AMA and Halkjær, SI and Christensen, AH and Günther, S and Browne, PD and Kallemose, T and Hansen, LH and Petersen, AM}, title = {The effect of faecal microbiota transplantation on abdominal pain, stool frequency, and stool form in patients with moderate-to-severe irritable bowel syndrome: results from a randomised, double-blind, placebo-controlled study.}, journal = {Scandinavian journal of gastroenterology}, volume = {56}, number = {7}, pages = {761-769}, doi = {10.1080/00365521.2021.1915375}, pmid = {34000958}, issn = {1502-7708}, mesh = {Abdominal Pain/etiology/therapy ; Adult ; Double-Blind Method ; Fecal Microbiota Transplantation ; Feces ; Humans ; *Irritable Bowel Syndrome/therapy ; Treatment Outcome ; }, abstract = {BACKGROUND: Irritable bowel syndrome (IBS) is associated with intestinal dysbiosis. Therefore, faecal microbiota transplantation (FMT) has been hypothesised to have a positive effect in patients with IBS. In this study, we analysed previously unexamined data from our randomised, double-blind, placebo-controlled study (trial registration number NCT02788071). The objective was to evaluate the effect of FMT on abdominal pain, stool frequency, and stool form.<br><br>METHOD: The study included 52 adult patients with moderate-to-severe IBS assigned randomly to treatment with FMT capsules or placebo capsules (1:1) for 12 days. The patients were followed for a total of six months, during which they kept a daily symptom diary tracking their abdominal pain on a scale from 0-10 and their bowel movements using the Bristol Stool Form Scale (BSFS). Diary data were not collected before treatment start.<br><br>RESULTS: A statistically significant improvement in stool frequency was found in the FMT group from during treatment to post-treatment and 1 month. No statistically significant differences were found between groups at any time during the study for any of abdominal pain, stool frequency, and stool form (as measured by weighted stool score).<br><br>CONCLUSION: In this analysis of results from a randomised, double-blind, placebo-controlled study, we found no clinically beneficial effect of FMT on abdominal pain, stool frequency, or stool form. However, since the current literature on the potential role of FMT in treating IBS shows conflicting results, further studies are required. To assess treatment efficacy, we recommend future studies to include daily symptom diaries both before and after treatment intervention.}, }
@article {pmid32181906, year = {2020}, author = {Leong, KSW and O'Sullivan, JM and Derraik, JGB and Cutfield, WS}, title = {Gut microbiome transfer-Finding the perfect fit.}, journal = {Clinical endocrinology}, volume = {93}, number = {1}, pages = {3-10}, doi = {10.1111/cen.14183}, pmid = {32181906}, issn = {1365-2265}, mesh = {*Clostridium Infections ; *Diabetes Mellitus, Type 2 ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {Gut microbiome transfer (GMT; also referred to as faecal microbiota transplantation or FMT) has been propelled from fringe therapy to mainstream science as a highly effective treatment for recurrent Clostridioides difficile infection. As a result, there has been great interest in the potential efficacy and safety of GMT in treating other medical conditions, for example inflammatory bowel disease, and more recently as a novel therapy for obesity and metabolic diseases. For these chronic conditions, the results from clinical trials have been mixed. Further, specifically in obesity and metabolic diseases, there are limited available data, with only a few published studies with a small number of participants and short duration of follow-up. Therefore, this review aims to explore the human, microbial and formulation factors that may affect the success of GMT. This includes various aspects in the preparation and administration of GMT, such as stool processing, modes of delivery, pretreatment with antibiotics and/or bowel lavage, frequency of GMT and possible use of precision bacteriotherapy. In addition, we examine the potential use of GMT in obesity, type 2 diabetes and metabolic diseases based on current available literature, highlighting some recent advances in GMT research in this area, as well as potential adverse effects after GMT therapy.}, }
@article {pmid34403877, year = {2021}, author = {Chen, L and Kan, J and Zheng, N and Li, B and Hong, Y and Yan, J and Tao, X and Wu, G and Ma, J and Zhu, W and Sheng, L and Chen, L and Li, B and Zhong, J and Du, J and Li, H}, title = {A botanical dietary supplement from white peony and licorice attenuates nonalcoholic fatty liver disease by modulating gut microbiota and reducing inflammation.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {91}, number = {}, pages = {153693}, doi = {10.1016/j.phymed.2021.153693}, pmid = {34403877}, issn = {1618-095X}, abstract = {BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is an obesity-related metabolic disease that is highly associated with gut dysbiosis and inflammation. A botanical dietary supplement, mainly containing an herbal pair of white peony root and licorice as well as grape seeds and broccoli extracts (WLT), exerts auxiliary protection against chemical liver injury. However, it is unclear whether WLT protects against the development of NAFLD induced by a high energy diet.<br><br>PURPOSE: To investigate the protective role of WLT against NAFLD development induced by a high-fat and high-sucrose (HFHS) diet and its mechanism of action.<br><br>METHODS: We investigated the anti-NAFLD effects of WLT on a HFHS diet-induced NAFLD C57BL/6J mouse model by detecting the hepatic triglyceride (TG) level, performing histological examination of the liver tissue, and evaluating glucose tolerance and systemic inflammation. Then, we analyzed the impact of WLT on gut microbiota by 16S rRNA gene sequencing, followed by fecal microbiota transplantation. Furthermore, we performed hepatic transcriptomic analysis of mice with or without WLT treatment using the RNA sequencing approach.<br><br>RESULTS: Our results showed that WLT supplement attenuated body weight gain, hepatic steatosis, glucose tolerance, and systemic inflammation in HFHS-fed mice. Moreover, WLT supplement altered the composition of gut microbiota, which contributed at least in part, to the anti-NAFLD effect. Meanwhile, WLT improved the intestinal integrity and comprehensively modulated the expression of hepatic genes in HFHS mice, particularly reducing the expression of genes in the toll-like receptor-mediated inflammatory pathway.<br><br>CONCLUSION: WLT is protective against NAFLD formation induced by an HFHS diet, and its effect is associated with the modulation of gut microbiota and inflammation, highlighting the potential of WLT to reduce the risk of metabolic disorders as a functional dietary supplement.}, }
@article {pmid34403381, year = {2021}, author = {Yao, ZW and Yang, X and Zhao, BC and Deng, F and Jiang, YM and Pan, WY and Chen, XD and Zhou, BW and Zhang, WJ and Hu, JJ and Zhu, L and Liu, KX}, title = {Predictive and Preventive Potential of Preoperative Gut Microbiota in Chronic Postoperative Pain in Breast Cancer Survivors.}, journal = {Anesthesia and analgesia}, volume = {}, number = {}, pages = {}, doi = {10.1213/ANE.0000000000005713}, pmid = {34403381}, issn = {1526-7598}, abstract = {BACKGROUND: Evidence suggests a potential relationship between gut microbiota and chronic postoperative pain (CPP). This study aimed to explore the predictive and preventive potential of preoperative gut microbiota in CPP in breast cancer survivors.<br><br>METHODS: In the clinical experiments, we designed a nested case-control study to compared preoperative gut microbiota of breast cancer survivors with and without CPP using 16s rRNA sequencing. The primary outcome was clinically meaningful pain in or around the operative area 3 months after surgery. Logistic prediction models based on previously identified risk factors for CPP in breast cancer survivors were tested with and without differential bacteria to evaluate the model's potential for improvement with the addition of gut microbiota information. In the animal experiments, preoperative fecal microbiota was transplanted from patients with and without CPP to mice, and a spared nerve injury (SNI) model was used to mimic neuropathic pain in CPP. Mechanical hyperalgesia and the expression of markers of spinal microglia and peroxisome proliferator-activated receptor-γ (PPAR-γ) were assessed.<br><br>RESULTS: Sixty-six CPP patients and 66 matched controls were analyzed. Preoperative gut microbiota composition was significantly different in the 2 groups at phylus, family, and genera levels. The discrimination of the clinical prediction model (determined by area under the receiver operating characteristic curve) improved by 0.039 and 0.099 after the involvement of differential gut microbiota at the family and genus levels, respectively. After fecal microbiota transplantation (FMT), "CPP microbiota" recipient mice exhibited significantly increased mechanical hyperalgesia and decreased expression of Ppar-γ and arginase-1 (Arg-1) in the spinal cord.<br><br>CONCLUSIONS: Preoperative gut microbiota has the potential to predict and prevent the development of CPP and plays a causal role in its development via the PPAR-γ-microglia pathway in the spinal cord. Thus, it could be targeted to develop a prevention strategy for CPP in breast cancer survivors.}, }
@article {pmid34402648, year = {2021}, author = {Olekhnovich, EI and Ivanov, AB and Ulyantsev, VI and Ilina, EN}, title = {Separation of Donor and Recipient Microbial Diversity Allows Determination of Taxonomic and Functional Features of Gut Microbiota Restructuring following Fecal Transplantation.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0081121}, doi = {10.1128/mSystems.00811-21}, pmid = {34402648}, issn = {2379-5077}, abstract = {Fecal microbiota transplantation (FMT) is currently used in medicine to treat recurrent clostridial colitis and other intestinal diseases. However, neither the therapeutic mechanism of FMT nor the mechanism that allows the donor bacteria to colonize the intestine of the recipient has yet been clearly described. From a biological point of view, FMT can be considered a useful model for studying the ecology of host-associated microbial communities. FMT experiments can shed light on the relationship features between the host and its gut microbiota. This creates the need for experimentation with approaches to metagenomic data analysis which may be useful for the interpretation of observed biological phenomena. Here, the recipient intestine colonization analysis tool (RECAST) novel computational approach is presented, which is based on the metagenomic read sorting process per their origin in the recipient's post-FMT stool metagenome. Using the RECAST algorithm, taxonomic/functional annotation, and machine learning approaches, the metagenomes from three FMT studies, including healthy volunteers, patients with clostridial colitis, and patients with metabolic syndrome, were analyzed. Using our computational pipeline, the donor-derived and recipient-derived microbes which formed the recipient post-FMT stool metagenomes (successful microbes) were identified. Their presence is well explained by a higher relative abundance in donor/pre-FMT recipient metagenomes or other metagenomes from the human population. In addition, successful microbes are enriched with gene groups potentially related to antibiotic resistance, including antimicrobial peptides. Interestingly, the observed reorganization features are universal and independent of the disease. IMPORTANCE We assumed that the enrichment of successful gut microbes by lantibiotic/antibiotic resistance genes can be related to gut microbiota colonization resistance by third-party microbe phenomena and resistance to bacterium-derived or host-derived antimicrobial substances. According to this assumption, competition between the donor-derived and recipient-derived microbes as well as host immunity may play a key role in the FMT-related colonization and redistribution of recipient gut microbiota structure.}, }
@article {pmid34400407, year = {2021}, author = {Derosa, L and Routy, B and Desilets, A and Daillère, R and Terrisse, S and Kroemer, G and Zitvogel, L}, title = {Microbiota-Centered Interventions: The Next Breakthrough in Immuno-Oncology?.}, journal = {Cancer discovery}, volume = {}, number = {}, pages = {}, doi = {10.1158/2159-8290.CD-21-0236}, pmid = {34400407}, issn = {2159-8290}, abstract = {The cancer-immune dialogue subject to immuno-oncological intervention is profoundly influenced by microenvironmental factors. Indeed, the mucosal microbiota-and more specifically, the intestinal ecosystem-influences the tone of anticancer immune responses and the clinical benefit of immunotherapy. Antibiotics blunt the efficacy of immune checkpoint inhibitors (ICI), and fecal microbial transplantation may restore responsiveness of ICI-resistant melanoma. Here, we review the yin and yang of intestinal bacteria at the crossroads between the intestinal barrier, metabolism, and local or systemic immune responses during anticancer therapies. We discuss diagnostic tools to identify gut dysbiosis and the future prospects of microbiota-based therapeutic interventions. SIGNIFICANCE: Given the recent proof of concept of the potential efficacy of fecal microbial transplantation in patients with melanoma primarily resistant to PD-1 blockade, it is timely to discuss how and why antibiotics compromise the efficacy of cancer immunotherapy, describe the balance between beneficial and harmful microbial species in play during therapies, and introduce the potential for microbiota-centered interventions for the future of immuno-oncology.}, }
@article {pmid34398717, year = {2021}, author = {Saul, S and Fuessel, J and Runde, J}, title = {Pediatric Digestive Health and the Gut Microbiome: Existing Therapies and a Look to the Future.}, journal = {Pediatric annals}, volume = {50}, number = {8}, pages = {e336-e342}, doi = {10.3928/19382359-20210720-01}, pmid = {34398717}, issn = {1938-2359}, abstract = {The human gut is host to trillions of microbes that from birth begin interacting with our immune system. Over time this relationship is thought to shape critical aspects of human function such as metabolism, brain development, immune response, and overall gut health. Recent advances in technology have allowed us to begin understanding this complex relationship and have demonstrated that microbes within the gut ecosystem can be influenced by a variety of factors including mode of delivery, diet, and medication exposure, all of which can impact host health in either positive or detrimental ways. Perturbations of gut homeostasis have been implicated in many forms of digestive disease such as inflammatory bowel disease, irritable bowel syndrome, Helicobacter pylori infection, and even in cases of antibiotic-associated diarrhea. As such, researchers have sought methods to either restore gut homeostasis or prevent dysregulation of the gut community, also known as dysbiosis, through an emerging field known as microbial therapeutics. Examples of existing modalities are reviewed here such as prebiotics, probiotics, fecal microbial transplantation, and dietary therapy. As these therapies become further substantiated through research and increasingly desired by patients and their families, there is a need for providers caring for children to familiarize themselves with the existing data and indications for use. As we look to the future, machine-learning algorithms and more readily available next-generation sequencing of fecal samples may allow us to harness data from a person's gut microbiota to predict response to a particular intervention and tailor therapeutic options with an aim toward precision medicine. [Pediatr Ann. 2021;50(8):e336-e342.].}, }
@article {pmid34397627, year = {2021}, author = {Konopelski, P and Konop, M and Perlejewski, K and Bukowska-Osko, I and Radkowski, M and Onyszkiewicz, M and Jaworska, K and Mogilnicka, I and Samborowska, E and Ufnal, M}, title = {Genetically determined hypertensive phenotype affects gut microbiota composition, but not vice versa.}, journal = {Journal of hypertension}, volume = {39}, number = {9}, pages = {1790-1799}, doi = {10.1097/HJH.0000000000002864}, pmid = {34397627}, issn = {1473-5598}, abstract = {OBJECTIVES: Research suggests reciprocal crosstalk between the host and gut bacteria. This study evaluated the interaction between gut microbiota and arterial blood pressure (BP) in rats.<br><br>METHODS: Continuous telemetry recordings of BP were started in 7-week-old normotensive Wistar--Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Two weeks later, half of the WKY and SHR were subjected to cross-transplantation of fecal matter, with stools harvested from either WKY or SHR and BP measurements until the age of 14 weeks. The composition of gut bacteria was assessed through analysis of the bacterial 16S ribosomal RNA gene sequence. The concentration of microbiota-derived metabolites was evaluated using HPLC-MS.<br><br>RESULTS: There was a significant difference between WKY and SHR in the composition of gut bacteria at the start and end of the study. This was accompanied by significant histological differences in the colon. SHR, but not WKY, showed a gradual increase in BP throughout the experiment. For both WKY and SHR, there was no significant difference in BP or metabolic parameters between animals receiving fecal transplantation from either SHR or WKY.<br><br>CONCLUSION: Genetically induced hypertension in SHR is associated with alterations in the composition of gut bacteria and histological morphology of the colon. An inter-strain fecal transplant does not affect BP and does not produce long-term changes in gut bacteria composition. We propose that the impact of the host genotype and/or phenotype on the gut bacteria may be greater than the impact of the gut bacteria on the host BP.}, }
@article {pmid34395484, year = {2021}, author = {Cui, J and Lin, Z and Tian, H and Yang, B and Zhao, D and Ye, C and Li, N and Qin, H and Chen, Q}, title = {Long-Term Follow-Up Results of Fecal Microbiota Transplantation for Irritable Bowel Syndrome: A Single-Center, Retrospective Study.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {710452}, doi = {10.3389/fmed.2021.710452}, pmid = {34395484}, issn = {2296-858X}, abstract = {Objective: This study aimed to investigate the long-term efficacy of fecal microbiota transplantation (FMT) in patients with irritable bowel syndrome (IBS). Study Methods: In this single-center long-term follow-up study, FMT treatment was administered to patients with moderate to severe IBS (IBS severity scoring system (IBS-SSS) > 175). After 1 year of treatment, it was decided whether to repeat FMT based on IBS-SSS score (IBS-SSS > 175). Baseline characteristics before and after FMT and questionnaires were completed at 1, 3, 6, 12, 24, 36, 48, and 60 months after FMT. The study outcomes included treatment efficacy rates, change of IBS-SSS, IBS-specific quality of life and fatigue, effect on stool frequency, Bristol Stool Scale for IBS-C and IBS-D, and side effects. Results: A total of 227 patients (47.58% IBS-C, 39.21% IBS-D, and 13.22% IBS-M) were recruited (142 females and 85 males with a mean age of 41.89 ± 13.57 years). The efficacy rates were 108 (51.92%), 147 (74.62%), 125 (74.41 %), 88 (71.54%), 78 (75.00%), 65 (73.03%), 45 (61.64%), and 37 (62.71%) at different follow-up time points. The total IBS-SSS score was 321.37 ± 73.89 before FMT, which significantly decreased after 1 month. The IBS-specific quality of life (IBS-QoL) score was 40.24 ± 11.34 before FMT, increased gradually, and was significantly higher at 3 months compared to before FMT. The total Fatigue Assessment Scale (FAS) score was 47 ± 8.64 before FMT and was significantly lower at 3 months. During follow-up, 89 (39.21%) side effects occurred that were alleviated by symptomatic treatment, and no serious adverse events were detected. Conclusion: Based on 60 months of long-term follow-up, the safety and efficacy of FMT for IBS was established. However, as the treatment effect declines over time, periodic and repetitive FMT is required for a sustained effect.}, }
@article {pmid34395308, year = {2021}, author = {Jian, Y and Zhang, D and Liu, M and Wang, Y and Xu, ZX}, title = {The Impact of Gut Microbiota on Radiation-Induced Enteritis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {586392}, doi = {10.3389/fcimb.2021.586392}, pmid = {34395308}, issn = {2235-2988}, abstract = {Radiotherapy is an important treatment for abdominal tumors. A critical side effect for this therapy is enteritis. In this review, we aim to summarize recent findings in radiation enteritis, in particular the role of gut microbiota dysbiosis in the development and therapy of the disease. Gut microbiota dysbiosis plays an important role in the occurrence of various diseases, such as radiation enteritis. Abdominal radiation results in changes in the composition of microbiota and reduces its diversity, which is mainly reflected in the decrease of Lactobacillus spp. and Bifidobacterium spp. and increase of Escherichia coli and Staphylococcus spp. Gut microbiota dysbiosis aggravates radiation enteritis, weakens intestinal epithelial barrier function, and promotes inflammatory factor expression. Pathogenic Escherichia coli induce the rearrangement and redistribution of claudin-1, occludin, and ZO-1 in tight junctions, a critical component in intestinal epithelial barrier. In view of the role that microbiome plays in radiation enteritis, we believe that intestinal flora could be a potential biomarker for the disease. Correction of microbiome by application of probiotics, fecal microbiota transplantation (FMT), and antibiotics could be an effective method for the prevention and treatment of radiation-induced enteritis.}, }
@article {pmid34391441, year = {2021}, author = {Han, SK and Kim, JK and Park, HS and Shin, YJ and Kim, DH}, title = {Chaihu-Shugan-San (Shihosogansan) alleviates restraint stress-generated anxiety and depression in mice by regulating NF-κB-mediated BDNF expression through the modulation of gut microbiota.}, journal = {Chinese medicine}, volume = {16}, number = {1}, pages = {77}, pmid = {34391441}, issn = {1749-8546}, support = {2017R1A5A2014768//National Research Foundation of Korea/ ; }, abstract = {BACKGROUND: Chaihu-Shugan-San (CSS, named Shihosogansan in Korean), a Chinese traditional medicine, is frequently used to treat anxiety and depression. Psychiatric disorders including depression are associated with gut dysbiosis. Therefore, to comprehend gut microbiota-involved anti-depressive effect of CSS, we examined its effect on restraint stress (RS)-induced depression and gut dysbiosis in mice METHODS: CSS was extracted with water in boiling water bath and freeze-dried. Anxiety and depression was induced in C57BL/6 mice by exposure to RS. Anxiety- and depression-like behaviors were measured in the light/dark transition and elevated plus maze tasks, forced swimming test, and tail suspension test. Biomarkers were assayed by using the enzyme-linked immunosorbent assay and immunoblotting. The gut microbiota composition was analyzed by Illumina iSeq sequencer.<br><br>RESULTS: CSS significantly reduced the RS-induced anxiety- and depression-like behaviors in mice. CSS suppressed the RS-induced activation of NF-κB and expression of interleukin (IL)-6 and increased the RS-suppressed expression of brain-derived neurotrophic factor (BDNF). Furthermore, CSS suppressed the RS-induced IL-6 and corticosterone level in the blood and IL-6 expression and myeloperoxidase activity in the colon. CSS decreased the RS-induced γ-Proteobacteria population in gut microbiota, while the RS-suppressed Lactobacillaceae, Prevotellaceae, and AC160630_f populations increased. Fecal transplantation of vehicle-treated control or RS/CSS-treated mice into RS-exposed mice significantly mitigated RS-induced anxity- and depression-like behaviors, suppressed the NF-κB activation in the hippocampus and colon, and reduced the IL-6 and corticosterone levels in the blood. These fecal microbiota transplantations suppressed RS-induced Desulfovibrionaceae and γ-Proteobacteria populations and increased RS-suppressed Lactobacillaceae and Prevotellaceae poulation in the gut microbiota.<br><br>CONCLUSIONS: CSS alleviated anxiety and depression by inducing NF-κB-involved BDNF expression through the regulation of gut inflammation and microbiota.}, }
@article {pmid34203292, year = {2021}, author = {Szczyrek, M and Bitkowska, P and Chunowski, P and Czuchryta, P and Krawczyk, P and Milanowski, J}, title = {Diet, Microbiome, and Cancer Immunotherapy-A Comprehensive Review.}, journal = {Nutrients}, volume = {13}, number = {7}, pages = {}, pmid = {34203292}, issn = {2072-6643}, mesh = {Animals ; Anti-Bacterial Agents ; Antibodies, Monoclonal, Humanized ; Bacteria/immunology ; Diet/*methods ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/*immunology ; Humans ; Immunotherapy/*methods ; Neoplasms/*therapy ; Obesity ; Probiotics/therapeutic use ; Thiamine ; Vitamin D ; }, abstract = {The immune system plays a key role in cancer suppression. Immunotherapy is widely used as a treatment method in patients with various types of cancer. Immune checkpoint blockade using antibodies, such as anti-PD-1, anti-PD-L1, and anti-CTLA-4, is currently gaining popularity. A systematic literature search was executed, and all available data was summarized. This review shows that specific dietary patterns (such as, e.g., animal-based, vegetarian, or Mediterranean diet) alter the gut microbiome's composition. An appropriate intestinal microbiota structure might modulate the function of human immune system, which affects the bodily anti-cancer response. This paper shows also that specific bacteria species inhabiting the gastrointestinal tract can have a beneficial influence on the efficacy of immunotherapy. Antibiotics weaken gut bacteria and worsen the immune checkpoint blockers' efficacy, whereas a faecal microbiota transplant or probiotics supplementation may help restore bacterial balance in the intestine. Other factors (like vitamins, glucose, or BMI) change the cancer treatment response, as well. This review demonstrates that there is a strong association between one's diet, gut microbiome composition, and the outcome of immunotherapy. However, further investigation on this subject is required.}, }
@article {pmid34383708, year = {2021}, author = {Gholam-Mostafaei, FS and Yadegar, A and Asadzadeh Aghdaei, H and Shahrokh, S and Ebrahimi Daryani, N and Zali, MR}, title = {Fecal microbiota transplantation for recurrent Clostridioides difficile infection in patients with concurrent ulcerative colitis.}, journal = {Acta microbiologica et immunologica Hungarica}, volume = {}, number = {}, pages = {}, doi = {10.1556/030.2021.01498}, pmid = {34383708}, issn = {1588-2640}, abstract = {Treatment of recurrent Clostridioides difficile infection (rCDI) has emerged as an important management dilemma particularly in patients with underlying inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) has been used as a safe and highly effective treatment option for rCDI refractory to standard antibiotic therapies. The aim of this study was to report the efficacy of FMT in Iranian rCDI patients with concurrent IBD. A total of seven consecutive patients with ulcerative colitis (UC) who had experienced 3 episodes of rCDI were enrolled in this study. All patients received at least a single FMT administered during colonoscopy by direct infusion of minimally processed donor stool. Patients were followed for a minimum of 6 months for assessment of treatment efficacy and adverse events (AEs) attributable to FMT. All 7 UC patients (100%) experienced a durable clinical response to a single FMT following 2 months after the procedure. One patient received a second FMT in which a successful resolution of rCDI was ultimately achieved. No serious AEs from FMT were noted. FMT through colonoscopy was a safe, simple and effective alternative treatment approach for rCDI in patients with underlying IBD. However, its use and efficacy should be pursued in long-term prospective controlled trials.}, }
@article {pmid34382390, year = {2021}, author = {Zhao, Y and Liu, S and Tang, Y and You, T and Xu, H}, title = {Lactobacillus rhamnosus GG Ameliorated Long-Term Exposure to TiO2 Nanoparticles Induced Microbiota-Mediated Liver and Colon Inflammation and Fructose-Caused Metabolic Abnormality in Metabolism Syndrome Mice.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.1c03301}, pmid = {34382390}, issn = {1520-5118}, abstract = {A huge number of titanium dioxide nanoparticles (TiO2 NPs) exist in confectionery foods, which is a high-risk factor for development of diet-induced metabolism syndrome (MetS). In this study, we built a high fructose drinking-induced MetS mouse model, and oral intake of 20 mg/kg TiO2 NPs was administered for 8 weeks. Significant pathological changes and inflammatory factors of overproduction were detected in the liver and colon. The 16S rDNA sequencing analysis results indicated that TiO2 NPs evidently and further perturbed the gut microbiota diversity, compositions, and KEGG pathways in MetS mice. Fecal microbiota transplant experiment proved that TiO2 NPs-altered gut microbiota drives liver and colon inflammation damage. More importantly, oral supplementation of Lactobacillus rhamnosus GG (LGG) ameliorated not only the TiO2 NPs-induced inflammation but also the fructose-caused metabolic abnormality. LGG recovered the gut dysbiosis and decreased the abundance of inflammation-related bacteria (Desulfovibrionaceae, Clostridia, and Proteobacteria), thereby protecting against TiO2 NPs-induced severe inflammation damage. Our study suggests the necessity of assessing the toxic effects of foodborne nanoparticles on the chronic disease population and potential usefulness of probiotics as prophylactic and therapeutic.}, }
@article {pmid34381040, year = {2021}, author = {Wang, H and Yang, F and Zhang, S and Xin, R and Sun, Y}, title = {Genetic and environmental factors in Alzheimer's and Parkinson's diseases and promising therapeutic intervention via fecal microbiota transplantation.}, journal = {NPJ Parkinson's disease}, volume = {7}, number = {1}, pages = {70}, pmid = {34381040}, issn = {2373-8057}, abstract = {Neurodegenerative diseases are characterized by neuronal impairment and loss of function, and with the major shared histopathological hallmarks of misfolding and aggregation of specific proteins inside or outside cells. Some genetic and environmental factors contribute to the promotion of the development and progression of neurodegenerative diseases. Currently, there are no effective treatments for neurodegenerative diseases. It has been revealed that bidirectional communication exists between the brain and the gut. The gut microbiota is a changeable and experience-dependent ecosystem and can be modified by genetic and environmental factors. The gut microbiota provides potential therapeutic targets that can be regulated as new interventions for neurodegenerative diseases. In this review, we discuss genetic and environmental risk factors for neurodegenerative diseases, summarize the communication among the components of the microbiota-gut-brain axis, and discuss the treatment strategy of fecal microbiota transplantation (FMT). FMT is a promising treatment for neurodegenerative diseases, and restoration of the gut microbiota to a premorbid state is a novel goal for prevention and treatment strategies.}, }
@article {pmid34378656, year = {2021}, author = {Liaqat, I and Ali, NM and Arshad, N and Sajjad, S and Rashid, F and Hanif, U and Ara, C and Ulfat, M and Andleeb, S and Awan, UF and Bibi, A and Mubin, M and Ali, S and Tahir, HM and Ul-Haq, I}, title = {Gut dysbiosis, inflammation and type 2 diabetes in mice using synthetic gut microbiota from diabetic humans.}, journal = {Brazilian journal of biology = Revista brasleira de biologia}, volume = {83}, number = {}, pages = {e242818}, doi = {10.1590/1519-6984.242818}, pmid = {34378656}, issn = {1678-4375}, mesh = {Animals ; Bacteroides ; Bacteroidetes ; *Diabetes Mellitus, Type 2 ; Diet, High-Fat/adverse effects ; Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; Inflammation ; Mice ; Mice, Inbred C57BL ; Prevotella ; RNA, Ribosomal, 16S/genetics ; Ruminococcus ; }, abstract = {The study was aimed to assess impact of high fat diet (HFD) and synthetic human gut microbiota (GM) combined with HFD and chow diet (CD) in inducing type-2 diabetes (T2D) using mice model. To our knowledge, this is the first study using selected human GM transplantation via culture based method coupled dietary modulation in mice for in vivo establishment of inflammation leading to T2D and gut dysbiosis. Twenty bacteria (T2D1-T2D20) from stool samples of confirmed T2D subjects were found to be morphologically different and subjected to purification on different media both aerobically and anerobically, which revealed seven bacteria more common among 20 isolates on the basis of biochemical characterization. On the basis of 16S rRNA gene sequencing, these seven isolates were identified as Bacteroides stercoris (MT152636), Lactobacillus acidophilus (MT152637), Lactobacillus salivarius (MT152638), Ruminococcus bromii (MT152639), Klebsiella aerogenes (MT152640), Bacteroides fragilis (MT152909), Clostridium botulinum (MT152910). The seven isolates were subsequently used as synthetic gut microbiome (GM) for their role in inducing T2D in mice. Inbred strains of albino mice were divided into four groups and were fed with CD, HFD, GM+HFD and GM+CD. Mice receiving HFD and GM+modified diet (CD/HFD) showed highly significant (P<0.05) increase in weight and blood glucose concentration as well as elevated level of inflammatory cytokines (TNF-α, IL-6, and MCP-1) compared to mice receiving CD only. The 16S rRNA gene sequencing of 11 fecal bacteria obtained from three randomly selected animals from each group revealed gut dysbiosis in animals receiving GM. Bacterial strains including Bacteroides gallinarum (MT152630), Ruminococcus bromii (MT152631), Lactobacillus acidophilus (MT152632), Parabacteroides gordonii (MT152633), Prevotella copri (MT152634) and Lactobacillus gasseri (MT152635) were isolated from mice treated with GM+modified diet (HFD/CD) compared to strains Akkermansia muciniphila (MT152625), Bacteriodes sp. (MT152626), Bacteroides faecis (MT152627), Bacteroides vulgatus (MT152628), Lactobacillus plantarum (MT152629) which were isolated from mice receiving CD/HFD. In conclusion, these findings suggest that constitution of GM and diet plays significant role in inflammation leading to onset or/and possibly progression of T2D. .}, }
@article {pmid34376591, year = {2021}, author = {Kurokawa, S}, title = {[The Link Between Gut Microbiota and Cerebral Functions: An Update on the Pathogenesis and Treatment of Functional Gastrointestinal Disorders].}, journal = {Brain and nerve = Shinkei kenkyu no shinpo}, volume = {73}, number = {8}, pages = {857-862}, doi = {10.11477/mf.1416201852}, pmid = {34376591}, issn = {1881-6096}, mesh = {Dysbiosis/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Diseases/therapy ; *Gastrointestinal Microbiome ; Humans ; *Probiotics/therapeutic use ; }, abstract = {Recent studies have focused on the mechanism of brain effects on functional gastrointestinal disorders, through dysbiosis of the gut microbiota. Herein, we summarize the known pathogeneses of various functional gastrointestinal disorders relative to the gut microbiota, and discuss future gut microbiota-focused interventions for restoring dysbiosis, including probiotics and fecal microbiota transplantation.}, }
@article {pmid34368762, year = {2021}, author = {Puca, P and Petito, V and Laterza, L and Lopetuso, LR and Neri, M and Del Chierico, F and Boskoski, I and Gasbarrini, A and Scaldaferri, F}, title = {Bariatric procedures and microbiota: patient selection and outcome prediction.}, journal = {Therapeutic advances in gastrointestinal endoscopy}, volume = {14}, number = {}, pages = {26317745211014746}, pmid = {34368762}, issn = {2631-7745}, abstract = {Obesity is a major health issue throughout the world and bariatric surgery plays a key role in its management and treatment. The role of microbiota in determining the pathogenesis of obesity has been widely studied, while its role in determining the outcome of bariatric surgery is an emerging issue that will be an outcome in near future studies. Studies on mice first showed the key role of microbiota in determining obesity, highlighting the fat mass increase in mice transplanted with microbiota from fat individuals, as well as the different microbiota composition between mice undergone to low-fat or high-fat diets. This led to characterize the asset of microbiota composition in obesity: increased abundance of Firmicutes, reduced abundance of Bacteroidetes and other taxonomical features. Variations on the composition of gut microbiome have been detected in patients undergone to diet and/or bariatric surgery procedures. Patients undergone to restricting diets showed lower level of trimethylamine N-oxide and other metabolites strictly associated to microbiome, as well as patients treated with bariatric surgery showed, after the procedure, changes in the relative abundance of Bacteroidetes, Firmicutes and other phyla with a role in the pathogenesis of obesity. Eventually, studies have been led about the effects that the modification of microbiota could have on obesity itself, mainly focusing on elements like fecal microbiota transplantation and probiotics such as inulin. This series of studies and considerations represent the first step in order to select patients eligible to bariatric surgery and to predict their outcome.}, }
@article {pmid34367617, year = {2021}, author = {Manzoor, SE and Zaman, S and Whalley, C and Inglis, D and Bosworth, A and Kidd, M and Shabir, S and Quraishi, N and Green, CA and Iqbal, T and Beggs, AD}, title = {Multi-modality detection of SARS-CoV-2 in faecal donor samples for transplantation and in asymptomatic emergency surgical admissions.}, journal = {F1000Research}, volume = {10}, number = {}, pages = {373}, pmid = {34367617}, issn = {2046-1402}, mesh = {*COVID-19 ; Fecal Microbiota Transplantation ; Humans ; RNA, Viral/genetics ; Real-Time Polymerase Chain Reaction ; *SARS-CoV-2 ; }, abstract = {Background: Faecal transplantation is an evidence-based treatment for Clostridioides difficile. Patients infected with SARS-CoV-2 have been shown to shed the virus in stool for up to 33 days, well beyond the average clearance time for upper respiratory tract shedding. We carried out an analytical and clinical validation of reverse-transcriptase quantitative (RT-qPCR) as well as LAMP, LamPORE and droplet digital PCR in the detection of SARS-CoV-2 RNA in stool from donated samples for faecal microbiota transplantation (FMT), spiked samples and asymptomatic inpatients in an acute surgical unit. Methods: Killed SARS-CoV-2 viral lysate and extracted RNA was spiked into donor stool &amp; FMT and a linear dilution series from 10 -1 to 10 -5 and tested via RT-qPCR, LAMP, LamPORE and ddPCR against SARS-CoV-2. Patients admitted to the critical care unit with symptomatic SARS-CoV-2 and sequential asymptomatic patients from acute presentation to an acute surgical unit were also tested. Results: In a linear dilution series, detection of the lowest dilution series was found to be 8 copies per microlitre of sample. Spiked lysate samples down to 10 -2 dilution were detected in FMT samples using RTQPCR, LamPORE and ddPCR and down to 10 -1 with LAMP. In symptomatic patients 5/12 had detectable SARS-CoV-2 in stool via RT-qPCR and 6/12 via LamPORE, and in 1/97 asymptomatic patients via RT-qPCR. Conclusion: RT-qPCR can be detected in FMT donor samples using RT-qPCR, LamPORE and ddPCR to low levels using validated pathways. As previously demonstrated, nearly half of symptomatic and less than one percent of asymptomatic patients had detectable SARS-CoV-2 in stool.}, }
@article {pmid34367139, year = {2021}, author = {Qu, Y and Li, X and Xu, F and Zhao, S and Wu, X and Wang, Y and Xie, J}, title = {Kaempferol Alleviates Murine Experimental Colitis by Restoring Gut Microbiota and Inhibiting the LPS-TLR4-NF-κB Axis.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {679897}, pmid = {34367139}, issn = {1664-3224}, abstract = {Intestinal microbiota dysbiosis is an established characteristic of ulcerative colitis (UC). Regulating the gut microbiota is an attractive alternative UC treatment strategy, considering the potential adverse effects of synthetic drugs used to treat UC. Kaempferol (Kae) is an anti-inflammatory and antioxidant flavonoid derived from a variety of medicinal plants. In this study, we determined the efficacy and mechanism of action of Kae as an anti-UC agent in dextran sulfate sodium (DSS)-induced colitis mice. DSS challenge in a mouse model of UC led to weight loss, diarrhea accompanied by mucous and blood, histological abnormalities, and shortening of the colon, all of which were significantly alleviated by pretreatment with Kae. In addition, intestinal permeability was shown to improve using fluorescein isothiocyanate (FITC)-dextran administration. DSS-induced destruction of the intestinal barrier was also significantly prevented by Kae administration via increases in the levels of ZO-1, occludin, and claudin-1. Furthermore, Kae pretreatment decreased the levels of IL-1β, IL-6, and TNF-α and downregulated transcription of an array of inflammatory signaling molecules, while it increased IL-10 mRNA expression. Notably, Kae reshaped the intestinal microbiome by elevating the Firmicutes to Bacteroidetes ratio; increasing the linear discriminant analysis scores of beneficial bacteria, such as Prevotellaceae and Ruminococcaceae; and reducing the richness of Proteobacteria in DSS-challenged mice. There was also an evident shift in the profile of fecal metabolites in the Kae treatment group. Serum LPS levels and downstream TLR4-NF-κB signaling were downregulated by Kae supplementation. Moreover, fecal microbiota transplantation from Kae-treated mice to the DSS-induced mice confirmed the effects of Kae on modulating the gut microbiota to alleviate UC. Therefore, Kae may exert protective effects against colitis mice through regulating the gut microbiota and TLR4-related signaling pathways. This study demonstrates the anti-UC effects of Kae and its potential therapeutic mechanisms, and offers novel insights into the prevention of inflammatory diseases using natural products.}, }
@article {pmid34364884, year = {2021}, author = {McCarthy, S and Barrett, M and Kirthi, S and Pellanda, P and Vlckova, K and Tobin, AM and Murphy, M and Shanahan, F and O'Toole, PW}, title = {Altered Skin and Gut Microbiome in Hidradenitis Suppurativa.}, journal = {The Journal of investigative dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jid.2021.05.036}, pmid = {34364884}, issn = {1523-1747}, abstract = {Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by the formation of nodules, abscesses, and fistula at intertriginous sites. The skin-gut axis is an area of emerging research in inflammatory skin disease and is a potential contributory factor to the pathogenesis of HS. 59 patients with HS provided fecal samples, nasal and skin swabs of affected sites for analysis. 30 healthy controls provided fecal samples and 20 healthy controls provided nasal and skin swabs. We performed bacterial 16S rRNA gene amplicon sequencing on total DNA derived from the samples. Microbiome alpha diversity was significantly lower in the fecal, skin and nasal samples of individuals with HS which may be secondary to disease biology or related to antibiotic usage. Ruminococcus gnavus was more abundant in the fecal microbiome of individuals with HS, which is also reported in Crohn's disease (CD), suggesting comorbidity due to shared gut microbiota alterations. Finegoldia magna was over-abundant in HS skin samples relative to healthy controls. It is possible local inflammation is driven by F. magna through promoting the formation of neutrophil extracellular traps (NET). These alterations in both the gut and skin microbiome in HS warrant further exploration, and therapeutic strategies including fecal microbiota transplant (FMT) or bacteriotherapy could be of benefit.}, }
@article {pmid34362925, year = {2021}, author = {Zhang, AN and Gaston, JM and Dai, CL and Zhao, S and Poyet, M and Groussin, M and Yin, X and Li, LG and van Loosdrecht, MCM and Topp, E and Gillings, MR and Hanage, WP and Tiedje, JM and Moniz, K and Alm, EJ and Zhang, T}, title = {An omics-based framework for assessing the health risk of antimicrobial resistance genes.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {4765}, pmid = {34362925}, issn = {2041-1723}, abstract = {Antibiotic resistance genes (ARGs) are widespread among bacteria. However, not all ARGs pose serious threats to public health, highlighting the importance of identifying those that are high-risk. Here, we developed an 'omics-based' framework to evaluate ARG risk considering human-associated-enrichment, gene mobility, and host pathogenicity. Our framework classifies human-associated, mobile ARGs (3.6% of all ARGs) as the highest risk, which we further differentiate as 'current threats' (Rank I; 3%) - already present among pathogens - and 'future threats' (Rank II; 0.6%) - novel resistance emerging from non-pathogens. Our framework identified 73 'current threat' ARG families. Of these, 35 were among the 37 high-risk ARGs proposed by the World Health Organization and other literature; the remaining 38 were significantly enriched in hospital plasmids. By evaluating all pathogen genomes released since framework construction, we confirmed that ARGs that recently transferred into pathogens were significantly enriched in Rank II ('future threats'). Lastly, we applied the framework to gut microbiome genomes from fecal microbiota transplantation donors. We found that although ARGs were widespread (73% of genomes), only 8.9% of genomes contained high-risk ARGs. Our framework provides an easy-to-implement approach to identify current and future antimicrobial resistance threats, with potential clinical applications including reducing risk of microbiome-based interventions.}, }
@article {pmid34359501, year = {2021}, author = {Lee, BH and Hsu, WH and Chien, HY and Hou, CY and Hsu, YT and Chen, YZ and Wu, SC}, title = {Applications of Lactobacillus acidophilus-Fermented Mango Protected Clostridioides difficile Infection and Developed as an Innovative Probiotic Jam.}, journal = {Foods (Basel, Switzerland)}, volume = {10}, number = {7}, pages = {}, pmid = {34359501}, issn = {2304-8158}, abstract = {Clostridioides difficile infection (CDI) is a large intestine disease caused by toxins produced by the spore-forming bacterium C. difficile, which belongs to Gram-positive bacillus. Using antibiotics treatment disturbances in the gut microbiota and toxins produced by C. difficile disrupt the intestinal barrier. Some evidence indicates fecal microbiota transplantation and probiotics may decrease the risk of CDI recurrence. This study aimed to evaluate the efficacy of fermented mango by using the lactic acid bacteria Lactobacillus acidophilus and develop innovative products in the form of fermented mango jam. L. acidophilus-fermented mango products inhibited the growth of C. difficile while promoting the growth of next-generation probiotic Faecalibacterium prausnitzii. Both supernatant and precipitate of mango-fermented products prevented cell death in gut enterocyte-like Caco-2 cells against C. difficile infection. Mango-fermented products also protected gut barrier function by elevating the expression of tight junction proteins. Moreover, L. acidophilus-fermented mango jam with high hydrostatic pressure treatment had favorable textural characteristics and sensory quality.}, }
@article {pmid34356911, year = {2021}, author = {Gozalbo-Rovira, R and Santiso-Bellón, C and Buesa, J and Rubio-Del-Campo, A and Vila-Vicent, S and Muñoz, C and Yebra, MJ and Monedero, V and Rodríguez-Díaz, J}, title = {Microbiota Depletion Promotes Human Rotavirus Replication in an Adult Mouse Model.}, journal = {Biomedicines}, volume = {9}, number = {7}, pages = {}, pmid = {34356911}, issn = {2227-9059}, support = {AGL2017-84165-C2-1-R//Ministerio de Ciencia y Tecnología/ ; AGL2017-84165-C2-2-R//Ministerio de Ciencia y Tecnología/ ; }, abstract = {Intestinal microbiota-virus-host interaction has emerged as a key factor in mediating enteric virus pathogenicity. With the aim of analyzing whether human gut bacteria improve the inefficient replication of human rotavirus in mice, we performed fecal microbiota transplant (FMT) with healthy infants as donors in antibiotic-treated mice. We showed that a simple antibiotic treatment, irrespective of FMT, resulted in viral shedding for 6 days after challenge with the human rotavirus G1P[8] genotype Wa strain (RVwa). Rotavirus titers in feces were also significantly higher in antibiotic-treated animals with or without FMT but they were decreased in animals subject to self-FMT, where a partial re-establishment of specific bacterial taxons was evidenced. Microbial composition analysis revealed profound changes in the intestinal microbiota of antibiotic-treated animals, whereas some bacterial groups, including members of Lactobacillus, Bilophila, Mucispirillum, and Oscillospira, recovered after self-FMT. In antibiotic-treated and FMT animals where the virus replicated more efficiently, differences were observed in gene expression of immune mediators, such as IL1β and CXCL15, as well as in the fucosyltransferase FUT2, responsible for H-type antigen synthesis in the small intestine. Collectively, our results suggest that antibiotic-induced microbiota depletion eradicates the microbial taxa that restrict human rotavirus infectivity in mice.}, }
@article {pmid34355542, year = {2021}, author = {Lee, MH}, title = {Harness the functions of gut microbiome in tumorigenesis for cancer treatment.}, journal = {Cancer communications (London, England)}, volume = {}, number = {}, pages = {}, doi = {10.1002/cac2.12200}, pmid = {34355542}, issn = {2523-3548}, support = {2020YFA0803300//National key research and development program/ ; 2018YFC0910300//National key research and development program/ ; 81630072//National Natural Science Foundation of China/ ; KQTD20170810160226082//Shenzhen Municipal Government of China/ ; 2018YFC0910300//China Association for Science and Technology/ ; 2020YFA0803300//China Association for Science and Technology/ ; }, abstract = {It has been shown that gut microbiota dysbiosis leads to physiological changes and links to a number of diseases, including cancers. Thus, many cancer categories and treatment regimens should be investigated in the context of the microbiome. Owing to the availability of metagenome sequencing and multiomics studies, analyses of species characterization, host genetic changes, and metabolic profile of gut microbiota have become feasible, which has facilitated an exponential knowledge gain about microbiota composition, taxonomic alterations, and host interactions during tumorigenesis. However, the complexity of the gut microbiota, with a plethora of uncharacterized host-microbe, microbe-microbe, and environmental interactions, still contributes to the challenge of advancing our knowledge of the microbiota-cancer interactions. These interactions manifest in signaling relay, metabolism, immunity, tumor development, genetic instability, sensitivity to cancer chemotherapy and immunotherapy. This review summarizes current studies/molecular mechanisms regarding the association between the gut microbiota and the development of cancers, which provides insights into the therapeutic strategies that could be harnessed for cancer diagnosis, treatment, or prevention.}, }
@article {pmid34354704, year = {2021}, author = {Wang, D and Shao, S and Zhang, Y and Zhao, D and Wang, M}, title = {Insight Into Polysaccharides From Panax ginseng C. A. Meyer in Improving Intestinal Inflammation: Modulating Intestinal Microbiota and Autophagy.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {683911}, pmid = {34354704}, issn = {1664-3224}, abstract = {Polysaccharides from Panax ginseng C. A. Meyer (P. ginseng) are the main active component of P. ginseng and exhibit significant intestinal anti-inflammatory activity. However, the therapeutic mechanism of the ginseng polysaccharide is unclear, and this hinders the application for medicine or functional food. In this study, a polysaccharide was isolated from P. ginseng (GP). The primary structure and morphology of the GP were studied by HPLC, FT-IR spectroscopy, and scanning electron microscopy (SEM). Further, its intestinal anti-inflammatory activity and its mechanism of function were evaluated in experimental systems using DSS-induced rats, fecal microbiota transplantation (FMT), and LPS-stimulated HT-29 cells. Results showed that GP modulated the structure of gut microbiota and restored mTOR-dependent autophagic dysfunction. Consequently, active autophagy suppressed inflammation through the inhibition of NF-κB, oxidative stress, and the release of cytokines. Therefore, our research provides a rationale for future investigations into the relationship between microbiota and autophagy and revealed the therapeutic potential of GP for inflammatory bowel disease.}, }
@article {pmid34349661, year = {2021}, author = {Choi, YJ and Kim, JE and Lee, SJ and Gong, JE and Son, HJ and Hong, JT and Hwang, DY}, title = {Dysbiosis of Fecal Microbiota From Complement 3 Knockout Mice With Constipation Phenotypes Contributes to Development of Defecation Delay.}, journal = {Frontiers in physiology}, volume = {12}, number = {}, pages = {650789}, pmid = {34349661}, issn = {1664-042X}, abstract = {Significant phenotypes for constipation were detected in complement 3 (C3) knockout (KO) mice, although no research has been conducted on an association with alteration of gut microbiota. To investigate the effects of dysbiosis on fecal microbiota from C3 KO mice with constipation, the composition of fecal microbiota was characterized in mid-colons of 16-week-old C3 KO mice, and their function for defecation delay development was examined after fecal microbiota transplantation (FMT) of C3 KO mice. Some significant alterations in constipation phenotypes, including stool parameters and histopathological structure, were detected in 16-week-old C3 KO mice compared to those of wild-type (WT) mice. Fecal microbiota of C3 KO mice exhibited decreases in Anaerocolumna, Caecibacterium, Christensenella, Kineothrix, and Oscillibacter populations and increases in Prevotellamassilia, Reuthenibacterium, Prevotella, Eubacterium, Culturomica, Bacteroides, and Muribaculum populations. In FMT study, key stool parameters, including weight and water content, were remarkably declined in a transplanted KO (KFMT) group of antibiotics-induced depletion of microbiota (AiDM)-WT and AiDM-KO mice, and a similar change was observed in fecal morphology. However, intestine length decreased in only the KFMT group of AiDM-WT mice compared with that of AiDM-KO mice. The mucosal layer and muscle thickness were commonly decreased in the KFMT group of AiDM-WT and AiDM-KO mice, and significant alterations in the crypt structure of Lieberkuhn and molecular regulators, including AQP8, C-kit, and 5-HT, were observed in the same group. Taken together, results of the present study indicate that dysbiosis of fecal microbiota from C3 KO mice with constipation phenotypes has a key role in the induction and regulation of defecation delay.}, }
@article {pmid34347266, year = {2021}, author = {Zhong, Z and Chen, W and Gao, H and Che, N and Xu, M and Yang, L and Zhang, Y and Ye, M}, title = {Fecal Microbiota Transplantation Exerts a Protective Role in MPTP-Induced Parkinson's Disease via the TLR4/PI3K/AKT/NF-κB Pathway Stimulated by α-Synuclein.}, journal = {Neurochemical research}, volume = {}, number = {}, pages = {}, pmid = {34347266}, issn = {1573-6903}, abstract = {Gut microbiota is closely related to the Parkinson's disease (PD) pathogenesis. Additionally, aggregation of α-synuclein (α-syn) is central to PD pathogenesis. Here we identified the further mechanisms of gut microbiota in PD. A mouse model with PD was established via injection of MPTP. Normal or MPTP-induced PD like animals were treated with FMT from healthy normal mice. Pole test and traction test were performed to examine the effects of FMT on motor function of PD mice. Fecal SCFAs were assessed by gas chromatography-mass spectrometry. The α-syn level in the substantia nigra pars compacta (SN) of mice was measured using western blot. Dopaminergic neurons and microglial activation in the SN were analyzed by immunohistochemistry (IHC) and immunofluorescence (IF) staining. FMT alleviated physical impairment, decreased fecal SCFAs in a mouse model of PD. Additionally, FMT decreased the expression of α-syn, as well as inhibited the activation of microglia in the SN, and blocked the TLR4/PI3K/AKT/NF-κB signaling in the SN and striatum. FMT could protect mice against PD via suppressing α-syn expression and inactivating the TLR4/PI3K/AKT/NF-κB signaling.}, }
@article {pmid34346283, year = {2021}, author = {Bajaj, JS and Shamsaddini, A and Fagan, A and McGeorge, S and Gavis, E and Sikaroodi, M and Brenner, LA and Wade, JB and Gillevet, PM}, title = {Distinct gut microbial compositional and functional changes associated with impaired inhibitory control in patients with cirrhosis.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1953247}, pmid = {34346283}, issn = {1949-0984}, support = {I01 CX001076/CX/CSRD VA/United States ; R01 HS025412/HS/AHRQ HHS/United States ; R21 TR002024/TR/NCATS NIH HHS/United States ; R21 TR003095/TR/NCATS NIH HHS/United States ; }, abstract = {Most cirrhosis etiologies, such as alcohol, hepatitis C, and obesity, involve behavior that require the loss of inhibitory control. Once cirrhosis develops, patients can also develop cognitive impairment due to minimal hepatic encephalopathy (MHE). Both processes could have distinct imprints on the gut-liver-brain axis. Determine the impact of inhibitory control versus traditional cirrhosis-related cognitive performance on gut microbial composition and function. Outpatients with cirrhosis underwent two tests for MHE: inhibitory control test (MHEICT, computerized associated with response inhibition) and psychometric hepatic encephalopathy score (MHEPHES, paper-pencil HE-specific associated with subcortical impairment) along with stool collection for metagenomics. MHEICT/not, MHEPHES/not, and discordant (positive on one test but negative on the other) were analyzed for demographics, bacterial species, and gut-brain modules (GBM) using multi-variable analyses. Ninety-seven patients [47 (49%) MHEPHES, 76 (78%) MHEICT, 41 discordant] were enrolled. MHEPHES/not: Cirrhosis severity was worse in MHEPHES without differences in alpha/beta diversity on bacterial species or GBMs. Pathobionts (Enterobacteriaceae) and γ-amino-butryic acid (GABA) synthesis GBM were higher in MHEPHES. MHEICT/not: We found similar cirrhosis severity and metagenomic alpha/beta diversity in MHEICT versus not. However, alpha/beta diversity of GBMs were different in MHEICT versus No-MHE patients. Alistipes ihumii, Prevotella copri, and Eubacterium spp. were higher, while Enterococcus spp. were uniquely lower in MHEICT versus no-MHE and discordant comparisons. GBMs belonging to tryptophan, menaquinone, GABA, glutamate, and short-chain fatty acid synthesis were also unique to MHEICT. Gut microbial signature of impaired inhibitory control, which is associated with addictive disorders that can lead to cirrhosis, is distinct from cirrhosis-related cognitive impairment.}, }
@article {pmid34343321, year = {2021}, author = {Conrad, MA and Kelsen, JR}, title = {Clostridioides difficile Infection in Pediatric Inflammatory Bowel Disease: A Clinician's Dilemma.}, journal = {Journal of the Pediatric Infectious Diseases Society}, volume = {}, number = {}, pages = {}, doi = {10.1093/jpids/piab069}, pmid = {34343321}, issn = {2048-7207}, support = {K23 DK119585/DK/NIDDK NIH HHS/United States ; }, abstract = {Clostridioides difficile infection (CDI) in children with inflammatory bowel disease (IBD) can present and manifest differently from the general population with CDI, and it can worsen the underlying disease course. Furthermore, current clinical assays used to test for CDI do not accurately distinguish between true CDI or colonization. This uncertainty leads to difficulty in identifying the etiology and therapy for symptomatic patients with IBD. Improved diagnostic tests, biomarkers, and safe and effective treatment options are greatly needed for this vulnerable population.}, }
@article {pmid34341834, year = {2021}, author = {Zhang, M and Hong, Y and Wu, W and Li, N and Liu, B and Sun, J and Cao, X and Ye, T and Zhou, L and Liu, C and Yang, C and Zhang, X}, title = {Pivotal role of the gut microbiota in congenital insensitivity to pain with anhidrosis.}, journal = {Psychopharmacology}, volume = {}, number = {}, pages = {}, pmid = {34341834}, issn = {1432-2072}, support = {81974171//Natural Science Foundation Project of China/ ; }, abstract = {BACKGROUND: Increasing evidence has shown that the occurrence and development of various human diseases are closely related to the gut microbiota. We compared the gut microbial communities of human subjects with congenital insensitivity to pain with anhidrosis (CIPA) and healthy controls (HCs) to assess whether fecal microbiota transplantation (FMT) into germ-free mice and mice in acute pain influenced the behaviors of the host.<br><br>METHODS: We utilized 16 s rRNA analysis to compare the gut microbial communities of CIPA subjects and HCs and assessed whether FMT into germ-free mice and mice in acute pain influenced the behaviors of the host.<br><br>RESULTS: In a 16 s RNA analysis, the CIPA group had significant decreases in the relative abundance of 11 bacteria, whereas 7 bacteria were significantly increased. In further animal experiments, the transplantation of fecal samples from CIPA patients to healthy mice significantly increased their scores on both the mechanical withdrawal test and the tail flick test; in an acute plantar incision model, scores were also significantly increased on the mechanical withdrawal test at 4 and 5 days after the operation. Moreover, pseudo-germ-free mice receiving fecal bacteria from patients with CIPA took significantly longer to escape and had a significantly longer path length on training days 1, 2, and 5 and also had fewer platform crossings and spent less time in the target quadrant in the probe trial.<br><br>CONCLUSIONS: Our results suggest that the gut microbiota in CIPA subjects plays a key role in behaviors. Therapeutic strategies for improving the gut microbiota might alleviate CIPA symptoms.}, }
@article {pmid34335628, year = {2021}, author = {Brosseau, C and Selle, A and Duval, A and Misme-Aucouturier, B and Chesneau, M and Brouard, S and Cherbuy, C and Cariou, V and Bouchaud, G and Mincham, KT and Strickland, DH and Barbarot, S and Bodinier, M}, title = {Prebiotic Supplementation During Pregnancy Modifies the Gut Microbiota and Increases Metabolites in Amniotic Fluid, Driving a Tolerogenic Environment In Utero.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {712614}, pmid = {34335628}, issn = {1664-3224}, abstract = {The gut microbiota is influenced by environmental factors such as food. Maternal diet during pregnancy modifies the gut microbiota composition and function, leading to the production of specific compounds that are transferred to the fetus and enhance the ontogeny and maturation of the immune system. Prebiotics are fermented by gut bacteria, leading to the release of short-chain fatty acids that can specifically interact with the immune system, inducing a switch toward tolerogenic populations and therefore conferring health benefits. In this study, pregnant BALB/cJRj mice were fed either a control diet or a diet enriched in prebiotics (Galacto-oligosaccharides/Inulin). We hypothesized that galacto-oligosaccharides/inulin supplementation during gestation could modify the maternal microbiota, favoring healthy immune imprinting in the fetus. Galacto-oligosaccharides/inulin supplementation during gestation increases the abundance of Bacteroidetes and decreases that of Firmicutes in the gut microbiota, leading to increased production of fecal acetate, which was found for the first time in amniotic fluid. Prebiotic supplementation increased the abundance of regulatory B and T cells in gestational tissues and in the fetus. Interestingly, these regulatory cells remained later in life. In conclusion, prebiotic supplementation during pregnancy leads to the transmission of specific microbial and immune factors from mother to child, allowing the establishment of tolerogenic immune imprinting in the fetus that may be beneficial for infant health outcomes.}, }
@article {pmid34335508, year = {2021}, author = {Zhu, F and Ke, Y and Luo, Y and Wu, J and Wu, P and Ma, F and Liu, Y}, title = {Effects of Different Treatment of Fecal Microbiota Transplantation Techniques on Treatment of Ulcerative Colitis in Rats.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {683234}, pmid = {34335508}, issn = {1664-302X}, abstract = {Background: Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease with abdominal pain, mucus, pus and blood in the stool as the main clinical manifestations. The pathogenesis of UC is still not completely clear, and multiple factors, such as genetic susceptibility, immune response, intestinal microecological changes and environmental factors, together lead to the onset of UC. In recent years, the role of intestinal microbiota disturbances on the pathogenesis of UC has received widespread attention. Therefore, fecal microbiota transplantation (FMT), which changes the intestinal microecological environment of UC patients by transplantation of normal fecal bacteria, has attracted increasing attention from researchers. However, there are no guidelines to recommend fresh FMT or frozen FMT in the treatment of UC, and there are few studies on this. Therefore, the purpose of this study was to explore the effects of fresh and frozen FMT methods on the treatment of experimental UC models in rats. Results: Compared with the model control group, all FMT groups achieved better efficacy, mainly manifested as weight gain by the rats, improvements in fecal characteristics and blood stools, reduced inflammatory factors and normal bacterial microbiota. The efficacy of the frozen FMT group was better than that of the fresh FMT group in terms of behavior and colon length. Conclusion: FMT method supplements the gut microbiota with beneficial bacteria, such as short-chain fatty acid-producing bacteria. These bacteria can regulate intestinal function, protect the mucosal barrier and reduce harmful bacteria, thus mitigating the damage to the intestinal barrier and the associated inflammatory response, resulting in UC remission. FMT is a feasible method for treating UC, with frozen FMT having a superior therapeutic effect than that of fresh FMT.}, }
@article {pmid34332209, year = {2021}, author = {Corrie, L and Gulati, M and Vishwas, S and Kapoor, B and Singh, SK and Awasthi, A and Khursheed, R}, title = {Combination therapy of curcumin and fecal microbiota transplant: Potential treatment of polycystic ovarian syndrome.}, journal = {Medical hypotheses}, volume = {154}, number = {}, pages = {110644}, doi = {10.1016/j.mehy.2021.110644}, pmid = {34332209}, issn = {1532-2777}, abstract = {Polycystic ovarian syndrome (PCOS) is a combination of various symptoms like anovulation, hirsutism, chronic amenorrhea, infertility, obesity and polycystic ovaries. It affects over 7 million women worldwide. The current strategy to treat this disorder is based on the use of drugs that provide symptomatic relief. Most of these, however, exhibit numerous side effects and are not able to ameliorate all the signs and symptoms of PCOS. As dysbiosis is considered as one of the prime underlying causes of PCOS, restoration of eubiosis was considered as a plausible way to treat it. Bacteriotherpeutics like probiotics, synbiotics and even fecal microbiota transplant (FMT) have shown considerable effectiveness in PCOS. Of these baceteriotherapeutic options, FMT is considered to be the most holistic as it encompasses the bacteriome, virome, fungome, archaeome and even parasitome while both probiotics as well as synbiotics mainly comprise bacteria. Repeated FMT, however, is not a pragmatic option because of its inconvenience, lack of standardization, involved risk and scepticism amongst patients and physicians. If the eubiosis ushered by FMT is sustained for a long time, the repeated administrations of FMT can be avoided and maintenance therapy with any agent that can maintain the eubiotic condition can be adopted. Role of curcumin on gut microbiota is widely known. It is largely attributed to the ability of certain microbes to consume polyphenols as substrates and its positive effect on bacterial consumption of nutrients such as sugars. Based on various mechanisms and studies, a new hypothesis is being proposed wherein FMT and curcumin combination is predicted to be an effective and sustained treatment of PCOS with much lower rates of remission.}, }
@article {pmid34330600, year = {2021}, author = {Ji, Y and Tao, T and Zhang, J and Su, A and Zhao, L and Chen, H and Hu, Q}, title = {Comparison of effects on colitis-associated tumorigenesis and gut microbiota in mice between Ophiocordyceps sinensis and Cordyceps militaris.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {}, number = {}, pages = {153653}, doi = {10.1016/j.phymed.2021.153653}, pmid = {34330600}, issn = {1618-095X}, abstract = {BACKGROUND: Gut microbiota plays an indispensable role in the treatment of inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). As traditional medicinal fungi, previous studies have shown that Ophiocordyceps sinensis could better maintain intestinal health via promoting the growth of probiotics in vitro compared with Cordyceps militaris. However, the detailed pharmacological activities and clinical efficacy of O. sinensis and C. militaris are still elusive.<br><br>PURPOSE: We aimed to evaluate the different actions of O. sinensis and C. militaris on colitis-associated tumorigenesis in Azoxymethane (AOM)/Dextran Sulfate Sodium (DSS)-treated mice and explore the potential gut microbiota-dependent mechanisms.<br><br>METHODS: C57BL/6 mice (Male, 4 weeks old) were used to construct the AOM/DSS-induced CAC mice model. The mice were administered with 0.6 mg/g/d O. sinensis or C. militaris for 12 weeks. It's worth noting that fecal microbiota transplantation (FMT) and antibiotic treatment were used to investigated the complex interactions between the medicinal fungi, gut microbiota and colonic tumorigenesis.<br><br>RESULTS: O. sinensis treatment significantly increased the body weight and survival rate, reduced the number of colon tumors, improved the damage of colon epithelial tissue, restored the crypt structure and alleviate the colonic inflammation in AOM/DSS-treated mice. RT-qPCR results indicated that O. sinensis partly regulated the Wnt/β-catenin signaling via alleviating the overexpression of β-catenin, TCF4 and c-Myc genes in adjacent noncancerous tissues. Compared with C. militaris, O. sinensis showed better anti-tumor activity. Gut microbiota analysis revealed that O. sinensis reversed the decline of gut microbiota diversity and the structural disorder induced by AOM/DSS. Spearman's correlation analysis showed that O. sinensis promoted the growth of Parabacteroides goldsteinii and Bifidobacterium pseudolongum PV8-2, which were positively correlated with the anti-tumor activity and the production of SCFAs. FMT combined with antibiotic treatment showed that horizontal fecal transfer derived from O. sinensis-treated mice improved the intestinal inflammation and alleviated the colitis-associated tumorigenesis, which was consistent with the direct ingestion of O. sinensis.<br><br>CONCLUSION: O. sinensis could better attenuate colitis-associated tumorigenesis compared with C. militaris. These effects might be at least partially due to the increased abundance of probiotics, especially P. goldsteinii and B. pseudolongum PV8-2.}, }
@article {pmid34329563, year = {2021}, author = {Sehgal, K and Khanna, S}, title = {Gut microbiota: a target for intervention in obesity.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/17474124.2021.1963232}, pmid = {34329563}, issn = {1747-4132}, abstract = {INTRODUCTION: Obesity is a major public health concern with an increasing prevalence. Recent studies suggest an influence of gastrointestinal microbiota on obesity. Consequently, microbiota restoration therapies are being considered as potential management. We present data on microbiome markers and the future of microbiota therapeutics for obesity.<br><br>AREAS COVERED: We summarize the pathogenesis of obesity, relationship between gut microbiota and obesity, use of microbiota-based therapies. Data were gathered by a literature search of articles in PubMed from the date of inception till August 2020. Keywords used were 'gut microbiota,' 'gut microbiome,' 'microbiota,' 'microbiome,' 'obesity,' and 'obesity and fecal microbiota transplantation' as MeSH terms.<br><br>EXPERT OPINION: The direct relationship of gut microbiota in causing obesity needs exploration. Because of the scarcity of human studies, the utility of microbiota-based therapies as treatment remains uncertain and the use of microbiome restoration for obesity should be restricted to research settings. To evaluate the efficacy of microbiota restoration, studies using these therapies as an adjunct with diet and lifestyle should be conducted. Once relationships between bacterial strains and the human metabolic profile are determined, these strains could be cultured for transfer to obese patients. Such advancement could help in tailoring personalized therapies for obese persons.}, }
@article {pmid34328191, year = {2021}, author = {Nishikawa, H and Fukunishi, S and Asai, A and Yokohama, K and Ohama, H and Nishiguchi, S and Higuchi, K}, title = {Dysbiosis and liver diseases (Review).}, journal = {International journal of molecular medicine}, volume = {48}, number = {3}, pages = {}, doi = {10.3892/ijmm.2021.5016}, pmid = {34328191}, issn = {1791-244X}, abstract = {Dysbiosis, a qualitative and quantitative aberrancy of gut microbiota, has attracted marked attention. At present, advances in molecular biological techniques have made it possible to analyze gut microbiota at the DNA and RNA levels without culturing, and methods such as 16S ribosomal RNA targeting analysis and metagenomic analysis using next‑generation sequencers have been developed. The relationship between gut microbiota and various diseases has been extensively examined. Gut microbiota are essential for the immune system, energy intake and fat storage, and humans use them to build complex immune regulatory mechanisms and to obtain energy from food. The liver is the first organ to be nourished by the portal blood flow of intestinal origin, and liver diseases can be strongly influenced by various factors of intestinal origin, such as intestinal bacteria, bacterial components, and intestinal bacterial metabolites. Rigorous research has revealed that the composition of the gut microbiota is altered and the diversity of bacteria is reduced in liver diseases. Significance of various factors transported to the liver by portal vein blood flow from the intestine has been extensively investigated. Gut microbiota in liver disease can be associated with disease progression regardless of disease etiology and even with carcinogenesis. The relationship between gut microbiota and liver diseases (hepatitis virus‑related diseases, autoimmune liver diseases, alcoholic liver disease, non‑alcoholic fatty liver disease, non‑alcoholic steatohepatitis, liver cirrhosis and hepatocellular carcinoma) and the treatments of dysbiosis (antibiotics, prebiotics, probiotics and fecal microbiota transplantation) in liver disease are outlined based on the current evidence.}, }
@article {pmid34328058, year = {2021}, author = {Gheorghe, CE and Ritz, NL and Martin, JA and Wardill, HR and Cryan, JF and Clarke, G}, title = {Investigating causality with fecal microbiota transplantation in rodents: applications, recommendations and pitfalls.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1941711}, pmid = {34328058}, issn = {1949-0984}, abstract = {In recent years, studies investigating the role of the gut microbiota in health and diseases have increased enormously - making it essential to deepen and question the research methodology employed. Fecal microbiota transplantation (FMT) in rodent studies (either from human or animal donors) allows us to better understand the causal role of the intestinal microbiota across multiple fields. However, this technique lacks standardization and requires careful experimental design in order to obtain optimal results. By comparing several studies in which rodents are the final recipients of FMT, we summarize the common practices employed. In this review, we document the limitations of this method and highlight different parameters to be considered while designing FMT Studies. Standardizing this method is challenging, as it differs according to the research topic, but avoiding common pitfalls is feasible. Several methodological questions remain unanswered to this day and we offer a discussion on issues to be explored in future studies.}, }
@article {pmid34324703, year = {2021}, author = {Mengoni, F and Salari, V and Kosenkova, I and Tsenov, G and Donadelli, M and Malerba, G and Bertini, G and Del Gallo, F and Fabene, PF}, title = {Gut microbiota modulates seizure susceptibility.}, journal = {Epilepsia}, volume = {}, number = {}, pages = {}, doi = {10.1111/epi.17009}, pmid = {34324703}, issn = {1528-1167}, abstract = {A bulk of data suggest that the gut microbiota plays a role in a broad range of diseases, including those affecting the central nervous system. Recently, significant differences in the intestinal microbiota of patients with epilepsy, compared to healthy volunteers, have been reported in an observational study. However, an active role of the intestinal microbiota in the pathogenesis of epilepsy, through the so-called "gut-brain axis," has yet to be demonstrated. In this study, we evaluated the direct impact of microbiota transplanted from epileptic animals to healthy recipient animals, to clarify whether the microbiota from animals with epilepsy can affect the excitability of the recipients' brain by lowering seizure thresholds. Our results provide the first evidence that mice who received microbiota from epileptic animals are more prone to develop status epilepticus, compared to recipients of "healthy" microbiota, after a subclinical dose of pilocarpine, indicating a higher susceptibility to seizures. The lower thresholds for seizure activity found in this study support the hypothesis that the microbiota, through the gut-brain axis, is able to affect neuronal excitability in the brain.}, }
@article {pmid34321175, year = {2020}, author = {Yang, F and Chen, H and Gao, Y and An, N and Li, X and Pan, X and Yang, X and Tian, L and Sun, J and Xiong, X and Xing, Y}, title = {Gut microbiota-derived short-chain fatty acids and hypertension: Mechanism and treatment.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {130}, number = {}, pages = {110503}, doi = {10.1016/j.biopha.2020.110503}, pmid = {34321175}, issn = {1950-6007}, mesh = {Animals ; Disease Management ; Disease Susceptibility ; Dysbiosis ; Fatty Acids, Volatile/*metabolism ; *Gastrointestinal Microbiome ; Gene Expression Regulation ; Histones/metabolism ; Host-Pathogen Interactions ; Humans ; Hypertension/diagnosis/*etiology/*metabolism/therapy ; Receptors, G-Protein-Coupled/metabolism ; Signal Transduction ; }, abstract = {Hypertension (HTN) is an growing emerging health issue around across the world. In recent years, increasing attention has been paid to the role of dysbacteriosis in HTN and its underlying mechanism. Short-chain fatty acids (SCFAs), which are novel metabolites of intestinal flora, exert substantial regulatory effects on HTN, providing an exciting avenue for novel therapies for this disease. They function primarily by activating transmembrane G protein-coupled receptors and inhibiting histone acetylation. In this review, we discuss the mechanisms underlying the complex interaction between SCFAs and gut microbiota composition to lower blood pressure by regulating the brain-gut and kidney-gut axes, and the role of high-salt diet, immune system, oxidative stress, and inflammatory mechanism in the development of HTN. Furthermore, we also discuss the various treatment strategies for HTN, including diet, antibiotics, probiotics, fecal microflora transplantation, and traditional Chinese medicine. In conclusion, manipulation of SCFAs opens new avenues to improve treatment of HTN.}, }
@article {pmid34320242, year = {2021}, author = {Li, Y and Dong, J and Xiao, H and Wang, B and Chen, Z and Zhang, S and Jin, Y and Li, Y and Fan, S and Cui, M}, title = {Caloric restriction alleviates radiation injuries in a sex-dependent fashion.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {35}, number = {8}, pages = {e21787}, doi = {10.1096/fj.202100351RR}, pmid = {34320242}, issn = {1530-6860}, mesh = {Animals ; *Caloric Restriction ; Feces/microbiology ; Female ; Gastrointestinal Diseases/therapy ; *Gastrointestinal Microbiome ; Hematopoiesis/*radiation effects ; Inflammation/therapy ; Male ; Mice ; Mice, Inbred C57BL ; Radiation Injuries/*complications/*therapy ; Sex Factors ; Specific Pathogen-Free Organisms ; }, abstract = {Safe and effective regimens are still needed given the risk of radiation toxicity from iatrogenic irradiation. The gut microbiota plays an important role in radiation damage. Diet has emerged as a key determinant of the intestinal microbiome signature and function. In this report, we investigated whether a 30% caloric restriction (CR) diet may ameliorate radiation enteritis and hematopoietic toxicity. Experimental mice were either fed ad libitum (AL) or subjected to CR preconditioning for 10 days and then exposed to total body irradiation (TBI) or total abdominal irradiation (TAI). Gross examinations showed that short-term CR pretreatment restored hematogenic organs and improved the intestinal architecture in both male and female mice. Intriguingly, CR preconditioning mitigated radiation-induced systemic and enteric inflammation in female mice, while gut barrier function improved in irradiated males. 16S rRNA high-throughput sequencing showed that the frequency of pro-inflammatory microbes, including Helicobacter and Desulfovibrionaceae, was reduced in female mice after 10 days of CR preconditioning, while an enrichment of short-chain fatty acid (SCFA)-producing bacteria, such as Faecalibaculum, Clostridiales, and Lactobacillus, was observed in males. Using fecal microbiota transplantation (FMT) or antibiotic administration to alter the gut microbiota counteracted the short-term CR-elicited radiation tolerance of both male and female mice, further indicating that the radioprotection of a 30% CR diet depends on altering the gut microbiota. Together, our findings provide new insights into CR in clinical applications and indicate that a short-term CR diet prior to radiation modulates sex-specific gut microbiota configurations, protecting male and female mice against the side effects caused by radiation challenge.}, }
@article {pmid34319520, year = {2021}, author = {El-Sayed, A and Aleya, L and Kamel, M}, title = {Microbiota and epigenetics: promising therapeutic approaches?.}, journal = {Environmental science and pollution research international}, volume = {}, number = {}, pages = {}, pmid = {34319520}, issn = {1614-7499}, abstract = {The direct/indirect responsibility of the gut microbiome in disease induction in and outside the digestive tract is well studied. These results are usually from the overpopulation of certain species on the cost of others, interaction with beneficial microflora, interference with normal epigenetic control mechanisms, or suppression of the immune system. Consequently, it is theoretically possible to cure such disorders by rebalancing the microbiome inside our bodies. This can be achieved by changing the lifestyle pattern and diet or by supplementation with beneficial bacteria or their metabolites. Various approaches have been explored to manipulate the normal microbial inhabitants, including nutraceutical, supplementations with prebiotics, probiotics, postbiotics, synbiotics, and antibiotics, or through microbiome transplantation (fecal, skin, or vaginal microbiome transplantation). In the present review, the interaction between the microbiome and epigenetics and their role in disease induction is discussed. Possible future therapeutic approaches via the reestablishment of equilibrium in our internal micro-ecosystem are also highlighted.}, }
@article {pmid34313540, year = {2021}, author = {Trikha, SRJ and Lee, DM and Ecton, KE and Wrigley, SD and Vazquez, AR and Litwin, NS and Thomas, KN and Wei, Y and Battson, ML and Johnson, SA and Kuhn, KA and Colgan, SP and Gentile, CL and Weir, TL}, title = {Transplantation of an obesity-associated human gut microbiota to mice induces vascular dysfunction and glucose intolerance.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1940791}, pmid = {34313540}, issn = {1949-0984}, support = {R01 DK104713/DK/NIDDK NIH HHS/United States ; R01 HL144611/HL/NHLBI NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; }, abstract = {Recent preclinical data suggest that alterations in the gut microbiota may be an important factor linking obesity to vascular dysfunction, an early sign of cardiovascular disease. The purpose of this study was to begin translation of these preclinical data by examining whether vascular phenotypes in humans are transmissible through the gut microbiota. We hypothesized that germ-free mice colonized with gut microbiota from obese individuals would display diminished vascular function compared to germ-free mice receiving microbiota from lean individuals.We transplanted fecal material from obese and lean age-and sex-matched participants with disparate vascular function to germ-free mice. Using Principle Component Analysis, the microbiota of colonized mice separated by donor group along the first principle component, accounting for between 70-93% of the total variability in the dataset. The microbiota of mice receiving transplants from lean individuals was also characterized by increased alpha diversity, as well as increased relative abundance of potentially beneficial bacteria, including Bifidobacterium, Lactobacillus, and Bacteroides ovatis. Endothelium-dependent dilation, aortic pulse wave velocity and glucose tolerance were significantly altered in mice receiving microbiota from the obese donor relative to those receiving microbiota from the lean donor or those remaining germ-free.These data indicate that the obesity-associated human gut microbiota is sufficient to alter the vascular phenotype in germ-free mice in the absence of differences in body weight or dietary manipulation, and provide justification for future clinical trials to test the efficacy of microbiota-targeted therapies in the prevention or treatment of cardiovascular disease.}, }
@article {pmid34312355, year = {2021}, author = {Jo, HG and Seo, GS}, title = {[Efficacy and Safety of Fecal Microbiota Transplantation and Prospect of Microbe-based Therapies for Inflammatory Bowel Disease].}, journal = {The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi}, volume = {78}, number = {1}, pages = {31-36}, doi = {10.4166/kjg.2021.089}, pmid = {34312355}, issn = {2233-6869}, abstract = {The use of 5-ASA, immunomodulators, biologics, and small molecule drugs are the main treatment for inflammatory bowel disease (IBD), however, fecal microbiota transplantation (FMT) is also drawing attention as a treatment to improve intestinal dysbiosis by transplantaing normal human stool into patients with IBD. FMT demonstrates relatively good effects in inducing clinical remission in IBD, but unlike Clostridium difficile infection, multiple FMT can enhance the clinical effect. There are no reports of the long-term effectiveness and safety of FMT conducted in IBD yet, therefore, well-designed, prospective studies will be needed. Gut microbiota can affect inflammatory response, intestinal barrier function, and host metabolism, so microbe-based therapies are likely to be a new treatment option for IBD. The deeper the understanding of microbe products or effectors, the more likely it is to provide personalized therapy in IBD.}, }
@article {pmid34308364, year = {2020}, author = {Huang, YW and Pan, P and Echeveste, CE and Wang, HT and Oshima, K and Lin, CW and Yearsley, M and Xiao, J and Chen, J and Sun, C and Yu, J and Wang, LS}, title = {Transplanting fecal material from wild-type mice fed black raspberries alters the immune system of recipient mice.}, journal = {Food frontiers}, volume = {1}, number = {3}, pages = {253-259}, pmid = {34308364}, issn = {2643-8429}, support = {R01 CA148818/CA/NCI NIH HHS/United States ; }, abstract = {By constantly stimulating intestinal immunity, gut microbes play important regulatory roles, and their possible involvement in human physical and mental disorders beyond intestinal diseases suggests the importance of maintaining homeostasis in the gut microbiota. Both transplantation of fecal microbiota and dietary interventions have been shown to restore microbial homeostasis in recipients. In the current study with wild-type mice, we combined these two approaches to determine if transplanting fecal material from mice fed black raspberries (BRB, 5%) altered recipients' immune system. The donors received a control or 5% BRB diet, and fecal transplantation was performed every other day 15 times into recipients fed control diet. Afterward, we used flow cytometry to analyze populations of CD3+ T, CD4+ T, CD8+ T cells, and NK cells among bone marrow cells, splenocytes, and peripheral blood mononuclear cells (PBMCs) collected from the recipients. We found that BRB-fecal material that contained both fecal microbiota and their metabolites increased NK cell populations among bone marrow cells, splenocytes, and PBMCs, and raised levels of CD8+ T cells in splenocytes. Our findings suggest that fecal transplantation can modulate the immune system and might therefore be valuable for managing a range of physical and mental disorders.}, }
@article {pmid34305883, year = {2021}, author = {Malczewski, AB and Ketheesan, N and Coward, JIG and Navarro, S}, title = {Enhancing Checkpoint Inhibitor Therapy in Solid Tissue Cancers: The Role of Diet, the Microbiome &amp; Microbiome-Derived Metabolites.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {624434}, pmid = {34305883}, issn = {1664-3224}, abstract = {Host immunity plays a central role in the regulation of anti-tumour responses during checkpoint inhibitor therapy (CIT). The mechanisms involved in long lasting remission remain unclear. Animal studies have revealed that the microbiome influences the host immune response. This is supported by human studies linking a higher microbial richness and diversity with enhanced responses to CIT. This review focuses on the role of diet, the microbiome and the microbiome-derived metabolome in enhancing responses to current CIT in solid tissue cancers. The Western diet has been associated with dysbiosis, inflammation and numerous metabolic disorders. There is preliminary evidence that lifestyle factors including a high fibre diet are associated with improved responses to CIT via a potential effect on the microbiota. The mechanisms through which the microbiota may regulate long-term immunotherapy responses have yet to be determined, although bacterial-metabolites including short chain fatty acids (SCFAs) are recognized to have an impact on T cell differentiation, and may affect T effector/regulatory T cell balance. SCFAs were also shown to enhance the memory potential of activated CD8 T cells. Many therapeutic approaches including dietary manipulation and fecal transplantation are currently being explored in order to enhance immunotherapy responses. The microbiome-derived metabolome may be one means through which bacterial metabolic products can be monitored from the start of treatment and could be used to identify patients at risk of poor immunotherapy responses. The current review will discuss recent advances and bring together literature from related fields in nutrition, oncology and immunology to discuss possible means of modulating immunity to improve responses to current CIT.}, }
@article {pmid34304786, year = {2021}, author = {Singh, P and Lembo, A}, title = {Emerging Role of the Gut Microbiome in Irritable Bowel Syndrome.}, journal = {Gastroenterology clinics of North America}, volume = {50}, number = {3}, pages = {523-545}, doi = {10.1016/j.gtc.2021.03.003}, pmid = {34304786}, issn = {1558-1942}, abstract = {Advances in bioinformatics have facilitated investigation of the role of gut microbiota in patients with irritable bowel syndrome (IBS). This article describes the evidence from epidemiologic and clinical observational studies highlighting the link between IBS and gut microbiome by investigating postinfection IBS, small intestinal bacterial overgrowth, and microbial dysbiosis. It highlights the effects of gut microbiota on mechanisms implicated in the pathophysiology of IBS, including gut-brain axis, visceral hypersensitivity, motility, epithelial barrier, and immune activation. In addition, it summarizes the current evidence on microbiome-guided therapies in IBS, including probiotics, antibiotics, diet, and fecal microbiota transplant.}, }
@article {pmid34301806, year = {2021}, author = {Xie, Y and Song, L and Yang, J and Tao, T and Yu, J and Shi, J and Jin, X}, title = {Small intestinal flora graft alters fecal flora, stool, cytokines and mood status in healthy mice.}, journal = {Life science alliance}, volume = {4}, number = {9}, pages = {}, pmid = {34301806}, issn = {2575-1077}, abstract = {Fecal microbiota transplantation is widely used. Large intestinal microbiota (LIM) is more similar to fecal microbiota than small intestinal microbiota (SIM). The SIM communities are very different from those of LIM. Therefore, SIM transplantation (SIMT) and LIM transplantation (LIMT) might exert different influences. Here, healthy adult male C57Bl/6 mice received intragastric SIMT, LIMT, or sterile PBS administration. Microbiota graft samples were collected from small/large intestine of healthy mice of the same age, sex, and strain background. Compared with PBS treatment, SIMT increased pellet number, stool wet weight, and stool water percentage; induced a fecal microbiota profile shift toward the microbial composition of the SIM graft; induced a systemic anti-inflammatory cytokines profile; and ameliorated depressive-like behaviors in recipients. LIMT, however, induced merely a slight alteration in fecal microbial composition and no significant influence on the other aspects. In sum, SIMT, rather than LIMT, affected defecation features, fecal microbial composition, cytokines profile, and depressive-like behaviors in healthy mice. This study reveals the different effects of SIMT and LIMT, providing an interesting clue for further researches involving gut microbial composition change.}, }
@article {pmid34301274, year = {2021}, author = {Lin, X and Liu, Y and Ma, L and Ma, X and Shen, L and Ma, X and Chen, Z and Chen, H and Li, D and Su, Z and Chen, X}, title = {Constipation induced gut microbiota dysbiosis exacerbates experimental autoimmune encephalomyelitis in C57BL/6 mice.}, journal = {Journal of translational medicine}, volume = {19}, number = {1}, pages = {317}, pmid = {34301274}, issn = {1479-5876}, mesh = {Animals ; Constipation ; Cytokines ; Dysbiosis/complications ; *Encephalomyelitis, Autoimmune, Experimental/complications ; Female ; *Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; Quality of Life ; Th17 Cells ; }, abstract = {BACKGROUND: Constipation is a common gastrointestinal dysfunction which has a potential impact on people's immune state and their quality of life. Here we investigated the effects of constipation on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS).<br><br>METHODS: Constipation was induced by loperamide in female C57BL/6 mice. The alternations of gut microbiota, permeability of intestinal barrier and blood-brain barrier, and histopathology of colon were assessed after constipation induction. EAE was induced in the constipation mice. Fecal microbiota transplantation (FMT) was performed from constipation mice into microbiota-depleted mice. Clinical scores, histopathology of inflammation and demyelination, Treg/Th17 and Treg17/Teff17 imbalance both in the peripheral lymphatic organs and central nervous system, cytokines include TGF-β, GM-CSF, IL-10, IL-17A, IL-17F, IL-21, IL-22, and IL-23 in serum were assessed in different groups.<br><br>RESULTS: Compared with the vehicle group, the constipation mice showed gut microbiota dysbiosis, colon inflammation and injury, and increased permeability of intestinal barrier and blood-brain barrier. We found that the clinical and pathological scores of the constipation EAE mice were severer than that of the EAE mice. Compared with the EAE mice, the constipation EAE mice showed reduced percentage of Treg and Treg17 cells, increased percentage of Th17 and Teff17 cells, and decreased ratio of Treg/Th17 and Treg17/Teff17 in the spleen, inguinal lymph nodes, brain, and spinal cord. Moreover, the serum levels of TGF-β, IL-10, and IL-21 were decreased while the GM-CSF, IL-17A, IL-17F, IL-22, and IL-23 were increased in the constipation EAE mice. In addition, these pathological processes could be transferred via their gut microbiota.<br><br>CONCLUSIONS: Our results verified that constipation induced gut microbiota dysbiosis exacerbated EAE via aggravating Treg/Th17 and Treg17/Teff17 imbalance and cytokines disturbance in C57BL/6 mice.}, }
@article {pmid34295835, year = {2021}, author = {Wang, X and Tang, Q and Hou, H and Zhang, W and Li, M and Chen, D and Gu, Y and Wang, B and Hou, J and Liu, Y and Cao, H}, title = {Gut Microbiota in NSAID Enteropathy: New Insights From Inside.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {679396}, pmid = {34295835}, issn = {2235-2988}, mesh = {Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; *Gastrointestinal Microbiome ; Humans ; *Intestinal Diseases/chemically induced ; Intestinal Mucosa ; *Microbiota ; *Probiotics ; }, abstract = {As a class of the commonly used drugs in clinical practice, non-steroidal anti-inflammatory drugs (NSAIDs) can cause a series of adverse events including gastrointestinal injuries. Besides upper gastrointestinal injuries, NSAID enteropathy also attracts attention with the introduction of capsule endoscopy and double balloon enteroscopy. However, the pathogenesis of NSAID enteropathy remains to be entirely clarified. Growing evidence from basic and clinical studies presents that gut microbiota is a critical factor in NSAID enteropathy progress. We have reviewed the recent data about the interplay between gut microbiota dysbiosis and NSAID enteropathy. The chronic medication of NSAIDs could change the composition of the intestinal bacteria and aggravate bile acids cytotoxicity. Meanwhile, NSAIDs impair the intestinal barrier by inhibiting cyclooxygenase and destroying mitochondria. Subsequently, intestinal bacteria translocate into the mucosa, and then lipopolysaccharide released from gut microbiota combines to Toll-like receptor 4 and induce excessive production of nitric oxide and pro-inflammatory cytokines. Intestinal injuries present in the condition of intestinal inflammation and oxidative stress. In this paper, we also have reviewed the possible strategies of regulating gut microbiota for the management of NSAID enteropathy, including antibiotics, probiotics, prebiotics, mucosal protective agents, and fecal microbiota transplant, and we emphasized the adverse effects of proton pump inhibitors on NSAID enteropathy. Therefore, this review will provide new insights into a better understanding of gut microbiota in NSAID enteropathy.}, }
@article {pmid34289768, year = {2021}, author = {Park, SH and Lee, JH and Shin, J and Kim, JS and Cha, B and Lee, S and Kwon, KS and Shin, YW and Choi, SH}, title = {Cognitive function improvement after fecal microbiota transplantation in Alzheimer's dementia patient: a case report.}, journal = {Current medical research and opinion}, volume = {}, number = {}, pages = {1-6}, doi = {10.1080/03007995.2021.1957807}, pmid = {34289768}, issn = {1473-4877}, abstract = {After fecal microbiota transplantation (FMT) to treat Clostridioides difficile infection (CDI), cognitive improvement is noticeable, suggesting an essential association between the gut microbiome and neural function. Although it is known that the gut microbiome is linked with cognitive function, whether FMT may lead to cognitive improvement in patients with neurodegenerative disorders remains to be elucidated. We present the case of a 90-year-old woman with Alzheimer's dementia and severe CDI who underwent FMT. Cognitive function testing (Mini-Mental State Examination, Montreal Cognitive Assessment, and Clinical Dementia Rating assessment) was performed one month before FMT and one week and one month after FMT. We collected the patients' fecal samples before FMT and 3 weeks after FMT to compare the microbiota composition. The 16S rRNA gene amplicons were analyzed using the QIIME2 platform (version 2020.2) and the Phyloseq R package. The linear discriminant analysis effect size was performed to determine the taxonomic difference between pre- and post-FMT. Functional biomarker analysis using the Kruskal-Wallis H test was performed between the pre- and post-FMT. The cognitive function tests after FMT showed an improvement compared to the tests before the procedure. FMT changed the microbiota composition in recipient feces. We found that the genera were reported to be associated with cognitive function. In addition, short-chain fatty acids were found to be significantly different between before and after FMT. This finding suggests the presence of an association between the gut microbiome and cognitive function. Further, it emphasizes the need for clinical awareness regarding the effect of FMT on the brain-gut-microbiome axis and its potential as a therapy for patients with dementia.}, }
@article {pmid34286501, year = {2021}, author = {de Belvis, AG and Fratini, A and Angioletti, C and Morsella, A and Ruggeri, R and Pepe, G and Ianiro, G and Settanni, C and Gasbarrini, A and Cammarota, G}, title = {How to define a quadruple aim framework to assess value in critical pathway of the patients with Clostridioides difficile infection.}, journal = {European review for medical and pharmacological sciences}, volume = {25}, number = {13}, pages = {4597-4610}, doi = {10.26355/eurrev_202107_26252}, pmid = {34286501}, issn = {2284-0729}, abstract = {OBJECTIVE: The study aims to define the set of Key Performance Indicators (KPIs) required to assess the Value delivered by managing patients with Clostridioides difficile infection through a Critical Pathway. We used the quadruple aim Value-Based approach, and we validated the set of KPIs with the Delphi method.<br><br>MATERIALS AND METHODS: The study focuses on patients on board a Critical Pathway on Clostridioides difficile Infection and targeted towards a Fecal Microbiota Transplantation (FMT). FMT has been used to successfully treat recurrent Clostridium difficile infection. A two-round e-Delphi survey collecting data was conducted in 2019-2020 to validate the Value-Based evaluation tool. The Value-Based criteria taken into account are Clinical Outcomes, Experience of Care, Per-capita cost, Physician's burnout.<br><br>RESULTS: The two rounds led to the validation of 50 items, and four primary clinical outcomes (Mortality rate, length of stay, readmission and complications related to the illness).<br><br>CONCLUSIONS: The evaluation tool included is validated in its totality and can provide a comprehensive overview of the Value created by the Critical pathway for patients with Clostridioides difficile. We can extend the approach illustrated in this study can also to evaluate other Critical pathways.}, }
@article {pmid34282272, year = {2021}, author = {Malard, F and Lavelle, A and Battipaglia, G and Gaugler, B and Dulery, R and Brissot, E and Mediavilla, C and Jegou, S and Rolhion, N and Ledraa, T and Mohty, R and Sokol, H and Mohty, M}, title = {Impact of gut fungal and bacterial communities on the outcome of allogeneic hematopoietic cell transplantation.}, journal = {Mucosal immunology}, volume = {}, number = {}, pages = {}, pmid = {34282272}, issn = {1935-3456}, abstract = {Patients receiving allogeneic hematopoietic cell transplantation (alloHCT) were previously shown to display a bacterial gut dysbiosis; however, limited data are available regarding the role of fungal microbiota in these patients. We evaluated the bacterial and fungal composition of the fecal microbiota at day 0 of alloHCT. Higher bacterial diversity was associated with an improved overall survival (OS) and disease-free survival (DFS). While fungal diversity had no impact on patient outcomes, we observed that high versus low relative abundance of Candida albicans in alloHCT patients at day 0 was associated with a significantly lower OS, DFS and graft-versus-host-free, relapse-free survival (GRFS) (p = 0.0008, p = 0.0064 and p = 0.026, respectively). While these results are limited by low patient numbers and low fungal read counts in some samples, they suggest a potentially important role for C albicans in alloHCT.}, }
@article {pmid34281401, year = {2021}, author = {Chu, ND and Crothers, JW and Nguyen, LTT and Kearney, SM and Smith, MB and Kassam, Z and Collins, C and Xavier, R and Moses, PL and Alm, EJ}, title = {Dynamic Colonization of Microbes and Their Functions after Fecal Microbiota Transplantation for Inflammatory Bowel Disease.}, journal = {mBio}, volume = {}, number = {}, pages = {e0097521}, doi = {10.1128/mBio.00975-21}, pmid = {34281401}, issn = {2150-7511}, abstract = {For fecal microbiota transplantation (FMT) to be successful in immune diseases like inflammatory bowel disease, it is assumed that therapeutic microbes and their beneficial functions and immune interactions must colonize a recipient patient and persist in sufficient quantity and for a sufficient period of time to produce a clinical benefit. Few studies, however, have comprehensively profiled the colonization and persistence of transferred microbes along with the transfer of their microbial functions and interactions with the host immune system. Using 16S, metagenomic, and immunoglobulin A (IgA) sequencing, we analyzed hundreds of longitudinal microbiome samples from a randomized controlled trial of 12 patients with ulcerative colitis who received fecal transplant or placebo for 12 weeks. We uncovered diverse competitive dynamics among donor and patient strains, showing that persistence of transferred microbes is far from static. Indeed, one patient experienced a dramatic loss of donor bacteria 10 weeks into the trial, coinciding with a bloom of pathogenic bacteria and worsening symptoms. We evaluated the transfer of microbial functions, including desired ones, such as butyrate production, and unintended ones, such as antibiotic resistance. By profiling bacteria coated with IgA, we identified bacteria associated with inflammation and found that microbial interactions with the host immune system can be transferred across people, which could play a role in gut microbiome therapeutics for immune-related diseases. Our findings shed light on the colonization dynamics of gut microbes and their functions in the context of FMT to treat a complex disease-information that may provide a foundation for developing more-targeted therapeutics. IMPORTANCE Fecal microbiota transplantation (FMT)-transferring fecal microbes from a healthy donor to a sick patient-has shown promise for gut diseases such as inflammatory bowel disease. Unlike pharmaceuticals, however, fecal transplants are complex mixtures of living organisms, which must then interact with the microbes and immune system of the recipient. We sought to understand these interactions by tracking the microbes of 12 inflammatory bowel disease patients who received fecal transplants for 12 weeks. We uncovered a range of dynamics. For example, one patient experienced successful transfer of donor bacteria, only to lose them after 10 weeks. We similarly evaluated transfer of microbial functions, including how they interacted with the recipient's immune system. Our findings shed light on the colonization dynamics of gut microbes, as well as their functions in the context of FMT-information that may provide a critical foundation for the development of more-targeted therapeutics.}, }
@article {pmid34276224, year = {2021}, author = {Yu, C and Zhu, X and Zheng, C and Luo, Y and Wang, F and Gao, Y and Wu, H and Sun, X and Kong, X}, title = {Methyl Diet Enhanced Sepsis-Induced Mortality Through Altering Gut Microbiota.}, journal = {Journal of inflammation research}, volume = {14}, number = {}, pages = {3107-3121}, pmid = {34276224}, issn = {1178-7031}, abstract = {Introduction: Mortality of sepsis is caused by an inappropriately amplified systemic inflammatory response and bacteremia. Methyl diet has been shown to associate with greater inflammation response in different diseases. This study aimed to determine whether dietary supplementation with methyl donors affects the inflammation response and mortality in sepsis and to investigate the underlying mechanisms.<br><br>Methods: Four-week-old male C57BL/6 mice were fed with a high-methyl diet (HMD) or a regulator diet (RD) till the experiment time. Mice septic model was induced by Cecal ligation and puncture (CLP), lipopolysaccharide (LPS), or E.coli. Inflammatory cytokine was analyzed by ELISA and qRT-PCR. Immune cell infiltration was evaluated by H&amp;E and IHC. The composition of gut microbiota was determined by 16S rRNA sequencing. The effect of gut microbiota on sepsis was further verified by fecal microbiome transplantation.<br><br>Results: Our results showed that the diet riches in methyl donors exacerbated mortality, organ injury, and circulating levels of inflammatory mediators in CLP-induced septic mice model, compared to the control diet group. However, no significant differences have been observed in the inflammatory responses in the LPS-induced septic model and macrophages activation between the two groups of mice. There was a higher bacterial burden in CLP-induced HMD mice suggested that methyl diet might modulate gut microbiota. Bacterial 16S rRNA sequencing results showed that the composition of gut microbiota was altered. The high methyl donor diet reduced the abundance of Akkermansia and Lachnospiraceae, which were associated with protective effects in sepsis, in the gut. Moreover, fecal microbiome transplantation experiment showed that the transfer of feces, which obtained from high methyl diet mice, aggravated the mortality and inflammation responses in recipient mice.<br><br>Discussion: Methyl diet enhanced CLP-induced septic mortality and inflammatory responses through altering the composition of gut microbiota. This result indicated that diet-based gut microbiota may be a new therapeutic strategy for sepsis patients.}, }
@article {pmid34275058, year = {2021}, author = {Feuerstadt, P and Aroniadis, OC and Svedlund, FL and Garcia, M and Stong, L and Boules, M and Khanna, S}, title = {Heterogeneity of Randomized Controlled Trials of Fecal Microbiota Transplantation in Recurrent Clostridioides difficile Infection.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, pmid = {34275058}, issn = {1573-2568}, abstract = {INTRODUCTION: Clinical trials have demonstrated the efficacy of FMT for reduction in CDI recurrences (rCDI), but this treatment and its reporting in the literature has significant heterogeneity. Recent publications (e.g., Ramai et al. in Dig Dis Sci 2020. https://doi.org/10.1007/s10620-020-06185-7) present the clinical outcomes for different FMT methodologies. However, to understand, compare, and contextualize outcomes, this heterogeneity in methods and reporting must be understood.<br><br>METHODS: We performed a literature review of randomized controlled trials (RCTs) of FMT for rCDI to evaluate heterogeneity among trials. A methodical search between January 2010 and May 2019 of Medline, Embase, and Cochrane was conducted for studies investigating FMT in adults with rCDI. RCTs were evaluated for a variety of methodological and reporting criteria.<br><br>RESULTS: Eight RCTs were identified, wherein 14 different FMT preparations were considered (each with distinct protocols for processing, storage, administration, and dosing). Sample sizes were generally small, with only two studies performing FMT in more than 100 patients. Three studies used non-FMT controls (vancomycin), while the remaining compared FMT with differing routes of administration or formulations. Across the identified studies, there was no standardized manner for reporting the timing of the FMT procedure. All studies tracked adverse events; however, follow-up periods were limited.<br><br>CONCLUSIONS: Considerable variability exists among RCTs, with marked differences in study design, control groups, and outcome assessment. Lack of a standard-of-care control in many trials may impact reproducibility of FMT trial outcomes in patients with rCDI. Widespread use of FMT for rCDI is still investigational; therefore, these foundational studies provide opportunities to optimize future trials.}, }
@article {pmid34273490, year = {2021}, author = {Dong, S and Zhu, M and Wang, K and Zhao, X and Hu, L and Jing, W and Lu, H and Wang, S}, title = {Dihydromyricetin improves DSS-induced colitis in mice via modulation of fecal-bacteria-related bile acid metabolism.}, journal = {Pharmacological research}, volume = {171}, number = {}, pages = {105767}, doi = {10.1016/j.phrs.2021.105767}, pmid = {34273490}, issn = {1096-1186}, abstract = {Recent studies show that the nutraceutical supplement dihydromyricetin (DHM) can alleviate IBD in murine models by downregulating the inflammatory pathways. However, the molecular mechanistic link between the therapeutic efficiency of DHM, gut microbiota, and the metabolism of microbial BAs remains elusive. In this study, we explored the improvement of DHM on the dysregulated gut microbiota of mice with dextran sulfate sodium (DSS)-induced colitis. We found that DHM could markedly improve colitis symptoms, gut barrier disruption, and colonic inflammation in DSS-treated mice. In addition, bacterial 16S rDNA sequencing assay demonstrated that DHM could alleviate gut dysbiosis in mice with colitis. Furthermore, antibiotic-mediated depletion of the gut microflora and fecal microbiome transplantation (FMT) demonstrated that the therapeutic efficiency of DHM was closely associated with gut microbiota. BA-targeted metabolomics analysis revealed that DHM restored the metabolism of microbial BAs in the gastrointestinal tract during the development of colitis. DHM significantly enriched the proportion of the beneficial Lactobacillus and Akkermansia genera, which were correlated with increased gastrointestinal levels of unconjugated BAs involving chenodeoxycholic acid and lithocholic acid, enabling the BAs to activate specific receptors, such as FXR and TGR5, and maintaining intestinal integrity. Taken together, DHM could alleviate DSS-induced colitis in mice by restoring the dysregulated gut microbiota and BA metabolism, leading to improvements in intestinal barrier function and colonic inflammation. Increased microbiota-BAs-FXR/TGR5 signaling may be the potential targets of DHM in colitis. Therefore, our findings provide novel insights into the development of novel DHM-derived drugs for the management of IBD.}, }
@article {pmid34270674, year = {2021}, author = {Cappetto, CM}, title = {Correction NoticeErratum to: Successful use of early, repeat fecal microbiota transplantation for initial treatment of severe, refractory Clostridioides difficile colitis.}, journal = {American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists}, volume = {}, number = {}, pages = {}, doi = {10.1093/ajhp/zxab273}, pmid = {34270674}, issn = {1535-2900}, }
@article {pmid34267502, year = {2021}, author = {Wang, R and Chen, T and Wang, Q and Yuan, XM and Duan, ZL and Feng, ZY and Ding, Y and Bu, F and Shi, GP and Chen, YG}, title = {Total Flavone of Abelmoschus manihot Ameliorates Stress-Induced Microbial Alterations Drive Intestinal Barrier Injury in DSS Colitis.}, journal = {Drug design, development and therapy}, volume = {15}, number = {}, pages = {2999-3016}, pmid = {34267502}, issn = {1177-8881}, abstract = {Purpose: Total flavone of Abelmoschus manihot (TFA), the effective constituents extracted from Flos Abelmoschus Manihot, has been reported to inhibit inflammation. However, the effect of TFA on ulcerative colitis (UC) progression in patients with depression is unknown. The purpose of our research was to explore the anti-UC effects of TFA in the context of depression in mice with UC by regulating the gut microbiota to drive the intestinal barrier.<br><br>Methods: In this study, chronic stress (CS) and dextran sodium sulfate (DSS) were used to induce depression and UC, respectively, in C57BL/6J mice. Fecal microbiota transplantation (FMT) was used to evaluate how treating mice modeling UC and depression with TFA effected their gut microbiota.<br><br>Results: Our results showed that TFA effectively improved UC aggravated by CS. In addition, TFA treatment improved the depression-like phenotype, the disturbed gut microbiota, and the intestinal barrier function in CS mice. It is worth noting that FMT from the CS mice to the receptor group further aggravated the damage of the intestinal barrier and the disturbance of the gut microbiota in the recipient DSS mice, thus further aggravating UC, however, treatment of the intervention of TFA in the CS fecal microbiota transplant with TFA also played its therapeutic outcome.<br><br>Conclusion: Taken together, our results show that CS disrupts the gut microbiota, triggers intestinal barrier injury and aggravates DSS colitis, while TFA is a promising drug for the treatment of UC in patients with depression.}, }
@article {pmid34267042, year = {2021}, author = {Jacob, JS and Ahmed, A and Cholankeril, G}, title = {The impact of alteration in gut microbiome in the pathogenesis of nonalcoholic fatty liver disease.}, journal = {Current opinion in infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1097/QCO.0000000000000759}, pmid = {34267042}, issn = {1473-6527}, abstract = {PURPOSE OF REVIEW: We have increasing evidence that alterations of the intestinal microbiome have a strong influence on human health. Previous work has demonstrated the association between changes in the microbiome and metabolic risk factors. One related area of interest is the relationship between dysbiosis and nonalcoholic fatty liver disease (NAFLD), as the global prevalence of NAFLD, and its resultant complications, increases.<br><br>RECENT FINDINGS: In this review, we summarize the hypothesized pathophysiology of dysbiosis-mediated progression of NAFLD, including promotion of an inflammatory intestinal environment, increased intestinal permeability, endogenous ethanol production, short-chain fatty acid production, secondary bile acid metabolism, and choline depletion. We also review potential therapeutic interventions of the microbiome to slow or prevent NAFLD progression, including antibiotics, probiotics, prebiotics, fecal microbiota transplant, and farnesoid × receptor agonism.<br><br>SUMMARY: Much of the evidence supporting dysbiosis-mediated NAFLD progression has been gathered in high-quality animal trials. There remains a need for additional observational and randomized controlled trials in humans to establish causality between the suspected factors and pathogenesis of NAFLD.}, }
@article {pmid34265528, year = {2021}, author = {Yang, J and Chen, W and Sun, Y and Liu, J and Zhang, W}, title = {Effects of cadmium on organ function, gut microbiota and its metabolomics profile in adolescent rats.}, journal = {Ecotoxicology and environmental safety}, volume = {222}, number = {}, pages = {112501}, doi = {10.1016/j.ecoenv.2021.112501}, pmid = {34265528}, issn = {1090-2414}, abstract = {Cadmium (Cd) exposure in adult animals can result in multi-organ damages and gut microbiota disturbance. However, Cd's consequences on health and gut microbiota during adolescence are obscure. In the present study, three-week-old SD rats were exposed to Cd at doses of 0, 0.25, 1, and 4 mg/kg body weight for eight weeks, and the changes of liver, kidney, and ovary function, as well as gut microbiota and its metabolomics profile, were analyzed. After transplantation of fecal bacteria from the 4 mg/kg Cd-treated group into age-matched rats (4 mg/kg-Cd recipients), the organ function and inflammatory reaction were evaluated. The results indicated that Cd perturbed gut microbiota composition, significantly decreased the abundance of Prevotella and Lachnoclostridium but increased Escherichia coli_Shigella. The fecal metabolome profile was altered and was closely correlated with some specific genera. These changes were accompanied by the inflammatory response, dyslipidemia, kidney dysfunction, and abnormal estrogen level. In 4 mg/kg-Cd recipients, the serum triglyceride (TG), lipopolysaccharide (LPS), and inflammatory cytokines were increased with the expressions of IL-1β, IL-6, TNF-α genes up-regulated in liver and kidney. Overall, this study demonstrated that Cd exposure during adolescence could cause disturbance of gut microbiota, dysfunction of liver, kidney, and ovary, which may be correlated with the activation of Cd-induced inflammatory response.}, }
@article {pmid34263258, year = {2021}, author = {Shin, JH and Hays, RA and Warren, CA}, title = {Hospitalized Older Patients with Clostridioides difficile Infection Refractory to Conventional Antibiotic Therapy Benefit from Fecal Microbiota Transplant.}, journal = {Advances in geriatric medicine and research}, volume = {3}, number = {2}, pages = {}, pmid = {34263258}, support = {K08 AG064151/AG/NIA NIH HHS/United States ; R01 AI145322/AI/NIAID NIH HHS/United States ; }, abstract = {Background: Options for Clostridioides difficile infection (CDI) refractory to conventional therapy are limited. Fecal microbiota transplant (FMT) is considered safe and effective treatment for recurrent CDI and could be a treatment option for refractory CDI. We investigated the efficacy and safety of FMT in hospitalized patients who were not responding to standard treatments for CDI.<br><br>Methods: Electronic medical records of patients who received FMT inpatient for refractory CDI were reviewed as part of quality improvement efforts to evaluate safety and efficacy of FMT in inpatient setting.<br><br>Results: Between July 2014 and December 2019, 9 patients (age 60-96) received FMT for CDI as inpatient for refractory or fulminant CDI. Most (7 of 9) of these patients had pseudomembranous colitis and underwent multiple FMTs (mean 2.15, range 1 to 3). Five patients had complete resolution and one patient had diarrhea that was C. difficile-negative. There was one recurrent CDI and two deaths, one of which may have been related to FMT or CDI. Compared to recurrent CDI at diagnosis, patients with refractory CDI had higher WBC and neutrophil counts, which decreased after FMT. The overall cure rate of FMT in refractory cases was 66.7%.<br><br>Conclusions: This study shows moderate efficacy of FMT for treatment of refractory CDI although multiple FMT treatment may need to be administered in the presence of pseudomembranous colitis. Inpatient FMT may be an alternative strategy for managing refractory CDI in this population of patients who may not have any effective medical treatment available.}, }
@article {pmid34262484, year = {2021}, author = {Song, W and Sun, LY and Zhu, ZJ and Wei, L and Qu, W and Zeng, ZG and Yang, YS}, title = {Characteristics of Gut Microbiota in Children With Biliary Atresia After Liver Transplantation.}, journal = {Frontiers in physiology}, volume = {12}, number = {}, pages = {704313}, pmid = {34262484}, issn = {1664-042X}, abstract = {Background and Aims: Biliary atresia (BA) is an idiopathic neonatal cholestasis and is the most common indication in pediatric liver transplantation (LT). Previous studies have suggested that the gut microbiota (GM) in BA is disordered. However, the effect of LT on gut dysbiosis in patients with BA has not yet been elucidated.<br><br>Methods: Patients with BA (n = 16) and healthy controls (n = 10) were recruited. In the early life of children with BA, Kasai surgery is a typical procedure for restoring bile flow. According to whether BA patients had previously undergone Kasai surgery, we divided the post-LT patients into the with-Kasai group (n = 8) and non-Kasai group (n = 8). Fecal samples were collected in both the BA and the control group; among BA patients, samples were obtained again 6 months after LT. A total of 40 fecal samples were collected, of which 16 were pre-LT, 14 were post-LT (8 were with-Kasai, 6 were non-Kasai), and 10 were from the control group. Metagenomic sequencing was performed to evaluate the GM.<br><br>Results: The Kruskal-Wallis test showed a statistically significant difference in the number of genes between the pre-LT and the control group, the pre-LT and the post-LT group (P < 0.05), but no statistical difference between the post-LT and the control group. Principal coordinate analysis also showed that the microbiome structure was similar between the post-LT and control group (P > 0.05). Analysis of the GM composition showed a significant decrease in Serratia, Enterobacter, Morganella, Skunalikevirus, and Phifllikevirus while short chain fatty acid (SCFA)-producing bacteria such as Roseburia, Blautia, Clostridium, Akkermansia, and Ruminococcus were increased after LT (linear discriminant analysis > 2, P < 0.05). However, they still did not reach the normal control level. Concerning functional profiles, lipopolysaccharide metabolism, multidrug resistance, polyamine biosynthesis, GABA biosynthesis, and EHEC/EPEC pathogenicity signature were more enriched in the post-LT group compared with the control group. Prior Kasai surgery had a specific influence on the postoperative GM.<br><br>Conclusion: LT partly improved the GM in patients with BA, which provided new insight into understanding the role of LT in BA.}, }
@article {pmid34261526, year = {2021}, author = {Cooke, NCA and Bala, A and Allard, JP and Hota, S and Poutanen, S and Taylor, VH}, title = {The safety and efficacy of fecal microbiota transplantation in a population with bipolar disorder during depressive episodes: study protocol for a pilot randomized controlled trial.}, journal = {Pilot and feasibility studies}, volume = {7}, number = {1}, pages = {142}, pmid = {34261526}, issn = {2055-5784}, support = {15T-009//Stanley Medical Research Institute/ ; }, abstract = {BACKGROUND: Bipolar disorder (BD) is a chronic, debilitating illness with significant medical morbidity, often secondary to current treatments, and a high recurrence rate. This burden of disease reflects limitations in the tolerability and efficacy of current treatments. There is a compelling body of evidence linking the gut microbiota to mental illness, and while microbial manipulation via probiotic use has been studied as a therapeutic in BD, targeted trials of fecal microbiota transplantation (FMT) have not been conducted in this population.<br><br>METHODS AND DESIGN: We describe a pilot randomized controlled trial of FMT in participants with BD depression to assess the feasibility, efficacy, safety, and tolerability of this intervention. Individuals between 18 and 65 years of age will be enrolled in the study if they meet diagnostic criteria for a major depressive episode of at least moderate severity in the context of a BD diagnosis and have not responded to treatment for BD. Participants will be randomized 1:1 to receive either screened and processed donor stool (allogenic FMT) or their own stool (autologous FMT) via colonoscopy and monitored for 24 weeks post intervention. Depressive and manic symptoms, treatment acceptability, and gastrointestinal and other side effects are assessed at baseline (prior to randomization) and weekly. Stool samples to assess microbiome composition are obtained at baseline and 3 and 6 months.<br><br>DISCUSSION: Currently, FMT represents a novel therapeutic option for treating BD depression. This protocol allows for the assessment of the feasibility, efficacy, acceptability, and safety of an intervention aimed at changing the microbiome in those with BD. Results from this pilot study will guide the development of larger trials of FMT for BD depression and may give more insight into how the gut microbiome are altered in those with BD depression.<br><br>TRIAL REGISTRATION: Clinical Trials Gov NCT03279224.}, }
@article {pmid34261379, year = {2021}, author = {Baunwall, SMD and Dahlerup, JF and Engberg, JH and Erikstrup, C and Helms, M and Juel, MA and Kjeldsen, J and Nielsen, HL and Nilsson, AC and Rode, AA and Vinter-Jensen, L and Hvas, CL}, title = {Danish national guideline for the treatment of Clostridioides difficile infection and use of faecal microbiota transplantation (FMT).}, journal = {Scandinavian journal of gastroenterology}, volume = {}, number = {}, pages = {1-22}, doi = {10.1080/00365521.2021.1922749}, pmid = {34261379}, issn = {1502-7708}, abstract = {Aim: This Danish national guideline describes the treatment of adult patients with Clostridioides (formerly Clostridium) difficile (CD) infection and the use of faecal microbiota transplantation (FMT). It suggests minimum standard for implementing an FMT service.Method: Four scientific societies appointed members for a working group which conducted a systematic literature review and agreed on the text and recommendations. All clinical recommendations were evalluated for evidence level and grade of recommendation.Results: In CD infection, the use of marketed and experimental antibiotics as well as microbiota-based therapies including FMT are described. An algorithm for evaluating treatment effect is suggested. The organisation of FMT, donor recruitment and screening, laboratory preparation, clinical application and follow-up are described.Conclusion: Updated evidence for the treatment of CD infection and the use of FMT is provided.}, }
@article {pmid34261137, year = {2021}, author = {Gu, X and Lu, Q and Zhang, C and Tang, Z and Chu, L}, title = {Clinical Application and Progress of Fecal Microbiota Transplantation in Liver Diseases: A Review.}, journal = {Seminars in liver disease}, volume = {}, number = {}, pages = {}, doi = {10.1055/s-0041-1732319}, pmid = {34261137}, issn = {1098-8971}, support = {National Natural Science Foundation of China//81904129/ ; College Student Innovation Funds Project for the Hebei University of Chinese Medicine//31800952/ ; College Student Innovation Funds Project for the Hebei University of Chinese Medicine//202014432203/ ; Fundamental Research Funds for the Southeast University//3218006405/ ; Fundamental Research Funds for the Southeast University//2242019s10024/ ; }, abstract = {The human gut harbors a dense and highly diverse microbiota of approximately 1,000 bacterial species. The interaction between the host and gut bacteria strongly influences human health. Numerous evidence suggest that intestinal flora imbalance is closely associated with the development and treatment of liver diseases, including acute liver injury and chronic liver diseases (cirrhosis, autoimmune liver disease, and fatty liver). Therefore, regulating the gut microbiota is expected to be a new method for the adjuvant treatment of liver diseases. Fecal microbiota transplantation (FMT) is defined as the transplantation of gut microbiota from healthy donors to sick patients via the upper or lower gastrointestinal route to restore the normal intestinal balance. In this study, we briefly review the current research on the gut microbiota and its link to liver diseases and then summarize the evidence to elucidate the clinical application and development of FMT in liver disease treatment.}, }
@article {pmid34258417, year = {2021}, author = {Zhou, H and Sun, J and Yu, B and Liu, Z and Chen, H and He, J and Mao, X and Zheng, P and Yu, J and Luo, J and Luo, Y and Yan, H and Ge, L and Chen, D}, title = {Gut microbiota absence and transplantation affect growth and intestinal functions: An investigation in a germ-free pig model.}, journal = {Animal nutrition (Zhongguo xu mu shou yi xue hui)}, volume = {7}, number = {2}, pages = {295-304}, pmid = {34258417}, issn = {2405-6383}, abstract = {This study was conducted to investigate host-microbiota interactions and explore the effects of maternal gut microbiota transplantation on the growth and intestinal functions of newborns in a germ-free (GF) pig model. Twelve hysterectomy-derived GF Bama piglets were reared in 6 sterile isolators. Among them, 6 were considered as the GF group, and the other 6 were orally inoculated with healthy sow fecal suspension as fecal microbiota transplanted (FMT) group. Another 6 piglets from natural birth were regarded as the conventional (CV) group. The GF and FMT groups were hand-fed with Co60-γ-irradiated sterile milk powder, while the CV group was reared by lactating Bama sows. All groups were fed for 21 days. Then, all piglets and then were switched to sterile feed for another 21 days. Results showed that the growth performance, nutrient digestibility, and concentrations of short-chain fatty acids in the GF group decreased (P < 0.05). Meanwhile, the serum urea nitrogen concentration and digesta pH values in the GF group increased compared with those in the FMT and CV groups (P < 0.05). Compared with the CV group, the GF group demonstrated upregulation in the mRNA expression levels of intestinal barrier function-related genes in the small intestine (P < 0.05). In addition, the mRNA abundances of intestinal development and absorption-related genes in the small intestine and colon were higher in the GF group than in the CV and FMT groups (P < 0.05). The FMT group exhibited greater growth performance, lipase activity, and nutrient digestibility (P < 0.05), higher mRNA expression levels of intestinal development and barrier-related genes in the small intestine (P < 0.05), and lower mRNA abundances of pro-inflammatory factor in the colon and jejunum (P < 0.05) than the CV group. In conclusion, the absence of gut microbes impaired the growth and nutrient digestibility, and healthy sow gut microbiota transplantation increased the growth and nutrient digestibility and improved the intestinal development and barrier function of newborn piglets, indicating the importance of intestinal microbes for intestinal development and functions.}, }
@article {pmid34258416, year = {2021}, author = {Peng, J and Tang, Y and Huang, Y}, title = {Gut health: The results of microbial and mucosal immune interactions in pigs.}, journal = {Animal nutrition (Zhongguo xu mu shou yi xue hui)}, volume = {7}, number = {2}, pages = {282-294}, pmid = {34258416}, issn = {2405-6383}, abstract = {There are a large number of microorganisms in the porcine intestinal tract. These microorganisms and their metabolites contribute to intestinal mucosal immunity, which is of great importance to the health of the host. The host immune system can regulate the distribution and composition of intestinal microorganisms and regulate the homeostasis of intestinal flora by secreting a variety of immune effector factors, such as mucin, secretory immunoglobulin A (sIgA), regenerating islet-derived III (RegIII)γ, and defensin. Conversely, intestinal microorganisms can also promote the differentiation of immune cells including regulatory T cells (Treg) and Th17 cells through their specific components or metabolites. Studies have shown that imbalances in the intestinal flora can lead to bacterial translocation and compromised intestinal barrier function, affecting the health of the body. This review focuses on the composition of the pig intestinal flora and the characteristics of intestinal mucosal immunity, discusses the interaction mechanism between the flora and intestinal mucosal immunity, as well as the regulation through fecal microbiota transplantation (FMT), dietary nutritional composition, probiotics and prebiotics of pig intestinal microecology. Finally, this review provides insights into the relationship between intestinal microorganisms and the mucosal immune system.}, }
@article {pmid34257825, year = {2021}, author = {Gao, T and Wang, Z and Cao, J and Dong, Y and Chen, Y}, title = {Melatonin Ameliorates Corticosterone-Mediated Oxidative Stress-Induced Colitis in Sleep-Deprived Mice Involving Gut Microbiota.}, journal = {Oxidative medicine and cellular longevity}, volume = {2021}, number = {}, pages = {9981480}, pmid = {34257825}, issn = {1942-0994}, abstract = {Background: Inflammatory bowel disease (IBD) is a result of a complex interplay, making development of a specific treatment a challenging task. Corticosterone was considered a risk factor of stress relative enteritis. Our previous studies found that melatonin exerts an improvement effect in sleep deprivation (SD)- induced corticosterone overproduction and colitis. A present study further explored the mechanism whereby melatonin prevented corticosterone-mediated SD-induced colitis.<br><br>Methods: A 72-hour SD mouse model with or without melatonin supplementation and fecal microbiota transplantation (FMT) to investigate the core role of corticosterone in melatonin-mediated gut microbiota improving SD-induced colitis. Further, corticosterone-treated mice were assessed to the effect of melatonin on corticosterone-mediated gut microbiota dysbiosis-induced colitis. Meanwhile, an in vitro test studied modulatory mechanism of metabolite melatonin.<br><br>Results: SD caused an excessive corticosterone, gut microbiota disorder and colitis phenotype. Similarly, corticosterone-supplemented mice also exhibited gut microbiota dysbiosis and colitis, and the FMT from SD-mice to normal mice could restore the SD-like colitis, but no change in the corticosterone level, which suggested that corticosterone-mediated intestinal microbiota imbalance plays a central role in SD-induced colitis. Further, we demonstrated melatonin-mediated MT2 weakened GR feedback, suppressed oxidative stress, restored the intestinal microbiota and its metabolites homeostasis, and inactivated the STAT3/AP-1/NF-κB pathway-induced inflammatory response in vivo and in vitro.<br><br>Conclusions: We revealed that excessive corticosterone is a core risk factor for SD-induced colitis and provided a better understanding of the effects of melatonin, expected to be a personalized targeted therapy drug, on corticosterone-mediated gut microbiota inducing colitis.}, }
@article {pmid34252410, year = {2021}, author = {Ianiro, G and Gasbarrini, A and Cammarota, G}, title = {Evaluating donor microbiome before fecal microbiota transplantation.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2021.07.003}, pmid = {34252410}, issn = {1528-0012}, }
@article {pmid34252073, year = {2021}, author = {Verma, S and Dutta, SK and Firnberg, E and Phillips, L and Vinayek, R and Nair, PP}, title = {Identification and engraftment of new bacterial strains by shotgun metagenomic sequence analysis in patients with recurrent Clostridioides difficile infection before and after fecal microbiota transplantation and in healthy human subjects.}, journal = {PloS one}, volume = {16}, number = {7}, pages = {e0251590}, pmid = {34252073}, issn = {1932-6203}, abstract = {BACKGROUND: Recurrent Clostridioides diffícile infection (RCDI) is associated with major bacterial dysbiosis and colitis. Fecal microbiota transplantation (FMT) is a highly effective therapeutic modality for RCDI. While several studies have identified bacterial species associated with resolution of symptoms in patients, characterization of the fecal microbiome at the bacterial strain level in RCDI patients before and after FMT and healthy donors, has been lacking. The aim of this study was to examine the ability of bacterial strains from healthy donors to engraft in the gastrointestinal tract of patients with RCDI following FMT.<br><br>METHODS: Fecal samples were collected from 22 patients with RCDI before and after FMT and their corresponding healthy donors. Total DNA was extracted from each sample and analyzed by shotgun metagenomic sequencing. The Cosmos-ID analysis platform was used for taxonomic assignment of sequences and calculation of the relative abundance (RA) of bacterial species and strains. From these data, the total number of bacterial strains (BSI), Shannon diversity index, dysbiosis index (DI), and bacterial engraftment factor, were calculated for each strain.<br><br>FINDINGS: A marked reduction (p<0·0001) in the RA of total and specific bacterial strains, especially from phylum Firmicutes, was observed in RCDI patients prior to FMT. This change was associated with an increase in the DI (p<0·0001) and in pathobiont bacterial strains from phylum Proteobacteria, such as Escherichia coli O157:H7 and Klebsiella pneumoniae UCI 34. BSI was significantly lower in this group of patients as compared to healthy donors and correlated with the Shannon Index. (p<0·0001). Identification and engraftment of bacterial strains from healthy donors revealed a greater diversity and higher relative abundance of short-chain fatty acid (SCFA)-producing bacterial strains, including Lachnospiraceae bacterium 5_1_63FAA_u_t, Dorea formicigenerans ATCC 27755, Anaerostipes hadrusand others, in RCDI patients after FMT.<br><br>INTERPRETATION: These observations identify a group of SCFA-producing bacterial strains from healthy donors that engraft well in patients with RCDI following FMT and are associated with complete resolution of clinical symptoms and bacterial dysbiosis.}, }
@article {pmid34250000, year = {2021}, author = {Tokuhara, D}, title = {Role of the Gut Microbiota in Regulating Non-alcoholic Fatty Liver Disease in Children and Adolescents.}, journal = {Frontiers in nutrition}, volume = {8}, number = {}, pages = {700058}, pmid = {34250000}, issn = {2296-861X}, abstract = {Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in children and adolescents. Although obesity is the leading cause of NAFLD, the etiologies of NAFLD are multifactorial (e.g., high-fat diet, a lack of exercise, gender, maternal obesity, the antibiotic use), and each of these factors leads to dysbiosis of the gut microbiota community. The gut microbiota is a key player in the development and regulation of the gut mucosal immune system as well as the regulation of both NAFLD and obesity. Dysbiosis of the gut microbiota promotes the development of NAFLD via alteration of gut-liver homeostasis, including disruption of the gut barrier, portal transport of bacterial endotoxin (lipopolysaccharide) to the liver, altered bile acid profiles, and decreased concentrations of short-chain fatty acids. In terms of prevention and treatment, conventional approaches (e.g., dietary and exercise interventions) against obesity and NAFLD have been confirmed to recover the dysbiosis and dysbiosis-mediated altered metabolism. In addition, increased understanding of the importance of gut microbiota-mediated homeostasis in the prevention of NAFLD suggests the potential effectiveness of gut microbiota-targeted preventive and therapeutic strategies (e.g., probiotics and fecal transplantation) against NAFLD in children and adolescents. This review comprehensively summarizes our current knowledge of the gut microbiota, focusing on its interaction with NAFLD and its potential therapeutic role in obese children and adolescents with this disorder.}, }
@article {pmid34249452, year = {2021}, author = {Matsukawa, H and Iida, N and Kitamura, K and Terashima, T and Seishima, J and Makino, I and Kannon, T and Hosomichi, K and Yamashita, T and Sakai, Y and Honda, M and Yamashita, T and Mizukoshi, E and Kaneko, S}, title = {Dysbiotic gut microbiota in pancreatic cancer patients form correlation networks with the oral microbiota and prognostic factors.}, journal = {American journal of cancer research}, volume = {11}, number = {6}, pages = {3163-3175}, pmid = {34249452}, issn = {2156-6976}, abstract = {Microbiota in the gut and oral cavities of pancreatic cancer (PC) patients differ from those of healthy persons, and bacteria in PC tissues are associated with patients' prognoses. However, the species-level relationship between a dysbiotic gut, oral and cancerous microbiota, and prognostic factors remains unknown. Whole-genome sequencing was performed with fecal DNA from 24 PC patients and 18 healthy persons (HD). Microbial taxonomies, metabolic pathways, and viral presence were determined. DNA was sequenced from saliva and PC tissues, and the association between the gut, oral, and cancer microbiota and prognostic factors in PC patients was analyzed. The PC microbiota were altered from those of the healthy microbiota in terms of microbial taxonomy, pathways and viral presence. Twenty-six species differed significantly between the PC and HD microbiota. Six fecal microbes, including Klebsiella pneumoniae, were associated with an increased hazard of death. In the co-occurrence network, microbes that were abundant in PC patients were plotted close together and formed clusters with prognosis-associated microbes, including K. pneumoniae. Multiple salivary microbes were present in the co-occurrence network. Microbacterium and Stenotrophomonas were detected in the PC tissues and formed a network with the fecal and salivary microbes. The dysbiotic gut microbiota in the PC patients formed a complex network with the oral and cancerous microbiota, and gut microbes abundant in the PC patients were closely linked with poor prognostic factors in the network.}, }
@article {pmid34246956, year = {2021}, author = {Deng, L and Shi, Y and Liu, P and Wu, S and Lv, Y and Xu, H and Chen, X}, title = {GeGen QinLian decoction alleviate influenza virus infectious pneumonia through intestinal flora.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {141}, number = {}, pages = {111896}, doi = {10.1016/j.biopha.2021.111896}, pmid = {34246956}, issn = {1950-6007}, abstract = {Influenza in humans is often accompanied by gastroenteritis-like symptoms. GeGen QinLian decoction (GQD), a Chinese herb formula, has been widely used to treat infectious diarrhea for centuries and has the effect of restoring intestinal flora. Studies have also reported that GQD were used to treat patients with influenza. However, whether regulating the intestinal flora is one of the ways GQD treats influenza has not been confirmed. In present research, we conducted a systemic pharmacological study, and the results showed that GQD may acts through multiple targets and pathways. In influenza-infected mice, GQD treatment reduced mortality and lung inflammation. Most importantly, the mortality and lung inflammation were also reduced in influenza-infected mice that have undergone fecal microbiota transplantation (FMT) from GQD (FMT-GQD) treated mice. GQD treatment or FMT-GQD treatment restores the intestinal flora, resulting in an increase in Akkermansia_muciniphila, Desulfovibrio_C21_c20 and Lactobacillus_salivarius, and a decrease in Escherichia_coli. FMT-GQD treatment inhibited the NOD/RIP2/NF-κB signaling pathway in the intestine and affected the expression of downstream related inflammatory cytokines in mesenteric lymph nodes (mLNs) and serum. In addition, FMT-GQD treatment showed systemic protection by restraining the inflammatory differentiation of CD4+ T cells. In conclusion, our study shows that GQD can affect systemic immunity, at least in part, through the intestinal flora, thereby protect the mice against influenza virus infectious pneumonia.}, }
@article {pmid34238831, year = {2021}, author = {Hourigan, SK and Nicholson, MR and Kahn, SA and Kellermayer, R}, title = {Updates and Challenges in Fecal Microbiota Transplantation for Clostridioides difficile Infection in Children.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1097/MPG.0000000000003229}, pmid = {34238831}, issn = {1536-4801}, abstract = {ABSTRACT: Fecal microbiota transplantation (FMT) is currently the most effective, but loosely regulated therapy, for recurrent Clostridioides difficile infection (rCDI) in pediatrics. Over the last two years, there have been mounting challenges in the ability to provide FMT to pediatric patients. Firstly, an FDA safety alert in 2019 reported transmission of a multi-drug resistant organism from FMT donor to recipient resulting in the death of one patient. Secondly, the COVID-19 pandemic induced further safety and regulatory challenges. Biotherapeutics are promising and more readily regulated treatment options for rCDI, which may replace FMT in the near future for adults upon regulatory agency approvals. Such approvals, however, are expected to be significantly delayed for children, raising concerns for limited access to effective treatment for children with rCDI. In this commentary, we discuss the recent challenges and future directions of FMT and microbial therapeutics in children with rCDI.}, }
@article {pmid34238386, year = {2021}, author = {Bermudez-Martin, P and Becker, JAJ and Caramello, N and Fernandez, SP and Costa-Campos, R and Canaguier, J and Barbosa, S and Martinez-Gili, L and Myridakis, A and Dumas, ME and Bruneau, A and Cherbuy, C and Langella, P and Callebert, J and Launay, JM and Chabry, J and Barik, J and Le Merrer, J and Glaichenhaus, N and Davidovic, L}, title = {The microbial metabolite p-Cresol induces autistic-like behaviors in mice by remodeling the gut microbiota.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {157}, pmid = {34238386}, issn = {2049-2618}, support = {291840//EraNet NEURON/ ; MR/M50197/1/MRC_/Medical Research Council/United Kingdom ; ARD2020 Biomédicaments GPCRAb//Région Centre Val-de-Loire/ ; MabImprove//Labex/ ; MicrobiAutism//Agence Nationale de la Recherche (FR)/ ; }, mesh = {Animals ; *Autism Spectrum Disorder ; *Autistic Disorder/etiology ; Cresols ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Mice ; }, abstract = {BACKGROUND: Autism spectrum disorders (ASD) are associated with dysregulation of the microbiota-gut-brain axis, changes in microbiota composition as well as in the fecal, serum, and urine levels of microbial metabolites. Yet a causal relationship between dysregulation of the microbiota-gut-brain axis and ASD remains to be demonstrated. Here, we hypothesized that the microbial metabolite p-Cresol, which is more abundant in ASD patients compared to neurotypical individuals, could induce ASD-like behavior in mice.<br><br>RESULTS: Mice exposed to p-Cresol for 4 weeks in drinking water presented social behavior deficits, stereotypies, and perseverative behaviors, but no changes in anxiety, locomotion, or cognition. Abnormal social behavior induced by p-Cresol was associated with decreased activity of central dopamine neurons involved in the social reward circuit. Further, p-Cresol induced changes in microbiota composition and social behavior deficits could be transferred from p-Cresol-treated mice to control mice by fecal microbiota transplantation (FMT). We also showed that mice transplanted with the microbiota of p-Cresol-treated mice exhibited increased fecal p-Cresol excretion, compared to mice transplanted with the microbiota of control mice. In addition, we identified possible p-Cresol bacterial producers. Lastly, the microbiota of control mice rescued social interactions, dopamine neurons excitability, and fecal p-Cresol levels when transplanted to p-Cresol-treated mice.<br><br>CONCLUSIONS: The microbial metabolite p-Cresol induces selectively ASD core behavioral symptoms in mice. Social behavior deficits induced by p-Cresol are dependant on changes in microbiota composition. Our study paves the way for therapeutic interventions targeting the microbiota and p-Cresol production to treat patients with ASD. Video abstract.}, }
@article {pmid34238227, year = {2021}, author = {Crothers, JW and Chu, ND and Nguyen, LTT and Phillips, M and Collins, C and Fortner, K and Del Rio-Guerra, R and Lavoie, B and Callas, P and Velez, M and Cohn, A and Elliott, RJ and Wong, WF and Vo, E and Wilcox, R and Smith, M and Kassam, Z and Budd, R and Alm, EJ and Mawe, GM and Moses, PL}, title = {Daily, oral FMT for long-term maintenance therapy in ulcerative colitis: results of a single-center, prospective, randomized pilot study.}, journal = {BMC gastroenterology}, volume = {21}, number = {1}, pages = {281}, pmid = {34238227}, issn = {1471-230X}, support = {R01 DK113800/DK/NIDDK NIH HHS/United States ; P30GM118228/NH/NIH HHS/United States ; DK113800/NH/NIH HHS/United States ; }, mesh = {*Colitis, Ulcerative/therapy ; *Fecal Microbiota Transplantation ; Feces ; Humans ; Pilot Projects ; Prospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a promising new strategy in the treatment of Inflammatory Bowel Disease, but long-term delivery systems are lacking. This randomized study was designed as a safety and feasibility study of long-term FMT in subjects with mild to moderate UC using frozen, encapsulated oral FMT (cFMT).<br><br>METHODS: Subjects were randomized 1:1 to receive FMT induction by colonoscopy, followed by 12 weeks of daily oral administration of frozen encapsulated cFMT or sham therpay. Subjects were followed for 36 weeks and longitudenal clinical assessments included multiple subjective and objective markers of disease severity. Ribosomal 16S bacterial sequencing was used to assess donor-induced changes in the gut microbiota. Changes in T regulatory (Treg) and mucosal associated invariant T (MAIT) cell populations were evaluated by flow cytometry as an exploratory endpoint.<br><br>RESULTS: Twelve subjects with active UC were randomized: 6 subjects completed the full 12-week course of FMT plus cFMT, and 6 subjects received sham treatment by colonic installation and longitudinal oral placebo capules. Chronic administration of cFMT was found to be safe and well-tolerated but home storage concerns exist. Protocol adherence was high, and none of the study subjects experienced FMT-associated treatment emergent adverse events. Two subjects that received cFMT achieved clinical remission versus none in the placebo group (95% CI = 0.38-infinity, p = 0.45). cFMT was associated with sustained donor-induced shifts in fecal microbial composition. Changes in MAIT cell cytokine production were observed in cFMT recipients and correlated with treatment response.<br><br>CONCLUSION: These pilot data suggest that daily encapsulated cFMT may extend the durability of index FMT-induced changes in gut bacterial community structure and that an association between MAIT cell cytokine production and clinical response to FMT may exist in UC populations. Oral frozen encapsulated cFMT is a promising FMT delivery system and may be preferred for longterm treatment strategies in UC and other chronic diseases but further evaluations will have to address home storage concerns. Larger trials should be done to explore the benefits of cFMT and to determine its long-term impacts on the colonic microbiome.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov (NCT02390726). Registered 17 March 2015, https://clinicaltrials.gov/ct2/show/NCT02390726?term=NCT02390726&amp;draw=2&amp;rank=1 .}, }
@article {pmid34237681, year = {2021}, author = {Segal, A and Zlotnik, Y and Moyal-Atias, K and Abuhasira, R and Ifergane, G}, title = {Fecal microbiota transplant as a potential treatment for Parkinson's disease - A case series.}, journal = {Clinical neurology and neurosurgery}, volume = {207}, number = {}, pages = {106791}, doi = {10.1016/j.clineuro.2021.106791}, pmid = {34237681}, issn = {1872-6968}, abstract = {OBJECTIVE: We aimed to determine whether fecal microbiota transplant (FMT) is safe and possibly efficacious in treating constipation, motor, and non-motor symptoms in Parkinson's disease (PD) patients.<br><br>METHODS: Patients with PD, constipation and an indication for screening colonoscopy were treated with FMT. The study was conducted from December 2017 to November 2019, and clinical outcomes assessing motor, non-motor and constipation symptoms were compared at baseline (week 0) and at 2, 4, 8, 12, 16, 20, and 24 weeks after the FMT.<br><br>RESULTS: Six patients (3 men, age range 47-73, median age 52) were treated with FMT. Four weeks following the FMT, motor, non-motor and constipation scores were improved in 5 of 6 patients. At week 24, compared to before the FMT, the changes in motor scores ranged from - 13-7 points, in non-motor scores from - 2 to - 45 points, and in constipation scores from - 12-1 point. One patient had a serious adverse event requiring admission for observation only, and no adverse events were observed in all other patients.<br><br>CONCLUSIONS: In this preliminary uncontrolled case series of 6 PD patients, a treatment with donor FMT infused via colonoscopy, was safe and resulted in improvement of PD motor and non-motor symptoms, including constipation, at 6 months. Further research is needed to assess longer-term maintenance of efficacy and safety, including in large scale randomized controlled trials.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov - NCT03876327.}, }
@article {pmid34236740, year = {2021}, author = {El-Salhy, M and Hausken, T and Hatlebakk, JG}, title = {Current status of fecal microbiota transplantation for irritable bowel syndrome.}, journal = {Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society}, volume = {}, number = {}, pages = {e14157}, doi = {10.1111/nmo.14157}, pmid = {34236740}, issn = {1365-2982}, support = {40415//Helse Fonna/ ; }, abstract = {BACKGROUND: Irritable bowel syndrome (IBS) is a common gastrointestinal functional disorder. Although IBS is a benign condition, it reduces the quality of life considerably. While there is currently no effective treatment for this disorder, fecal microbiota transplantation (FMT) seems to be promising.<br><br>PURPOSE: The aim of this review was to analysis possible factors affecting the success or failure of the randomized controlled trials (RCTs) of FMT for IBS and highlighting the gaps in our knowledge that need to be filled and of sketching a possible model for successful FMT in IBS patients.<br><br>METHODS: A systematic search was conducted of literature published in English from January 2015 to December 2020 using the keywords: fecal microbiota transplantation, randomized trials, and IBS.<br><br>KEY RESULTS: Seven randomized controlled trials (RCTs) on the efficacy of FMT for IBS were found in the literature. Four of the seven RCTs found various positive effects, while the other three did not find any effect.<br><br>CONCLUSIONS AND INFERENCES: The efficacy of FMT for IBS appears to be donor-dependent. The effective (super) donor would need to have a favorable microbiota signature, and 11 clinical criteria that are known to be associated with a favorable microbiota have been suggested for selecting FMT donors for IBS. Comparing the microbiota of the effective donors with those of healthy subjects would reveal the favorable microbiota signature required for a super-donor. However, the studies reviewed were not designed to compare efficacy of different donor types. The dose of the fecal transplant is also an important factor influencing the outcome of FMT for IBS. However, further studies designed to test the effect of fecal transplant dose are needed to answer this question. Administering the fecal transplant to either the small or large intestine seems to be effective, but the optimal route of administration remains to be determined. Moreover, whether single or repeated FMT is more effective is also still unclear. A 1-year follow-up of IBS patients who received FMT showed that adverse events of abdominal pain, diarrhea, and constipation were both mild and self-limiting.}, }
@article {pmid34232990, year = {2021}, author = {Li, Y and Honda, K}, title = {Towards the development of defined microbial therapeutics.}, journal = {International immunology}, volume = {}, number = {}, pages = {}, doi = {10.1093/intimm/dxab038}, pmid = {34232990}, issn = {1460-2377}, abstract = {The collection of microorganisms living in the mammalian gastrointestinal tract, termed the gut microbiota, has been shown to have profound impacts on host health and increasingly is regarded as a viable therapeutic target. Clinical studies of fecal microbiota transplantation (FMT) have demonstrated potential efficacy of microbiota-based therapies for diseases including Clostridioides difficile infections, inflammatory bowel disease, graft-versus-host disease and cancer. However, the lack of understanding of the active ingredients and potential risks of such therapies pose challenges for clinical application. Meanwhile, efforts are being made to identify effector microbes directly associated with a given phenotype, to establish causality and to devise well-characterized microbial therapeutics for clinical use. Strategies based on defined microbial components will likely enhance the potential of microbiota-targeted therapies.}, }
@article {pmid34232137, year = {2021}, author = {Kociolek, LK and Crews, JD and Schwenk, HT}, title = {Recent advances in Clostridioides difficile infection epidemiology, diagnosis and treatment in children.}, journal = {Current opinion in infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1097/QCO.0000000000000753}, pmid = {34232137}, issn = {1473-6527}, abstract = {PURPOSE OF REVIEW: The US Centers for Disease Control and Prevention (CDC) classified Clostridioides difficile as an 'urgent' public health threat that requires 'urgent and aggressive action'. This call to action has led to new discoveries that have advanced C. difficile infection (CDI) epidemiology, diagnosis and treatment, albeit predominantly in adults. In 2017, the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America published clinical practice guidelines for both adults and children. At that time, recommendations in children were generally limited to relatively low-quality evidence.<br><br>RECENT FINDINGS: Since publication of this guidance, there have been many advancements in the understanding of CDI in children. These include better understanding of healthcare settings as uncommon sources of C. difficile acquisition in children; risk factors for recurrent and community-associated CDI; performance of diagnostic tests in children and strategies for optimizing their use; and a more rigorous evidence base for CDI treatment in children, including the first-ever randomized controlled trial of CDI treatment in children and the largest study of fecal microbiota transplantation in children.<br><br>SUMMARY: This review highlights the most recent salient advancements in paediatric CDI knowledge and practice that supplement published clinical guidance provided prior to these advancements.}, }
@article {pmid34225483, year = {2021}, author = {Matsui, M and Fukunishi, S and Nakano, T and Ueno, T and Higuchi, K and Asai, A}, title = {Ileal Bile Acid Transporter Inhibitor Improves Hepatic Steatosis by Ameliorating Gut Microbiota Dysbiosis in NAFLD Model Mice.}, journal = {mBio}, volume = {}, number = {}, pages = {e0115521}, doi = {10.1128/mBio.01155-21}, pmid = {34225483}, issn = {2150-7511}, abstract = {Nonalcoholic fatty liver disease (NAFLD), characterized by excessive fat deposition in the liver unrelated to alcohol consumption, is highly prevalent worldwide. However, effective therapeutic agents approved for NAFLD treatment are lacking. An ileal bile acid transporter inhibitor (IBATi), which represents a new mode of treatment of chronic idiopathic constipation, leads to increased delivery of bile acids to the colon. We investigated the effect of IBATi against NAFLD through modification of the gut microbiota in mice. IBATi treatment significantly suppressed body weight gain, liver dysfunction, and serum low-density lipoprotein levels and significantly decreased NAFLD activity scores in high-fat diet (HFD) mice. Treatment with IBATi ameliorated the decreased hepatic cholesterol 7-a-monooxygenase (Cyp7a1) and increased ileal fibroblast growth factor 15 (Fgf15) mRNA expression in HFD mice. Further, IBATi treatment changed the α-diversity in the gut microbiota reduced by HFD, which was analyzed in feces using 16S rRNA sequencing. To establish the mechanism underlying improvement in NAFLD induced by IBATi, we recolonized antibiotic solution-treated mice by fecal microbiome transplantation (FMT) using stool from HFD or HFD plus IBATi mice. This is the first report that fecally transplanted gut microbiota from HFD plus IBATi mice prevented hepatic steatosis caused by HFD. In conclusion, IBATi improved hepatic steatosis by ameliorating gut microbiota dysbiosis in NAFLD model mice, suggesting a potential therapeutic agent for NAFLD treatment. IMPORTANCE NAFLD is an increasingly recognized condition that may progress to liver cirrhosis and hepatocellular carcinoma, and community surveys have assessed that the prevalence is 14 to 32% worldwide. The first line of treatment for NAFLD is lifestyle modification to achieve weight reduction, particularly through diet and exercise. However, weight reduction is difficult to achieve and maintain, and pharmacological agents approved for the treatment of NAFLD are lacking. This study investigated the influence of the gut microbiota and the effect of an IBATi on NAFLD using a murine model. Treatment with IBATi significantly improved NAFLD in HFD mice. Further, fecal microbiome transplantation using stool from HFD plus IBATi mice prevented hepatic steatosis caused by HFD. Our study makes a significant contribution to the literature because the study findings suggest a potential treatment strategy for NAFLD patients by ameliorating gut microbiota dysbiosis.}, }
@article {pmid34222037, year = {2021}, author = {Tan, R and Dong, H and Chen, Z and Jin, M and Yin, J and Li, H and Shi, D and Shao, Y and Wang, H and Chen, T and Yang, D and Li, J}, title = {Intestinal Microbiota Mediates High-Fructose and High-Fat Diets to Induce Chronic Intestinal Inflammation.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {654074}, pmid = {34222037}, issn = {2235-2988}, mesh = {Animals ; *Diet, High-Fat/adverse effects ; Firmicutes ; Fructose ; *Gastrointestinal Microbiome ; Inflammation ; Mice ; Mice, Inbred C57BL ; }, abstract = {An unhealthy diet has been linked to increased incidence of chronic diseases. To investigate the relationship between diet and intestinal inflammation, mice in two experimental groups were fed on a high-fat diet or high-fructose diet, respectively. The result showed that the defecation volume of the experimental groups was significantly reduced compared with that of the control group, and the levels of pro-inflammatory cytokines (interleukin (IL)-1β and IL-6) and IgG in serum were increased significantly. In addition, inflammatory cell infiltration was observed in intestinal tissue, indicating that a high-fructose or high-fat diet can lead to constipation and inflammation. Further analysis showed that the microbial composition of the experimental groups changed significantly, including a decrease of the Bacteroidetes/Firmicutes ratio and increased levels of Bacteroides, Akkermansia, Lactobacillus, and Ruminococcus, which might be associated with inflammation. The results of pro-inflammatory metabolites analysis showed that the levels of arachidonic acid, stearic acid, and indoxylsulfuric acid were significantly increased in the experimental groups, which were related significantly to Bacteroides, Enterococcus, and Akkermansia. Meanwhile, the content of 5-hydroxytryptamine (5-HT) was significantly decreased, which might cause constipation by reducing intestinal peristalsis. Moreover, transplantation of fecal bacteria from inflammatory mice caused constipation and inflammation in normal mice, which could be relieved by feeding a normal diet. The results of the present study indicated that changes in intestinal microbiota and microbial metabolites may underlie chronic intestinal inflammation and constipation caused by high-fructose and high-fat diets.}, }
@article {pmid34221998, year = {2021}, author = {Liu, Y and Yang, C and Zhang, Z and Jiang, H}, title = {Gut Microbiota Dysbiosis Accelerates Prostate Cancer Progression Through Increased LPCAT1 Expression and Enhanced DNA Repair Pathways.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {679712}, pmid = {34221998}, issn = {2234-943X}, abstract = {Gut microbiota dysbiosis is related to cancer development and progression. Our previous study showed that Ruminococcus was more abundant in CRPC (Castration-resistant prostate cancer) than HSPC (Hormone-sensitive prostate cancer) individuals. Here, we determined the potential mechanism of microbiota dysbiosis in prostate cancer (PCa) progression. Metagenomics was used to verify the gut microbial discrepancies between CRPC and HSPC individuals. Fecal microbiota transplantation (FMT) was performed by transferring the fecal suspension of CRPC or HSPC individuals to TRAMP mice. Afterwards, the mice's prostate histopathology and gut microbiota composition were determined. Since Ruminococcus was demonstrated to correlate with phospholipid metabolism, we used lipidomics to examine the mice's fecal lipid profiles. The expression of LPCAT1 the key enzyme for phospholipid remodeling in mice prostate was also examined. Meanwhile, both microbial functions prediction and LPCAT1 GSEA analysis (Gene Set Enrichment Analysis) indicated DNA repair pathways, we further determined the expressions of RAD51 and DNA-PKcs in mice prostate. The results showed that gut Ruminococcus was significantly more abundant in CRPC individuals. FMT using CRPC feces accelerated mice's PCa progression and increased their gut Ruminococcus abundance. Majority of fecal lipids including lysophosphatidylcholine and phosphatidylcholine were upregulated in CRPC FMT treated mice, accompanied with enhanced expressions of LPCAT1, RAD51, and DNA-PKcs in mice prostate. We reported an abundant colonization of Ruminococcus in the gut of CRPC individuals and mice receiving their fecal suspensions, and revealed the promotive capability of Ruminococcus in PCa progression via upregulating LPCAT1 and DNA repair protein expressions. The bacterium and its downstream pathways may become the targets of therapies for PCa in the future.}, }
@article {pmid34220825, year = {2021}, author = {Zhao, Y and Li, X and Zhou, Y and Gao, J and Jiao, Y and Zhu, B and Wu, D and Qi, X}, title = {Safety and Efficacy of Fecal Microbiota Transplantation for Grade IV Steroid Refractory GI-GvHD Patients: Interim Results From FMT2017002 Trial.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {678476}, pmid = {34220825}, issn = {1664-3224}, abstract = {Gastrointestinal (GI) tract graft-versus-host disease (GvHD) is a major cause of post-allo-HSCT (hematopoietic stem cell transplantation) morbidity and mortality. Patients with steroid-refractory GI-GvHD have a poor prognosis and limited therapeutic options. FMT2017002 trial (#NCT03148743) was a non-randomized, open-label, phase I/II clinical study of FMT for treating patients with grade IV steroid-refractory GI-GvHD. A total of 55 patients with steroid-refractory GI-GvHD were enrolled in this study. Forty-one patients with grade IV steroid-refractory GI-GvHD were included in the final statistical analysis. Of them, 23 patients and 18 patients were assigned to the FMT group and the control group, respectively. On days 14 and 21 after FMT, clinical remission was significantly greater in the FMT group than in the control group. Within a follow-up period of 90 days, the FMT group showed a better overall survival (OS). At the end of the study, the median survival time was >539 days in the FMT group and 107 days in the control group (HR=3.51; 95% CI, 1.21-10.17; p=0.021). Both the event-free survival time (EFS) (HR=2.3, 95% CI, 0.99-5.4; p=0.08) and OS (HR=4.4, 95% CI, 1.5-13.04; p=0.008) were higher in the FMT group during the follow-up period. Overall, the mortality rate was lower in the FMT group (HR=3.97; 95% CI, 1.34-11.75; p=0.013). No differences in the occurrence of any other side effects were observed. Our data suggest that the diversity of the intestinal microbiota could be affected by allo-HSCT. Although its effectiveness and safety need further evaluation, FMT may serve as a therapeutic option for grade IV steroid-refractory GI-GvHD.<br><br>Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT03148743].}, }
@article {pmid34219519, year = {2021}, author = {Gallop, A and Weagley, J and Paracha, SU and Grossberg, G}, title = {The Role of The Gut Microbiome in Parkinson's Disease.}, journal = {Journal of geriatric psychiatry and neurology}, volume = {34}, number = {4}, pages = {253-262}, doi = {10.1177/08919887211018268}, pmid = {34219519}, issn = {0891-9887}, abstract = {The gut microbiota is known to play a role in various disease states through inflammatory, immune and endocrinologic response. Parkinson's Disease is of particular interest as gastrointestinal involvement is one of the earlier features seen in this disease. This paper examines the relationship between gut microbiota and Parkinson's Disease, which has a growing body of literature. Inflammation caused by gut dysbiosis is thought to increase a-synuclein aggregation and worsen motor and neurologic symptoms of Parkinson's disease. We discuss potential treatment and supplementation to modify the microbiota. Some of these treatments require further research before recommendations can be made, such as cord blood transplant, antibiotic use, immunomodulation and fecal microbiota transplant. Other interventions, such as increasing dietary fiber, polyphenol and fermented food intake, can be made with few risks and may have some benefit for symptom relief and speed of disease progression.}, }
@article {pmid34213510, year = {2021}, author = {Dhere, T and Tager, D and Kilakkathi, SP and Woodworth, MH and Kraft, CS}, title = {Earlier use of fecal transplant administration during hospitalization for Clostridioides difficile infectionmay improve outcome.}, journal = {European journal of gastroenterology &amp; hepatology}, volume = {33}, number = {8}, pages = {1132-1133}, doi = {10.1097/MEG.0000000000002159}, pmid = {34213510}, issn = {1473-5687}, mesh = {Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/diagnosis/therapy ; Fecal Microbiota Transplantation ; Hospitalization ; Humans ; }, }
@article {pmid34212214, year = {2021}, author = {Gupta, M and Krishan, P and Kaur, A and Arora, S and Trehanpati, N and Singh, TG and Bedi, O}, title = {Mechanistic and physiological approaches of fecal microbiota transplantation in the management of NAFLD.}, journal = {Inflammation research : official journal of the European Histamine Research Society ... [et al.]}, volume = {70}, number = {7}, pages = {765-776}, pmid = {34212214}, issn = {1420-908X}, abstract = {Non-alcoholic fatty liver disease (NAFLD) is a multifaceted disease allied with various metabolic disorders, obesity and dysbiosis. Gut microbiota plays an influential role in the pathogenesis of NAFLD and other metabolic disorders. However, recent scientific upsurge emphasizes on the utility of beneficial gut microbiota and bacteriotherapy in the management of NAFLD. Fecal microbiota transplantation (FMT) is the contemporary therapeutic approach with state-of-the-art methods for the treatment of NAFLD. Other potential therapies include probiotics and prebiotics supplements which are based on alteration of gut microbes to treat NAFLD. In this review, our major focus is on the pathological association of gut microbiota with progression of NAFLD, historical aspects and recent advances in FMT with possible intervention to combat NAFLD and its associated metabolic dysfunctions.}, }
@article {pmid34209573, year = {2021}, author = {Gopalakrishnan, V and Dozier, EA and Glover, MS and Novick, S and Ford, M and Morehouse, C and Warrener, P and Caceres, C and Hess, S and Sellman, BR and Cohen, TS}, title = {Engraftment of Bacteria after Fecal Microbiota Transplantation Is Dependent on Both Frequency of Dosing and Duration of Preparative Antibiotic Regimen.}, journal = {Microorganisms}, volume = {9}, number = {7}, pages = {}, pmid = {34209573}, issn = {2076-2607}, abstract = {The gut microbiota has emerged as a key mediator of human physiology, and germ-free mice have been essential in demonstrating a role for the microbiome in disease. Preclinical models using conventional mice offer the advantage of working with a mature immune system. However, optimal protocols for fecal microbiota transplant (FMT) engraftment in conventional mice are yet to be established. Conventional BALB/c mice were randomized to receive 3-day (3d) or 3-week (3w) antibiotic (ABX) regimen in their drinking water followed by 1 or 5-daily FMTs from a human donor. Fecal samples were collected longitudinally and characterized using 16S ribosomal RNA (rRNA) sequencing. Semi-targeted metabolomic profiling of fecal samples was also done with liquid chromatography-mass spectrometry (LC-MS). Lastly, we sought to confirm our findings in BKS mice. Recovery of baseline diversity scores were greatest in the 3d groups, driven by re-emergence of mouse commensal microbiota, whereas the most resemblance to donor microbiota was seen in the 3w + 5-FMT group. Amplicon sequence variants (ASVs) that were linked to the input material (human ASVs) engrafted to a significantly greater extent when compared to mouse ASVs in the 3-week groups but not the 3-day groups. Lastly, comparison of metabolomic profiles revealed distinct functional profiles by ABX regimen. These results indicate successful model optimization and emphasize the importance of ABX duration and frequency of FMT dosing; the most stable and reliable colonization by donor ASVs was seen in the 3wk + 5-FMT group.}, }
@article {pmid34204748, year = {2021}, author = {Paratore, M and Santopaolo, F and Cammarota, G and Pompili, M and Gasbarrini, A and Ponziani, FR}, title = {Fecal Microbiota Transplantation in Patients with HBV Infection or Other Chronic Liver Diseases: Update on Current Knowledge and Future Perspectives.}, journal = {Journal of clinical medicine}, volume = {10}, number = {12}, pages = {}, pmid = {34204748}, issn = {2077-0383}, abstract = {Liver disease and gut dysbiosis are strictly associated, and the pathophysiology of this bidirectional relationship has recently been the subject of several investigations. Growing evidence highlights the link between gut microbiota composition, impairment of the gut-liver axis, and the development or progression of liver disease. Therefore, the modulation of gut microbiota to maintain homeostasis of the gut-liver axis could represent a potential instrument to halt liver damage, modify the course of liver disease, and improve clinical outcomes. Among all the methods available to achieve this purpose, fecal microbiota transplantation (FMT) is one of the most promising, being able to directly reshape the recipient's gut microbial communities. In this review, we report the main characteristics of gut dysbiosis and its pathogenetic consequences in cirrhotic patients, discussing the emerging data on the application of FMT for liver disease in different clinical settings.}, }
@article {pmid34204274, year = {2021}, author = {Fianchi, F and Liguori, A and Gasbarrini, A and Grieco, A and Miele, L}, title = {Nonalcoholic Fatty Liver Disease (NAFLD) as Model of Gut-Liver Axis Interaction: From Pathophysiology to Potential Target of Treatment for Personalized Therapy.}, journal = {International journal of molecular sciences}, volume = {22}, number = {12}, pages = {}, pmid = {34204274}, issn = {1422-0067}, mesh = {Bile Acids and Salts/metabolism ; Biomarkers ; Disease Management ; *Disease Susceptibility ; Energy Metabolism ; Gastrointestinal Microbiome ; Gastrointestinal Tract/*metabolism/microbiology ; Humans ; Liver/*metabolism/pathology ; Non-alcoholic Fatty Liver Disease/*etiology/*metabolism/pathology/therapy ; Permeability ; Precision Medicine/methods ; *Signal Transduction ; }, abstract = {Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease worldwide, affecting both adults and children and will result, in the near future, as the leading cause of end-stage liver disease. Indeed, its prevalence is rapidly increasing, and NAFLD is becoming a major public health concern. For this reason, great efforts are needed to identify its pathogenetic factors and new therapeutic approaches. In the past decade, enormous advances understanding the gut-liver axis-the complex network of cross-talking between the gut, microbiome and liver through the portal circulation-have elucidated its role as one of the main actors in the pathogenesis of NAFLD. Indeed, evidence shows that gut microbiota is involved in the development and progression of liver steatosis, inflammation and fibrosis seen in the context of NAFLD, as well as in the process of hepatocarcinogenesis. As a result, gut microbiota is currently emerging as a non-invasive biomarker for the diagnosis of disease and for the assessment of its severity. Additionally, to its enormous diagnostic potential, gut microbiota is currently studied as a therapeutic target in NAFLD: several different approaches targeting the gut homeostasis such as antibiotics, prebiotics, probiotics, symbiotics, adsorbents, bariatric surgery and fecal microbiota transplantation are emerging as promising therapeutic options.}, }
@article {pmid34204263, year = {2021}, author = {Vacca, M and Celano, G and Lenucci, MS and Fontana, S and Forgia, FM and Minervini, F and Scarano, A and Santino, A and Dalfino, G and Gesualdo, L and De Angelis, M}, title = {In Vitro Selection of Probiotics, Prebiotics, and Antioxidants to Develop an Innovative Synbiotic (NatuREN G) and Testing Its Effect in Reducing Uremic Toxins in Fecal Batches from CKD Patients.}, journal = {Microorganisms}, volume = {9}, number = {6}, pages = {}, pmid = {34204263}, issn = {2076-2607}, support = {XUANRO4//Regione Puglia/ ; }, abstract = {We aimed to develop an innovative synbiotic formulation for use in reducing dysbiosis, uremic toxins (e.g., p-cresol and indoxyl sulfate), and, consequently, the pathognomonic features of patients with chronic kidney disease (CKD). Twenty-five probiotic strains, belonging to lactobacilli and Bifidobacterium, were tested for their ability to grow in co-culture with different vegetable (pomegranate, tomato, and grapes) sources of antioxidants and prebiotics (inulin, fructo-oligosaccharides, and β-glucans). Probiotics were selected based on the acidification rates and viable cell counts. Inulin and fructo-oligosaccharides reported the best prebiotic activity, while a pomegranate seed extract was initially chosen as antioxidant source. The investigation was also conducted in fecal batches from healthy and CKD subjects, on which metabolomic analyses (profiling volatile organic compounds and total free amino acids) were conducted. Two out of twenty-five probiotics were finally selected. After the stability tests, the selective innovative synbiotic formulation (named NatuREN G) comprised Bifidobacterium animalis BLC1, Lacticaseibacillus casei LC4P1, fructo-oligosaccharides, inulin, quercetin, resveratrol, and proanthocyanidins. Finally, NatuREN G was evaluated on fecal batches collected from CKD in which modified the viable cell densities of some cultivable bacterial patterns, increased the concentration of acetic acid and decane, while reduced the concentration of nonanoic acid, dimethyl trisulfide, and indoxyl sulfate.}, }
@article {pmid34203609, year = {2021}, author = {Pavel, FM and Vesa, CM and Gheorghe, G and Diaconu, CC and Stoicescu, M and Munteanu, MA and Babes, EE and Tit, DM and Toma, MM and Bungau, S}, title = {Highlighting the Relevance of Gut Microbiota Manipulation in Inflammatory Bowel Disease.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {11}, number = {6}, pages = {}, pmid = {34203609}, issn = {2075-4418}, abstract = {Two different conditions are included in inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC), being distinguished by chronic recurrence of gut inflammation in persons that are genetically predisposed and subjected to environmental causative factors. The normal structure of the gut microbiome and its alterations in IBD were defined in several microbial studies. An important factor in the prolonged inflammatory process in IBD is the impaired microbiome or "dysbiosis". Thus, gut microbiome management is likely to be an objective in IBD treatment. In this review, we analyzed the existing data regarding the pathophysiological/therapeutic implications of intestinal microflora in the development and evolution of IBD. Furthermore, the main effects generated by the administration of probiotics, prebiotics, fecal transplantation, and phytochemicals supplementation were analyzed regarding their potential roles in improving the clinical and biochemical status of patients suffering from Crohn's disease (CD) and ulcerative colitis (UC), and are depicted in the sections/subsections of the present paper. Data from the literature give evidence in support of probiotic and prebiotic therapy, showing effects such as improving remission rate, improving macroscopic and microscopic aspects of IBD, reducing the pro-inflammatory cytokines and interleukins, and improving the disease activity index. Therefore, the additional benefits of these therapies should not be ignored as adjuvants to medical therapy.}, }
@article {pmid34203536, year = {2021}, author = {Özdirik, B and Müller, T and Wree, A and Tacke, F and Sigal, M}, title = {The Role of Microbiota in Primary Sclerosing Cholangitis and Related Biliary Malignancies.}, journal = {International journal of molecular sciences}, volume = {22}, number = {13}, pages = {}, pmid = {34203536}, issn = {1422-0067}, support = {1983 4/1//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Animals ; Bile Duct Neoplasms/genetics/*metabolism ; Cholangiocarcinoma/genetics/metabolism ; Cholangitis, Sclerosing/genetics/*metabolism ; Gastrointestinal Microbiome/genetics/*physiology ; Humans ; Inflammatory Bowel Diseases/genetics/metabolism ; Mice ; }, abstract = {Primary sclerosing cholangitis (PSC) is an immune-related cholangiopathy characterized by biliary inflammation, cholestasis, and multifocal bile duct strictures. It is associated with high rates of progression to end-stage liver disease as well as a significant risk of cholangiocarcinoma (CCA), gallbladder cancer, and colorectal carcinoma. Currently, no effective medical treatment with an impact on the overall survival is available, and liver transplantation is the only curative treatment option. Emerging evidence indicates that gut microbiota is associated with disease pathogenesis. Several studies analyzing fecal and mucosal samples demonstrate a distinct gut microbiome in individuals with PSC compared to healthy controls and individuals with inflammatory bowel disease (IBD) without PSC. Experimental mouse and observational human data suggest that a diverse set of microbial functions may be relevant, including microbial metabolites and bacterial processing of pharmacological agents, bile acids, or dietary compounds, altogether driving the intrahepatic inflammation. Despite critical progress in this field over the past years, further functional characterization of the role of the microbiota in PSC and related malignancies is needed. In this review, we discuss the available data on the role of the gut microbiome and elucidate important insights into underlying pathogenic mechanisms and possible microbe-altering interventions.}, }
@article {pmid34202257, year = {2021}, author = {Kao, TW and Huang, CC}, title = {Recent Progress in Metabolic Syndrome Research and Therapeutics.}, journal = {International journal of molecular sciences}, volume = {22}, number = {13}, pages = {}, pmid = {34202257}, issn = {1422-0067}, support = {V109C-076//Taipei Veterans General Hospital/ ; MOST 108-2314-B-075-062-MY3//Ministry of Science and Technology, Taiwan/ ; }, mesh = {Animals ; COVID-19/pathology/virology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Metabolic Syndrome/metabolism/pathology/*therapy ; Metabolomics ; Precision Medicine ; Proteomics ; SARS-CoV-2/isolation &amp; purification ; }, abstract = {Metabolic syndrome (MetS) is a well-defined yet difficult-to-manage disease entity. Both the precipitous rise in its incidence due to contemporary lifestyles and the growing heterogeneity among affected populations present unprecedented challenges. Moreover, the predisposed risk for developing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in populations with MetS, and the viral impacts on host metabolic parameters, underscores the need to investigate this mechanism thoroughly. Recent investigations of metabolomics and proteomics have revealed not only differentially expressed substances in MetS, but also the consequences of diet consumption and physical activity on energy metabolism. These variations in metabolites, as well as protein products, also influence a wide spectrum of host characteristics, from cellular behavior to phenotype. Research on the dysregulation of gut microbiota and the resultant inflammatory status has also contributed to our understanding of the underlying pathogenic mechanisms. As for state-of-the-art therapies, advancing depictions of the bio-molecular landscape of MetS have emerged and now play a key role in individualized precision medicine. Fecal microbiota transplantation, aiming to restore the host's homeostasis, and targeting of the bile acid signaling pathway are two approaches to combatting MetS. Comprehensive molecular inquiries about MetS by omics measures are mandatory to facilitate the development of novel therapeutic modalities.}, }
@article {pmid34202210, year = {2021}, author = {Villoslada-Blanco, P and Pérez-Matute, P and Oteo, JA}, title = {Lights and Shadows of Microbiota Modulation and Cardiovascular Risk in HIV Patients.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {13}, pages = {}, pmid = {34202210}, issn = {1660-4601}, mesh = {*Cardiovascular Diseases/epidemiology/prevention &amp; control ; *HIV Infections ; Heart Disease Risk Factors ; Humans ; *Microbiota ; Risk Factors ; }, abstract = {Human immunodeficiency virus (HIV) infection is associated with premature aging and the development of aging-related comorbidities, such as cardiovascular disease (CVD). Gut microbiota (GM) disturbance is involved in these comorbidities and there is currently interest in strategies focused on modulating GM composition and/or functionality. Scientific evidence based on well-designed clinical trials is needed to support the use of prebiotics, probiotics, symbiotics, and fecal transplantation (FT) to modify the GM and reduce the incidence of CVD in HIV-infected patients. We reviewed the data obtained from three clinical trials focused on prebiotics, 25 trials using probiotics, six using symbiotics, and four using FT. None of the trials investigated whether these compounds could reduce CVD in HIV patients. The huge variability observed in the type of compound as well as the dose and duration of administration makes it difficult to adopt general recommendations and raise serious questions about their application in clinical practice.}, }
@article {pmid34199428, year = {2021}, author = {Akutko, K and Stawarski, A}, title = {Probiotics, Prebiotics and Synbiotics in Inflammatory Bowel Diseases.}, journal = {Journal of clinical medicine}, volume = {10}, number = {11}, pages = {}, pmid = {34199428}, issn = {2077-0383}, abstract = {Inflammatory bowel diseases (IBD), which include Crohn's disease (CD) and ulcerative colitis (UC), are chronic inflammatory diseases of the digestive tract with periods of remission and relapses. The etiopathogenesis of IBD is multifactorial and has not been fully understood. Hence, only symptomatic treatment of these diseases is possible. The current pharmacological treatment has variable efficacy and is associated with the risk of significant side effects. Therefore, there is a constant need to search for new types of therapies with a high safety profile. Considering that the qualitative and quantitative profile of the gastrointestinal microbiome is often different in patients with IBD than in healthy individuals, there is a need for looking for therapies aimed at restoring intestinal microbiome homeostasis. Thus, the use of strictly defined probiotics, prebiotics and synbiotics may become an alternative form of IBD therapy. There is evidence that treatment with certain probiotic strains, e.g., VSL#3 and Escherischia coli Nissle 1917, is an effective form of therapy to induce remission in patients with mild to moderate UC. So far, the effectiveness of the use of probiotics, prebiotics and synbiotics in inducing or maintaining remission in patients with CD has not been confirmed. There are also reports of possible beneficial effects of fecal microbiota transplantation (FMT) on the course of IBD, especially UC. Further, well-planned studies on a large group of patients are needed to determine the role of specific probiotic strains, prebiotics, synbiotics and FMT in the treatment of IBD in adults and in children.}, }
@article {pmid34196310, year = {2021}, author = {Ghezzi, L and Cantoni, C and Pinget, GV and Zhou, Y and Piccio, L}, title = {Targeting the gut to treat multiple sclerosis.}, journal = {The Journal of clinical investigation}, volume = {131}, number = {13}, pages = {}, pmid = {34196310}, issn = {1558-8238}, support = {R01 NS102633/NS/NINDS NIH HHS/United States ; }, abstract = {The gut-brain axis (GBA) refers to the complex interactions between the gut microbiota and the nervous, immune, and endocrine systems, together linking brain and gut functions. Perturbations of the GBA have been reported in people with multiple sclerosis (pwMS), suggesting a possible role in disease pathogenesis and making it a potential therapeutic target. While research in the area is still in its infancy, a number of studies revealed that pwMS are more likely to exhibit altered microbiota, altered levels of short chain fatty acids and secondary bile products, and increased intestinal permeability. However, specific microbes and metabolites identified across studies and cohorts vary greatly. Small clinical and preclinical trials in pwMS and mouse models, in which microbial composition was manipulated through the use of antibiotics, fecal microbiota transplantation, and probiotic supplements, have provided promising outcomes in preventing CNS inflammation. However, results are not always consistent, and large-scale randomized controlled trials are lacking. Herein, we give an overview of how the GBA could contribute to MS pathogenesis, examine the different approaches tested to modulate the GBA, and discuss how they may impact neuroinflammation and demyelination in the CNS.}, }
@article {pmid34196224, year = {2021}, author = {Long, D and Merlin, D}, title = {Micro- and nanotechnological delivery platforms for treatment of dysbiosis-related inflammatory bowel disease.}, journal = {Nanomedicine (London, England)}, volume = {16}, number = {20}, pages = {1741-1745}, pmid = {34196224}, issn = {1748-6963}, support = {BX002526, BX004476//U.S. Department of Veterans Affairs/ ; I01 BX002526/BX/BLRD VA/United States ; R01 DK107739/DK/NIDDK NIH HHS/United States ; #689659//Research Fellowship Award from the Crohn's and Colitis Foundation of America/ ; IK6 BX004476/BX/BLRD VA/United States ; RO1-DK-107739, RO1-DK-116306/DK/NIDDK NIH HHS/United States ; R01 DK116306/DK/NIDDK NIH HHS/United States ; }, mesh = {*Colitis ; Dysbiosis/drug therapy ; Humans ; *Inflammatory Bowel Diseases/drug therapy ; }, }
@article {pmid34191698, year = {2021}, author = {Wang, X and Liang, Z and Wang, S and Ma, D and Zhu, M and Feng, J}, title = {Role of Gut Microbiota in Multiple Sclerosis and Potential Therapeutic Implications.}, journal = {Current neuropharmacology}, volume = {}, number = {}, pages = {}, doi = {10.2174/1570159X19666210629145351}, pmid = {34191698}, issn = {1875-6190}, abstract = {The role of gut microbiota in health and diseases has been receiving increased attention recently. Emerging evidence from previous studies on the gut-microbiota-brain axis highlighted the importance of gut microbiota in neurological disorders. Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS) resulting from T-cell-driven, myelin-directed autoimmunity. The dysbiosis of gut microbiota in MS patients has been reported in published research studies, indicating that gut microbiota plays an important role in the pathogenesis of MS. Gut microbiota has also been reported to influence the initiation of disease and severity of experimental autoimmune encephalomyelitis, which is the animal model of MS. However, the underlying mechanisms of gut microbiota involvement in the pathogenesis of MS remain unclear. Therefore, in this review, we summerized the potential mechanisms for gut microbiota involvement in the pathogenesis of MS, including increasing the permeability of the intestinal barrier, initiating an autoimmune response, disrupting the blood-brain barrier integrity, and contributing to chronic inflammation. The possibility for gut microbiota as a target for MS therapy has also been discussed. This review provides new insight into understanding the role of gut microbiota in neurological and inflammatory diseases.}, }
@article {pmid34190675, year = {2021}, author = {Bibbò, S and Ianiro, G and Giambò, F and Settanni, CR and Cammarota, G and Gasbarrini, A}, title = {Role of gut microbiome on immunotherapy efficacy in melanoma.}, journal = {Human vaccines &amp; immunotherapeutics}, volume = {}, number = {}, pages = {1-6}, doi = {10.1080/21645515.2021.1926759}, pmid = {34190675}, issn = {2164-554X}, abstract = {The gut microbiota is considered a key component in many aspects of cancer pathophysiology and response to therapy. In particular, in recent years intriguing evidences has been emerging regarding the role of the intestinal microbiota in the response to immunotherapy and in promoting the development of adverse events, such as colitis. For this reason, studies are being carried out both on pre-clinical models and on humans to study how to predict the response to immunotherapy through the study of the microbiota or how to improve its clinical response through modulation. Promising data have recently been reported through modulation by probiotics or prebiotics, and in particular by fecal microbiota transplantation. The aim of this review is to analyze the evidence regarding the role of the microbiota in immunotherapy with a particular focus on melanoma.}, }
@article {pmid34186487, year = {2021}, author = {Wilson, BC and Butler, ÉM and Grigg, CP and Derraik, JGB and Chiavaroli, V and Walker, N and Thampi, S and Creagh, C and Reynolds, AJ and Vatanen, T and O'Sullivan, JM and Cutfield, WS}, title = {Oral administration of maternal vaginal microbes at birth to restore gut microbiome development in infants born by caesarean section: A pilot randomised placebo-controlled trial.}, journal = {EBioMedicine}, volume = {69}, number = {}, pages = {103443}, doi = {10.1016/j.ebiom.2021.103443}, pmid = {34186487}, issn = {2352-3964}, mesh = {Administration, Oral ; Adult ; Bacteroides/pathogenicity ; Cesarean Section/*adverse effects ; Fecal Microbiota Transplantation/adverse effects/*methods ; Female ; *Gastrointestinal Microbiome ; Humans ; Infant, Newborn ; Infant, Newborn, Diseases/etiology/*microbiology/prevention &amp; control ; Male ; Vagina/*microbiology ; }, abstract = {BACKGROUND: Birth by caesarean section (CS) is associated with aberrant gut microbiome development and greater disease susceptibility later in life. We investigated whether oral administration of maternal vaginal microbiota to infants born by CS could restore their gut microbiome development in a pilot single-blinded, randomised placebo-controlled trial (Australian New Zealand Clinical Trials Registry, ACTRN12618000339257).<br><br>METHODS: Pregnant women scheduled for a CS underwent comprehensive antenatal pathogen screening. At birth, healthy neonates were randomised to receive a 3 ml solution of either maternal vaginal microbes (CS-seeded, n = 12) or sterile water (CS-placebo, n = 13). Vaginally-born neonates were used as the reference control (VB, n = 22). Clinical assessments occurred within the first 2 h of birth, and at 1 month and 3 months of age. Infant stool samples and maternal vaginal extracts from CS women underwent shotgun metagenomic sequencing. The primary outcome was gut microbiome composition at 1 month of age. Secondary outcomes included maternal strain engraftment, functional potential of the gut microbiome, anthropometry, body composition, and adverse events.<br><br>FINDINGS: Despite the presence of viable microbial cells within transplant solutions, there were no observed differences in gut microbiome composition or functional potential between CS-seeded and CS-placebo infants at 1 month or 3 months of age. Both CS groups displayed the characteristic signature of low Bacteroides abundance, which contributed to a number of biosynthesis pathways being underrepresented when compared with VB microbiomes. Maternal vaginal strain engraftment was rare. Vaginal seeding had no observed effects on anthropometry or body composition. There were no serious adverse events associated with treatment.<br><br>INTERPRETATION: Our pilot findings question the value of vaginal seeding given that oral administration of maternal vaginal microbiota did not alter early gut microbiome development in CS-born infants. The limited colonisation of maternal vaginal strains suggest that other maternal sources, such as the perianal area, may play a larger role in seeding the neonatal gut microbiome.<br><br>FUNDING: Health Research Council of New Zealand, A Better Start - National Science Challenge.}, }
@article {pmid34182544, year = {2021}, author = {Liu, M and Song, S and Chen, Q and Sun, J and Chu, W and Zhang, Y and Ji, F}, title = {Gut microbiota mediates cognitive impairment in young mice after multiple neonatal exposures to sevoflurane.}, journal = {Aging}, volume = {13}, number = {12}, pages = {16733-16748}, pmid = {34182544}, issn = {1945-4589}, mesh = {Anesthesia ; Animals ; Anti-Bacterial Agents/pharmacology ; Behavior, Animal ; Cognitive Dysfunction/*microbiology ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome/drug effects ; Germ-Free Life ; Mice, Inbred C57BL ; Morris Water Maze Test ; Pregnancy ; Prenatal Exposure Delayed Effects/*microbiology ; Sevoflurane/*adverse effects ; }, abstract = {Multiple exposures to anesthesia may increase the risk of cognitive impairment in young children. However, the mechanisms underlying this neurodevelopmental disorder remain elusive. In this study, we investigated alteration of the gut microbiota after multiple neonatal exposures to the anesthetic sevoflurane and the potential role of microbiota alteration on cognitive impairment using a young mice model. Multiple neonatal sevoflurane exposures resulted in obvious cognitive impairment symptoms and altered gut microbiota composition. Fecal transplantation experiments confirmed that alteration of the microbiota was responsible for the cognitive disorders in young mice. Microbiota profiling analysis identified microbial taxa that showed consistent differential abundance before and after fecal microbiota transplantation. Several of the differentially abundant taxa are associated with memory and/or health of the host, such as species of Streptococcus, Lachnospiraceae, and Pseudoflavonifractor. The results reveal that abnormal composition of the gut microbiota is a risk factor for cognitive impairment in young mice after multiple neonatal exposures to sevoflurane and provide insight into a potential therapeutic strategy for sevoflurane-related neurotoxicity.}, }
@article {pmid34179058, year = {2021}, author = {Yu, Y and Cao, Y and Huang, W and Liu, Y and Lu, Y and Zhao, J}, title = {β-Sitosterol Ameliorates Endometrium Receptivity in PCOS-Like Mice: The Mediation of Gut Microbiota.}, journal = {Frontiers in nutrition}, volume = {8}, number = {}, pages = {667130}, pmid = {34179058}, issn = {2296-861X}, abstract = {Background: Polycystic ovary syndrome (PCOS), one of the most common endocrine diseases in women of childbearing age, has been found to be accompanied by changes in the gut microbiota. The Bu Shen Yang Xue formula (BSYXF) is a traditional Chinese medicine widely used for the treatment of PCOS. This study aimed to investigate whether the protective effects of β-sitosterol, the main active ingredient of BSYXF, on PCOS was mediated by regulating gut microbiota. Methods: The presence of β-sitosterol in BSYXF was detected by liquid chromatography-mass spectrometry. The PCOS-like mouse model was induced by dehydroepiandrosterone. The fecal supernatant of β-sitosterol-treated mice was prepared for fecal microbiota transplantation (FMT). Body weight and wet weight of the uterus and ovary of the mice were recorded for organ index calculation. Hematoxylin and eosin stain was used to assess the endometrial morphology and microenvironment changes. Expression of endometrial receptivity markers cyclooxygenase-2 (COX-2), Integrin ανβ3, leukemia inhibitory factor (LIF), and homeobox A10 (HOXA10) in the endometrium were determined by immunohistochemistry and western blot analysis. Enzyme-linked immunosorbent assay was employed to detect the expression of follicle stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), and testosterone (T) in the serum. The diversity of gut microbiota was examined by 16S rDNA gene sequencing. Results: With the treatment of β-sitosterol and β-sitosterol-FMT, the uterine index of PCOS-like mice increased, the ovarian index decreased, levels of COX-2, LH and T decreased, and levels of Integrin ανβ3, LIF, HOXA10, FSH, and P increased. Under β-sitosterol treatment, the structure of the gut microbiota in PCOS-like mice was also changed. Conclusion: β-sitosterol regulates the endometrial receptivity of PCOS and harmonizes the sex hormone balance, which may be related to the changes in the structure and composition of gut microbiota, thus affecting the pathological process of PCOS.}, }
@article {pmid34178927, year = {2021}, author = {Vedala, K and Sobash, P and Shah, P and Kamoga, GR}, title = {Does Fecal Microbiota Transplant Have a Role in Treating Recurrent Clostridioides difficile Infection in Rural Hospitals?.}, journal = {Frontiers in public health}, volume = {9}, number = {}, pages = {670941}, pmid = {34178927}, issn = {2296-2565}, mesh = {Clostridioides ; *Clostridioides difficile ; Hospitals, Rural ; Humans ; *Microbiota ; Recurrence ; Retrospective Studies ; Treatment Outcome ; }, abstract = {Clostridioides difficile infection possesses a significant economical burden, specifically in the inpatient and rural settings. Fecal Microbiota Transplant has been used for treatment of recurrent Clostridioides difficile but its utility is limited by current guidelines and resources. We conducted a retrospective chart review to evaluate the financial benefit of using Fecal Microbiota Transplant after first recurrence of Clostridioides difficile infection. We found that while its use was restricted, on average Fecal Microbiota Transplant can save $11,603.49 per patient. In conclusion, our study shows that using Fecal Microbiota Transplant could prove to be economically beneficial in treating recurrent CDI in rural hospitals.}, }
@article {pmid34177852, year = {2021}, author = {Ma, X and Zhang, Y and Xu, T and Qian, M and Yang, Z and Zhan, X and Han, X}, title = {Early-Life Intervention Using Exogenous Fecal Microbiota Alleviates Gut Injury and Reduce Inflammation Caused by Weaning Stress in Piglets.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {671683}, pmid = {34177852}, issn = {1664-302X}, abstract = {Fecal microbiota transplantation (FMT) could shape the structure of intestinal microbiota in animals. This study was conducted to explore the changes that happen in the structure and function of microbiota caused by weaning stress, and whether early-life FMT could alleviate weaning stress through modifying intestinal microbiota in weaned piglets. Diarrheal (D) and healthy (H) weaned piglets were observed, and in the same farm, a total of nine litters newborn piglets were randomly allocated to three groups: sucking normally (S), weaned at 21 d (W), and early-life FMT + weaned at 21 d (FW). The results demonstrated that differences of fecal microbiota existed in group D and H. Early-life FMT significantly decreased diarrhea incidence of weaned piglets. Intestinal morphology and integrity were improved in the FW group. Both ZO-1 and occludin (tight junction proteins) of jejunum were greatly enhanced, while the zonulin expression was significantly down-regulated through early-life FMT. The expression of IL-6 and TNF-α (intestinal mucosal inflammatory cytokines) were down-regulated, while IL-10 (anti-inflammatory cytokines) was up-regulated by early-life FMT. In addition, early-life FMT increased the variety of the intestinal microbial population and the relative amounts of some beneficial bacteria such as Spirochaetes, Akkermansia, and Alistipes. Functional alteration of the intestinal microbiota revealed that lipid biosynthesis and aminoacyl-tRNA biosynthesis were enriched in the FW group. These findings suggested that alteration of the microbiota network caused by weaning stress induced diarrhea, and early-life FMT alleviated weaning stress in piglets, which was characterized by decreased diarrhea incidence, improved intestinal morphology, reduced intestinal inflammation, and modified intestinal bacterial composition and function.}, }
@article {pmid34177842, year = {2021}, author = {Koopen, AM and Almeida, EL and Attaye, I and Witjes, JJ and Rampanelli, E and Majait, S and Kemper, M and Levels, JHM and Schimmel, AWM and Herrema, H and Scheithauer, TPM and Frei, W and Dragsted, L and Hartmann, B and Holst, JJ and O'Toole, PW and Groen, AK and Nieuwdorp, M}, title = {Effect of Fecal Microbiota Transplantation Combined With Mediterranean Diet on Insulin Sensitivity in Subjects With Metabolic Syndrome.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {662159}, pmid = {34177842}, issn = {1664-302X}, abstract = {Background: Recent studies demonstrate that a Mediterranean diet has beneficial metabolic effects in metabolic syndrome subjects. Since we have shown that fecal microbiota transplantation (FMT) from lean donors exerts beneficial effects on insulin sensitivity, in the present trial, we investigated the potential synergistic effects on insulin sensitivity of combining a Mediterranean diet with donor FMT in subjects with metabolic syndrome.<br><br>Design: Twenty-four male subjects with metabolic syndrome were put on a Mediterranean diet and after a 2-week run-in phase, the subjects were randomized to either lean donor (n = 12) or autologous (n = 12) FMT. Changes in the gut microbiota composition and bacterial strain engraftment after the 2-week dietary regimens and 6 weeks post-FMT were the primary endpoints. The secondary objectives were changes in glucose fluxes (both hepatic and peripheral insulin sensitivity), postprandial plasma incretin (GLP-1) levels, subcutaneous adipose tissue inflammation, and plasma metabolites.<br><br>Results: Consumption of the Mediterranean diet resulted in a reduction in body weight, HOMA-IR, and lipid levels. However, no large synergistic effects of combining the diet with lean donor FMT were seen on the gut microbiota diversity after 6 weeks. Although we did observe changes in specific bacterial species and plasma metabolites, no significant beneficial effects on glucose fluxes, postprandial incretins, or subcutaneous adipose tissue inflammation were detected.<br><br>Conclusions: In this small pilot randomized controlled trial, no synergistic beneficial metabolic effects of combining a Mediterranean diet with lean donor FMT on glucose metabolism were achieved. However, we observed engraftment of specific bacterial species. Future trials are warranted to test the combination of other microbial interventions and diets in metabolic syndrome.}, }
@article {pmid34176888, year = {2021}, author = {Feng, J and Tang, YN and Zhou, LX and Pan, JS}, title = {Standardized Nursing Procedures for Fecal Microbiota Transplantation via Upper Endoscopy.}, journal = {Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates}, volume = {}, number = {}, pages = {}, doi = {10.1097/SGA.0000000000000577}, pmid = {34176888}, issn = {1538-9766}, abstract = {Fecal microbiota transplantation is an emerging treatment option that lacks a standardized nursing procedure. In our department, fecal microbiota transplantation has been undertaken to treat chronic hepatitis B and inflammatory bowel diseases since 2015. The fecal microbiota transplantation process involves various nursing measures that are critical for the successful completion of the procedures. In our center, a set of standardized nursing procedures has been established and has proved effective and operable. Standardized nursing procedures enhance the efficacy of fecal microbiota transplantation and alleviate the risk of treatment-related complications.}, }
@article {pmid34175104, year = {2021}, author = {Khanna, S}, title = {My Treatment Approach to Clostridioides difficile Infection.}, journal = {Mayo Clinic proceedings}, volume = {96}, number = {8}, pages = {2192-2204}, doi = {10.1016/j.mayocp.2021.03.033}, pmid = {34175104}, issn = {1942-5546}, abstract = {Clostridioides difficile infection is the most common cause of infectious diarrhea in hospitals with an increasing incidence in the community. Clinical presentation of C difficile infection ranges from diarrhea manageable in the outpatient setting to fulminant infection requiring intensive care admission. There have been significant advances in the management of primary and recurrent C difficile infection including diagnostics, newer antibiotics, antibody treatments, and microbiome restoration therapies. Because of the risk of clinical false-positive results with the polymerase chain reaction test, a two-step assay combining an enzyme immune assay for glutamate dehydrogenase and the C difficile toxin is being used. Cost permitting, I treat a first episode of C difficile infection preferably with fidaxomicin over vancomycin but not metronidazole. The most common complication after C difficile infection is recurrence. I manage a first recurrence with a vancomycin taper and pulse or fidaxomicin and recommend a single dose of intravenous bezlotoxumab (a monoclonal antibody against the toxin B) to reduce recurrence rates for those patients at high risk. Patients with multiply recurrent C difficile infection are managed with a course of antibiotics such as vancomycin or fidaxomicin followed by microbiota restoration. The success of fecal microbiota transplantation is greater than 85%, compared with the 40% to 50% success rate of antibiotics in this situation. Fecal microbiota transplantation is heterogeneous and has rare but serious risks such as transmission of infections. Standardized microbiota restoration therapies are in clinical development and have completed phase III clinical trials. This review answers common clinical questions in the management of C difficile infection.}, }
@article {pmid34173726, year = {2021}, author = {Tan, Q and Orsso, CE and Deehan, EC and Kung, JY and Tun, HM and Wine, E and Madsen, KL and Zwaigenbaum, L and Haqq, AM}, title = {Probiotics, prebiotics, synbiotics, and fecal microbiota transplantation in the treatment of behavioral symptoms of autism spectrum disorder: A systematic review.}, journal = {Autism research : official journal of the International Society for Autism Research}, volume = {}, number = {}, pages = {}, doi = {10.1002/aur.2560}, pmid = {34173726}, issn = {1939-3806}, abstract = {The emerging role of a microbiota-gut-brain axis in autism spectrum disorder (ASD) suggests that modulating gut microbial composition may offer a tractable approach to addressing the lifelong challenges of ASD. The aim of this systematic review was to provide an overview and critically evaluate the current evidence on the efficacy and safety of probiotic, prebiotic, synbiotic, and fecal microbiota transplantation therapies for core and co-occurring behavioral symptoms in individuals with ASD. Comprehensive searches of MEDLINE, EMBASE, Scopus, Web of Science Core Collection, Cochrane Library, and Google Scholar were performed from inception to March 5, 2020, and two update searches were completed on October 25, 2020, and April 22, 2021, respectively. A total of 4306 publications were identified, of which 14 articles met the inclusion criteria. Data were extracted independently by two reviewers using a preconstructed form. Results of probiotic studies do not confirm the supposed beneficial effect of probiotics on ASD, whereas prebiotics and synbiotic combinations appear to be efficacious in selective behavioral symptoms. Evidence of the efficacy of fecal microbiota transplantation in ASD is still scarce but supports further research. Overall, the current evidence base to suggest beneficial effects of these modalities in ASD is limited and inconclusive. More clinical trials are currently looking at the use of microbial-based therapies in ASD. With a robust double-blind randomized controlled protocol to investigate the efficacy, these trials should provide significant and definitive results. LAY SUMMARY: There is a link between altered gut bacteria and autism spectrum disorder. Some people believe that modulating bacterial composition in the gut may help reduce autism symptoms, but evidence from human studies suggesting beneficial effects of probiotic, prebiotic, and combination thereof as well as fecal transplants in autism spectrum disorder is limited and inconclusive. Current data should not encourage use of these modalities. Further clinical studies are needed.}, }
@article {pmid34172092, year = {2021}, author = {Zheng, H and Xu, P and Jiang, Q and Xu, Q and Zheng, Y and Yan, J and Ji, H and Ning, J and Zhang, X and Li, C and Zhang, L and Li, Y and Li, X and Song, W and Gao, H}, title = {Depletion of acetate-producing bacteria from the gut microbiota facilitates cognitive impairment through the gut-brain neural mechanism in diabetic mice.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {145}, pmid = {34172092}, issn = {2049-2618}, support = {21974096//National Natural Science Foundation of China/ ; 22074106//National Natural Science Foundation of China/ ; 81771386//National Natural Science Foundation of China/ ; 2018R52052//Ten-thousand Talents Program of Zhejiang Province/ ; QJD1802023//Qianjiang Talent Project of Zhejiang Province/ ; SQ2018YFE010015//National Key Research and Development Program/ ; }, mesh = {Acetates/pharmacology ; Animals ; Bacteria/genetics ; Brain ; *Cognitive Dysfunction ; *Diabetes Mellitus, Experimental ; *Gastrointestinal Microbiome ; Mice ; }, abstract = {BACKGROUND: Modification of the gut microbiota has been reported to reduce the incidence of type 1 diabetes mellitus (T1D). We hypothesized that the gut microbiota shifts might also have an effect on cognitive functions in T1D. Herein we used a non-absorbable antibiotic vancomycin to modify the gut microbiota in streptozotocin (STZ)-induced T1D mice and studied the impact of microbial changes on cognitive performances in T1D mice and its potential gut-brain neural mechanism.<br><br>RESULTS: We found that vancomycin exposure disrupted the gut microbiome, altered host metabolic phenotypes, and facilitated cognitive impairment in T1D mice. Long-term acetate deficiency due to depletion of acetate-producing bacteria resulted in the reduction of synaptophysin (SYP) in the hippocampus as well as learning and memory impairments. Exogenous acetate supplement or fecal microbiota transplant recovered hippocampal SYP level in vancomycin-treated T1D mice, and this effect was attenuated by vagal inhibition or vagotomy.<br><br>CONCLUSIONS: Our results demonstrate the protective role of microbiota metabolite acetate in cognitive functions and suggest long-term acetate deficiency as a risk factor of cognitive decline. Video Abstract.}, }
@article {pmid34171951, year = {2021}, author = {Špeciánová, Š}, title = {Legal aspects of intestinal microbiome application.}, journal = {Vnitrni lekarstvi}, volume = {67}, number = {E-3}, pages = {41-46}, pmid = {34171951}, issn = {0042-773X}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {Application of intestinal microbiome (Fecal Microbiota Transplantation) is currently discussed treatment procedure which is the subject of professional interest not only when it comes to its medical aspects, but also its legal regulation. The aim of this article is to introduce a legal perspective on this subject matter and outline possible newly regulated areas. The subject matter is linked not only with the legislation contained in the Czech Civil Code in the section devoted to products having its origin in the human body, but also with other laws in the area of medical law. The position of regulatory authorities in the EU is also mentioned. It is apparent that EUs regulatory authorities leave this area for the legislation of individual EU member States.}, }
@article {pmid34170204, year = {2021}, author = {Dharmaratne, P and Rahman, N and Leung, A and Ip, M}, title = {Is there a role of faecal microbiota transplantation in reducing antibiotic resistance burden in gut? A systematic review and Meta-analysis.}, journal = {Annals of medicine}, volume = {53}, number = {1}, pages = {662-681}, pmid = {34170204}, issn = {1365-2060}, abstract = {OBJECTIVES: The aim of current systematic review and meta-analysis is to provide insight into the therapeutic efficacy of fecal microbiota transplantation (FMT) for the decolonization of antimicrobial-resistant (AMR) bacteria from the gut.<br><br>METHODS: The protocol for this Systematic Review was prospectively registered with PROSPERO (CRD42020203634). Four databases (EMBASE, MEDLINE, SCOPUS, and WEB of SCIENCE) were consulted up until September 2020. A total of fourteen studies [in vivo (n = 2), case reports (n = 7), case series without control arm (n = 3), randomized clinical trials (RCT, n = 2)], were reviewed. Data were synthesized narratively for the case reports, along with a proportion meta-analysis for the case series studies (n = 102 subjects) without a control arm followed by another meta-analysis for case series studies with a defined control arm (n = 111 subjects) for their primary outcomes.<br><br>RESULTS: Overall, seven non-duplicate case reports (n = 9 participants) were narratively reviewed and found to have broad AMR remission events at the 1-month time point. Proportion meta-analysis of case series studies showed an overall 0.58 (95% CI: 0.42-0.74) AMR remission. Additionally, a significant difference in AMR remission was observed in FMT vs treatment naïve (RR = 0.44; 95% CI: 0.20-0.99) and moderate heterogeneity (I2=65%). A subgroup analysis of RCTs (n = 2) revealed FMT with further benefits of AMR remission with low statistical heterogeneity (RR = 0.37; 95% CI: 0.18-0.79; I2 =23%).<br><br>CONCLUSION: More rigorous RCTs with larger sample size and standardized protocols on FMTs for gut decolonization of AMR organisms are warranted.KEY MESSAGEExisting studies in this subject are limited and of low quality with moderate heterogeneity, and do not allow definitive conclusions to be drawn.More rigorous RCTs with larger sample size and standardized protocols on FMTs for gut decolonization of AMR organisms are warranted.}, }
@article {pmid34169565, year = {2021}, author = {Fehily, SR and Basnayake, C and Wright, EK and Kamm, MA}, title = {Fecal microbiota transplantation therapy in Crohn's disease: Systematic review.}, journal = {Journal of gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgh.15598}, pmid = {34169565}, issn = {1440-1746}, abstract = {BACKGROUND: The gastrointestinal microbiota is the key antigenic drive in the inflammatory bowel diseases. Randomized controlled trials (RCTs) in ulcerative colitis have established fecal microbiota transplantation (FMT) as an effective therapy. We have conducted a systematic review to evaluate the efficacy of FMT in Crohn's disease.<br><br>METHODS: A systematic literature search was performed through to August 2020 (MEDLINE; Embase). Studies were included if they reported FMT administration in patients with Crohn's disease, and reported on clinical outcomes.<br><br>RESULTS: Fifteen studies published between 2014 and 2020, comprising 13 cohort studies and two RCTs, were included in the analysis. The majority of trials evaluated FMT for induction of remission, with follow-up duration varying from 4 to 52 weeks. One RCT in 21 patients, of single-dose FMT versus placebo, following steroid-induced remission, showed a higher rate of steroid-free clinical remission in the FMT group compared to the control group: 87.5% vs 44.4% at week 10 (P = 0.23). Another RCT, two-dose FMT in 31 patients, showed an overall clinical remission rate of 36% at week 8, however, with no difference in clinical or endoscopic endpoints between FMT administered by gastroscopy and colonoscopy. Considering all studies, the clinical response rates in early follow up were higher following multiple FMT than with single FMT. FMT dose did not appear to influence clinical outcomes, nor did whether FMT was fresh or frozen. FMT delivered via upper gastrointestinal route demonstrated higher early efficacy rates of 75 to 100% compared with lower delivery route rates of 30% to 58%, but on follow up beyond 8 weeks, this difference was not maintained. Whether pre-FMT antibiotic administration was beneficial was not able to be determined due to the limited number of patients receiving antibiotics and varying antibiotic regimens. No serious adverse events were reported.<br><br>CONCLUSIONS: Preliminary studies suggest that FMT may be an effective therapy in Crohn's disease. However large controlled trials are needed. No serious safety concerns have been identified.}, }
@article {pmid34168535, year = {2021}, author = {Xu, X and Wang, K and Cao, X and Li, Z and Zhou, Y and Ren, J and Liu, F}, title = {Gut Microbial Metabolite Short-Chain Fatt Acids Partially Reverse Surgery and Anesthesia-Induced Behavior Deficits in C57BL/6J Mice.}, journal = {Frontiers in neuroscience}, volume = {15}, number = {}, pages = {664641}, pmid = {34168535}, issn = {1662-4548}, abstract = {Accumulating evidence has demonstrated that damages of gut microbiota are strongly associated with central nervous system (CNS) diseases, such as perioperative neurocognitive disorders (PND). The present study investigated the role of gut microbial metabolite short-chain fatty acids (SCFAs) in surgery-induced cognitive deficits and neuroinflammation in the hippocampus. Adult male C57BL/6J mice received either SCFA mixture or saline orally for 4 weeks, and then partial hepatectomy was performed. The fecal supernatant of surgical mice was transplanted to normal mice for 3 weeks. The Morris water maze (MWM) and open-field tests were used to evaluate behavioral performance on postoperative or post-transplantation days 3 and 7. In the MWM test, pretreatment with exogenous SCFAs partially reversed surgery-induced impairments in crossing times and the time spent in the target quadrant on postoperative day 3 (p < 0.05, p < 0.05, respectively). In the open-field test, compared with the surgical mice, exogenous SCFA administration prior to surgery partially improved the locomotor activity (p < 0.05) and anxiety-like behavior (p < 0.05) on postoperative day 3. Surgical trauma and anesthesia enhanced ionized calcium-binding adapter molecule 1 (Iba-1) expression (p < 0.001), increased the levels of interleukin (IL)-1β (p < 0.001) and IL-6 (p < 0.001), and inhibited SCFA production (p < 0.001) on postoperative day 3. The expression of the brain-derived neurotrophic factor (BDNF) was also decreased (p < 0.001). Overall, surgical trauma and anesthesia exacerbated cognitive impairment, enhanced neuroinflammatory responses, and inhibited SCFA production. Pretreatment with SCFAs attenuated these effects partially by reversing microglial overactivation, inhibiting neuroinflammatory responses, and enhancing BDNF expression.}, }
@article {pmid34168399, year = {2021}, author = {El-Salhy, M and Patcharatrakul, T and Gonlachanvit, S}, title = {Fecal microbiota transplantation for irritable bowel syndrome: An intervention for the 21st century.}, journal = {World journal of gastroenterology}, volume = {27}, number = {22}, pages = {2921-2943}, pmid = {34168399}, issn = {2219-2840}, mesh = {Diarrhea ; Fatty Acids, Volatile ; Fecal Microbiota Transplantation/adverse effects ; Feces ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome/therapy ; }, abstract = {Irritable bowel syndrome (IBS) affects about 12% of the global population. Although IBS does not develop into a serious disease or increase mortality, it results in a considerable reduction in the quality of life. The etiology of IBS is not known, but the intestinal microbiota appears to play a pivotal role in its pathophysiology. There is no effective treatment for IBS, and so the applied treatments clinically focus on symptom relief. Fecal microbiota transplantation (FMT), an old Chinese treatment, has been applied to IBS patients in seven randomized controlled trials (RCTs). Positive effects on IBS symptoms in various degrees were obtained in four of these RCTs, while there was no effect in the remaining three. Across the seven RCTs there were marked differences in the selection processes for the donor and treated patients, the transplant dose, the route of administration, and the methods used to measure how the patients responded to FMT. The present frontier discusses these differences and proposes: (1) criteria for selecting an effective donor (superdonor); (2) selection criteria for patients that are suitable for FMT; (3) the optimal FMT dose; and (4) the route of transplant administration. FMT appears to be safe, with only mild, self-limiting side effects of abdominal pain, cramping, tenderness, diarrhea, and constipation. Although it is early to speculate about the mechanisms underlying the effects of FMT, the available data suggest that changes in the intestinal bacteria accompanied by changes in fermentation patterns and fermentation products (specifically short-chain fatty acids) play an important role in improving the IBS symptoms seen after FMT. FMT appears to be a promising treatment for IBS, but further studies are needed before it can be applied in everyday clinical practice.}, }
@article {pmid34168032, year = {2021}, author = {Hoffmann-Vold, AM and Fretheim, HH and Sarna, VK and Barua, I and Carstens, MN and Distler, O and Khanna, D and Volkmann, ER and Midtvedt, Ø and Didriksen, H and Dhainaut, A and Halse, AK and Bakland, G and Pesonen, M and Olsen, I and Molberg, Ø}, title = {Safety and efficacy of faecal microbiota transplantation by Anaerobic Cultivated Human Intestinal Microbiome (ACHIM) in patients with systemic sclerosis: study protocol for the randomised controlled phase II ReSScue trial.}, journal = {BMJ open}, volume = {11}, number = {6}, pages = {e048541}, pmid = {34168032}, issn = {2044-6055}, mesh = {Anaerobiosis ; Clinical Trials, Phase II as Topic ; Double-Blind Method ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Los Angeles ; Multicenter Studies as Topic ; Pilot Projects ; Randomized Controlled Trials as Topic ; *Scleroderma, Systemic/therapy ; Treatment Outcome ; }, abstract = {INTRODUCTION: In the multisystem inflammatory disorder systemic sclerosis (SSc), gastrointestinal tract (GIT) affliction is highly prevalent. There are no known disease modifying therapies and the negative impact is substantial. Aiming for a new therapeutic principle, and inspired by recent work showing associations between gut microbiota changes and GIT symptoms in SSc, we performed a pilot study on faecal microbiota transplantation (FMT) with the single-donor bacterial culture 'Anaerobic Cultivated Human Intestinal Microbiome (ACHIM)'. Motivated by positive pilot study signals, we designed the ReSScue trial as a phase II multicentre, placebo-controlled, randomised 20-week trial to evaluate safety and efficacy on lower GIT symptoms of FMT by ACHIM in SSc.<br><br>METHODS AND ANALYSES: We aim to include 70 SSc participants with moderate to severe lower GIT symptoms, defined by the validated patient-reported University of California Los Angeles Scleroderma Clinical Trial Consortium GIT 2.0 2.0 questionnaire. The trial includes three parts. In part A1 (induction phase) lasting from week 0 to week 12, participants will be randomised 1:1 to repeat infusions of 30 mL ACHIM or placebo at week 0 and 2 by gastroduodenoscopy. In part A2, which is an 8-week subsequent maintenance phase, all study participants will receive 30 mL ACHIM at week 12 and followed until week 20 on continued blind. In part B, which will last until the last participant completes part A2, the participants will be followed through a maximum 16-week extended monitoring period, for longer-term data on safety and intervention effects. Primary endpoint is change from baseline to week 12 in UCLA GIT subscale scores of diarrhoea or bloating, depending on the worst symptom at baseline evaluated separately for each patient. Secondary endpoints are safety measures and changes in UCLA GIT scores (total, diarrhoea and bloating).<br><br>ETHICS AND DISSEMINATION: This protocol was approved by the Northern Norwegian Committee for Medical Ethics. Study findings will be published.<br><br>TRIAL REGISTRATION NUMBER: NCT04300426; Pre-results.<br><br>PROTOCOL VERSION: V.3.1.}, }
@article {pmid34163114, year = {2021}, author = {Nishida, A and Nishino, K and Sakai, K and Owaki, Y and Noda, Y and Imaeda, H}, title = {Can control of gut microbiota be a future therapeutic option for inflammatory bowel disease?.}, journal = {World journal of gastroenterology}, volume = {27}, number = {23}, pages = {3317-3326}, pmid = {34163114}, issn = {2219-2840}, mesh = {Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Inflammatory Bowel Diseases/therapy ; *Microbiota ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract encompassing two main clinical entities, Crohn's disease and ulcerative colitis. Accumulated evidence indicates that an aberrant immune activation caused by the interplay of genetic susceptibility and environmental impact on the gut microbiota may be involved in the pathogenesis of IBD. Rapid advances in next-generation sequencing technology have enabled a number of studies to identify the alteration of the gut microbiota, termed dysbiosis, in IBD. Moreover, the alteration in the metabolites derived from the gut microbiota in IBD has also been described in many studies. Therefore, microbiota-based interventions such as fecal microbiota transplantation (FMT) have attracted attention as a novel therapeutic option in IBD. However, in clinical trials, the efficacy of FMT for IBD remains controversial. Additional basic and clinical studies are required to validate whether FMT can assume a complementary role in the treatment of IBD. The present review provides a synopsis on dysbiosis in IBD and on the association between the gut microbiota and the pathogenesis of IBD. In addition, we summarize the use of probiotics in IBD and the results of current clinical trials of FMT for IBD.}, }
@article {pmid34162429, year = {2021}, author = {Hayase, E and Jenq, RR}, title = {Role of the intestinal microbiome and microbial-derived metabolites in immune checkpoint blockade immunotherapy of cancer.}, journal = {Genome medicine}, volume = {13}, number = {1}, pages = {107}, pmid = {34162429}, issn = {1756-994X}, support = {RR160089//Cancer Prevention and Research Institute of Texas (US)/ ; R01HL124112 and P30CA016672//Foundation for the National Institutes of Health/ ; }, abstract = {Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that block immune inhibitory pathways. Administration of ICIs augments T cell-mediated immune responses against tumor, resulting in improved overall survival in cancer patients. It has emerged that the intestinal microbiome can modulate responses to ICIs via the host immune system and that the use of antibiotics can lead to reduced efficacy of ICIs. Recently, reports that fecal microbiota transplantation can lead to ICI therapy responses in patients previously refractory to therapy suggest that targeting the microbiome may be a viable strategy to reprogram the tumor microenvironment and augment ICI therapy. Intestinal microbial metabolites may also be linked to response rates to ICIs. In addition to response rates, certain toxicities that can arise during ICI therapy have also been found to be associated with the intestinal microbiome, including in particular colitis. A key mechanistic question is how certain microbes can enhance anti-tumor responses or, alternatively, predispose to ICI-associated colitis. Evidence has emerged that the intestinal microbiome can modulate outcomes to ICI therapies via two major mechanisms, including those that are antigen-specific and those that are antigen-independent. Antigen-specific mechanisms occur when epitopes are shared between microbial and tumor antigens that could enhance, or, alternatively, reduce anti-tumor immune responses via cross-reactive adaptive immune cells. Antigen-independent mechanisms include modulation of responses to ICIs by engaging innate and/or adaptive immune cells. To establish microbiome-based biomarkers of outcomes and specifically modulate the intestinal microbiome to enhance efficacy of ICIs in cancer immunotherapy, further prospective interventional studies will be required.}, }
@article {pmid34158061, year = {2021}, author = {Patrono, E and Svoboda, J and Stuchlík, A}, title = {Schizophrenia, the gut microbiota, and new opportunities from optogenetic manipulations of the gut-brain axis.}, journal = {Behavioral and brain functions : BBF}, volume = {17}, number = {1}, pages = {7}, pmid = {34158061}, issn = {1744-9081}, support = {CZ.02.2.69/0.0/0.0/19_074/0016409//European Science Foundation/ ; 20-00939S//Grantová Agentura České Republiky/ ; 21-16667K//Grantová Agentura České Republiky/ ; }, abstract = {Schizophrenia research arose in the twentieth century and is currently rapidly developing, focusing on many parallel research pathways and evaluating various concepts of disease etiology. Today, we have relatively good knowledge about the generation of positive and negative symptoms in patients with schizophrenia. However, the neural basis and pathophysiology of schizophrenia, especially cognitive symptoms, are still poorly understood. Finding new methods to uncover the physiological basis of the mental inabilities related to schizophrenia is an urgent task for modern neuroscience because of the lack of specific therapies for cognitive deficits in the disease. Researchers have begun investigating functional crosstalk between NMDARs and GABAergic neurons associated with schizophrenia at different resolutions. In another direction, the gut microbiota is getting increasing interest from neuroscientists. Recent findings have highlighted the role of a gut-brain axis, with the gut microbiota playing a crucial role in several psychopathologies, including schizophrenia and autism.There have also been investigations into potential therapies aimed at normalizing altered microbiota signaling to the enteric nervous system (ENS) and the central nervous system (CNS). Probiotics diets and fecal microbiota transplantation (FMT) are currently the most common therapies. Interestingly, in rodent models of binge feeding, optogenetic applications have been shown to affect gut colony sensitivity, thus increasing colonic transit. Here, we review recent findings on the gut microbiota-schizophrenia relationship using in vivo optogenetics. Moreover, we evaluate if manipulating actors in either the brain or the gut might improve potential treatment research. Such research and techniques will increase our knowledge of how the gut microbiota can manipulate GABA production, and therefore accompany changes in CNS GABAergic activity.}, }
@article {pmid34154439, year = {2021}, author = {Drekonja, DM and Shaukat, A and Zhang, JH and Reinink, AR and Nugent, S and Dominitz, JA and Davis-Karim, A and Gerding, DN and Kyriakides, TC}, title = {Microbiota or placebo after antimicrobial therapy for recurrent Clostridioides difficile at home: A clinical trial with novel home-based enrollment.}, journal = {Clinical trials (London, England)}, volume = {}, number = {}, pages = {17407745211021198}, doi = {10.1177/17407745211021198}, pmid = {34154439}, issn = {1740-7753}, abstract = {INTRODUCTION: Clostridiodes difficile infection is the leading cause of infectious diarrhea in the United States, with substantial morbidity and mortality. Recurrent infection is especially challenging, with each recurrence increasing the likelihood of a successive recurrence, leading to cycles of prolonged symptoms, frequent antimicrobial use, and decreased quality of life. Fecal microbiota transplantation to prevent recurrent infection is a promising intervention with a large effect size in observational studies, but with conflicting results from randomized controlled trials. We are conducting a Veterans Affairs-wide randomized controlled trial utilizing centralized case identification, with enrollment and fecal microbiota transplant administration occurring at the participant's home. This type of trial design significantly improves trial efficiency, greatly decreases trial cost, increases consistency of trial administration, and most importantly makes nationwide clinical trials in less-common diseases possible.<br><br>METHODS: This is a randomized comparison of capsule-delivered fecal microbiota transplant for the prevention of recurrent Clostridiodes difficile infection, administered after successful initial treatment of recurrent C. difficile infection with standard therapy. The primary endpoint is the incidence of recurrent C. difficile infection or death. Cases are identified by searching the Veterans Affairs Corporate Data Warehouse, with central study coordinators then reaching out to potential participants. Individuals meeting inclusion criteria and interested in participation are scheduled for in-home consent, randomization, and capsule administration, followed by telephone follow-up for 6 months. To mitigate risks of COVID-19, enrollment via video visits has been implemented.<br><br>RESULTS: A total of 102 participants have been enrolled through January 2021. Centralized case identification and in-home enrollment has facilitated enrollment from 34 unique states, with 38% being from rural or highly rural areas.<br><br>DISCUSSION: Centralized case identification and in-home enrollment is a feasible and innovative method of conducting randomized controlled trials in the Veterans Affairs system, improving access to clinical research for populations who may have difficulty engaging with the traditional model of clinical trials where enrollment is based at large hospitals in major metropolitan areas.}, }
@article {pmid34153321, year = {2021}, author = {Thomaz, AC and Iyer, V and Woodward, TJ and Hohmann, AG}, title = {Fecal microbiota transplantation and antibiotic treatment attenuate naloxone-precipitated opioid withdrawal in morphine-dependent mice.}, journal = {Experimental neurology}, volume = {343}, number = {}, pages = {113787}, doi = {10.1016/j.expneurol.2021.113787}, pmid = {34153321}, issn = {1090-2430}, support = {R01 DA041229/DA/NIDA NIH HHS/United States ; R01 DA047858/DA/NIDA NIH HHS/United States ; R21 DA042584/DA/NIDA NIH HHS/United States ; T32 DA024628/DA/NIDA NIH HHS/United States ; }, abstract = {Opioid addiction can produce severe side effects including physical dependence and withdrawal. Perturbations of the gut microbiome have recently been shown to alter opioid-induced side-effects such as addiction, tolerance and dependence. In the present study, we investigated the influence of the gut microbiome on opioid withdrawal by evaluating the effects of fecal microbiota transplantation (FMT), antibiotic and probiotic treatments, and pharmacological inhibition of gut permeability in a mouse model of opioid dependence. Repeated intraperitoneal (i.p.) morphine treatment produced physical dependence that was quantified by measuring somatic signs of withdrawal (i.e. number of jumps) precipitated using the opioid antagonist naloxone. Morphine-dependent mice that received FMT from morphine-treated donor mice exhibited fewer naloxone-precipitated jumps compared to morphine-dependent counterparts receiving FMT from saline-treated donor mice. Microbial contents in the mouse cecum were altered by morphine treatment but were not differentially impacted by FMT. A broad-spectrum antibiotic cocktail (ABX) regimen reduced the bacterial load and attenuated naloxone-precipitated morphine withdrawal in morphine-dependent mice, whereas commercially available probiotic strains did not reliably alter somatic signs of opioid withdrawal. ML-7, a pharmacological inhibitor of gut permeability, reduced the morphine-induced increase in gut permeability in vivo but did not reliably alter somatic signs of naloxone-precipitated opioid withdrawal. Our results suggest that the gut microbiome impacts the development of physical dependence induced by chronic morphine administration, and that therapeutic manipulations of the gut microbiome may reduce opioid withdrawal.}, }
@article {pmid34152776, year = {2021}, author = {Yan, X and Ren, X and Liu, X and Wang, Y and Ma, J and Song, R and Wang, X and Dong, Y and Fan, Q and Wei, J and Yu, A and She, G}, title = {Dietary Ursolic Acid Prevents Alcohol-Induced Liver Injury via Gut-Liver Axis Homeostasis Modulation: The Key Role of Microbiome Manipulation.}, journal = {Journal of agricultural and food chemistry}, volume = {69}, number = {25}, pages = {7074-7083}, doi = {10.1021/acs.jafc.1c02362}, pmid = {34152776}, issn = {1520-5118}, mesh = {Animals ; *Chemical and Drug Induced Liver Injury, Chronic ; *Gastrointestinal Microbiome ; Homeostasis ; Liver ; *Liver Diseases, Alcoholic/drug therapy/prevention &amp; control ; Mice ; *Triterpenes ; }, abstract = {Ursolic acid (UA), a natural triterpenoid widely distributed within fruits and edible plants, has been proven to relieve alcoholic liver disease (ALD). However, the mechanisms involved largely remain unclear. This study investigated whether the beneficial effects of UA on ALD could be related to gut-liver axis (GLA) modulation. Special attention was paid to the contribution of gut microbiome manipulation. UA ameliorated intestinal oxidative stress and barrier dysfunction induced by alcohol. As a consequence of gut leakiness amelioration, the related endotoxemia-mediated liver toll-like receptor 4 pathway induction and the subsequent reactive oxygen species overproduction were reverted. UA also counteracted alcohol-induced gut dysbiosis. A fecal microbiota transplantation study indicated that liver injury as well as ileum oxidative stress and gut barrier dysfunction of recipient mice were partly ameliorated as a result of microbiome remodeling. These results suggest that dietary UA alleviates ALD through GLA homeostasis modulation. Gut microbiome manipulation contributes to the hepatoprotective activity and GLA modulating effect of UA.}, }
@article {pmid34152347, year = {2021}, author = {Deng, L and Zeng, H and Hu, X and Xiao, M and He, D and Zhang, Y and Jin, Y and Hu, Y and Zhu, Y and Gong, L and Wang, Z and Xiang, L and Zhu, R and Zhang, Y and Cheng, Y and Chen, X and Zhang, S and Peng, Y and Cao, K}, title = {Se@Albumin nanoparticles ameliorate intestinal mucositis caused by cisplatin via gut microbiota-targeted regulation.}, journal = {Nanoscale}, volume = {13}, number = {25}, pages = {11250-11261}, doi = {10.1039/d0nr07981b}, pmid = {34152347}, issn = {2040-3372}, mesh = {Albumins ; Animals ; Cisplatin ; Fluorouracil ; *Gastrointestinal Microbiome ; Mice ; *Mucositis ; *Nanoparticles ; }, abstract = {Chemotherapy-associated intestinal mucositis is still one of the major challenges in the first-line clinical cancer treatment. Selenium element has shown health benefits on enteritis upon uptake in trace amounts; however, it was limited because of its narrow safety margin. In this work, a new form of Se@Albumin complex nanoparticles (Se@Albumin NPs) was developed by self-assembly of denatured human serum albumin and selenite salts. Se@Albumin NPs significantly improve intestinal mucositis induced with cisplatin (CDDP) in a mouse model via attenuating the level of intestinal oxidative stress, reducing intestinal permeability, and relieving gastric dysmotility. It is very interesting that the restoration of anti-inflammatory bacteria (Bacteroidetes and Firmicutes) and reduced abundance of proinflammatory bacteria (Escherichia) contributed to the reduction of intestinal mucositis by Se@Albumin NPs in mice. In addition, the fecal microbiota transplantation (FMT) with materials from Se@Albumin NP-treated mice significantly protected pseudo-aseptic mice from CDDP-induced intestinal mucositis. In conclusion, our findings showed that Se@Albumin NPs can significantly improve CDDP-induced intestinal mucositis, and its function may be directly mediated by gut microbiota regulation, which will provide new helpful information for clinical treatment.}, }
@article {pmid34151049, year = {2021}, author = {West, C and McVey Neufeld, KA}, title = {Animal models of visceral pain and the role of the microbiome.}, journal = {Neurobiology of pain (Cambridge, Mass.)}, volume = {10}, number = {}, pages = {100064}, pmid = {34151049}, issn = {2452-073X}, abstract = {Visceral pain refers to pain arising from the internal organs and is distinctly different from the expression and mechanisms of somatic pain. Diseases and disorders with increased visceral pain are associated with significantly reduced quality of life and incur large financial costs due to medical visits and lost work productivity. In spite of the notable burden of illness associated with those disorders involving increased visceral pain, and some knowledge regarding etiology, few successful therapeutics have emerged, and thus increased attention to animal models of visceral hypersensitivity is warranted in order to elucidate new treatment opportunities. Altered microbiota-gut-brain (MGB) axis communication is central to the comorbid gastrointestinal/psychiatric diseases of which increased visceral (intestinal) sensitivity is a hallmark. This has led to a particular focus on intestinal microbiome disruption and its potential role in the etiology of heightened visceral pain. Here we provide a review of studies examining models of heightened visceral pain due to altered bidirectional communication of the MGB axis, many of which are conducted on a background of stress exposure. We discuss work in which the intestinal microbiota has either been directly manipulated (as with germ-free, antibiotic, and fecal microbial transplantation studies) or indirectly affected through early life or adult stress, inflammation, and infection. Animal models of visceral pain alterations with accompanying changes to the intestinal microbiome have the highest face and construct validity to the human condition and are the focus of the current review.}, }
@article {pmid34150673, year = {2021}, author = {Varga, A and Kocsis, B and Sipos, D and Kása, P and Vigvári, S and Pál, S and Dembrovszky, F and Farkas, K and Péterfi, Z}, title = {How to Apply FMT More Effectively, Conveniently and Flexible - A Comparison of FMT Methods.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {657320}, pmid = {34150673}, issn = {2235-2988}, mesh = {*Clostridioides difficile ; *Clostridium Infections ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; Recurrence ; Treatment Outcome ; }, abstract = {Purpose: Metronidazol and vancomycin were long the two best options against Clostridioides (formerly Clostridium) difficile infections (CDI). Now, the cost of new drugs such as fidaxomicin directs us towards alternative treatment options, such as faecal microbiota transplant (FMT). Its effectiveness is similar to fidaxomicin. There are questions regarding its safety, but the biggest challenges are prejudice and inconvenience. Most protocols refer to FMT applied in the form of a solution. We investigated different modalities of FMT.<br><br>Methods: Instead of using nasoenteric tubes or colonoscopy, we place frozen or lyophilised stool in non-coated, size "00", hard gelatine capsules or enterosolvent, size "0" capsules.<br><br>Results: We found that non-coated, size "00", hard gelatine capsules are appropriate for conducting FMT. Capsules containing lyophilised supernatant with a low number of bacteria have been proven to be non-inferior to other FMT modalities. The primary cure rate in the supernatant group was 93.75%, and 66.67% in the sediment group. The overall cure rate was 82.14%. Depending on the protocol, 4-7 capsules are sufficient per patient. Capsules can be stored for up to one year at -20°C.<br><br>Conclusions: FMT is a feasible alternative to antibiotic treatments in CDI. Our method makes the process flexible and less inconvenient to patients. Long storage time allows a consistent supply of capsules, while small volume and formulation make the procedure tolerable.}, }
@article {pmid34149723, year = {2021}, author = {Ponce-Alonso, M and García-Hoz, C and Halperin, A and Nuño, J and Nicolás, P and Martínez-Pérez, A and Ocaña, J and García-Pérez, JC and Guerrero, A and López-Sanromán, A and Cantón, R and Roy, G and Del Campo, R}, title = {An Immunologic Compatibility Testing Was Not Useful for Donor Selection in Fecal Microbiota Transplantation for Ulcerative Colitis.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {683387}, pmid = {34149723}, issn = {1664-3224}, abstract = {Fecal microbiota transplantation (FMT) is an effective procedure against Clostridioides difficile infection (CDI), with promising but still suboptimal performance in other diseases, such as ulcerative colitis (UC). The recipient's mucosal immune response against the donor's microbiota could be relevant factor in the effectiveness of FMT. Our aim was to design and validate an individualized immune-based test to optimize the fecal donor selection for FMT. First, we performed an in vitro validation of the test by co-culturing lymphocytes obtained from the small intestine mucosa of organ donor cadavers (n=7) and microbe-associated molecular patterns (MAMPs) obtained from the feces of 19 healthy donors. The inflammatory response was determined by interleukin supernatant quantification using the Cytometric Bead Array kit (B&amp;D). We then conducted a clinical pilot study with 4 patients with UC using immunocompetent cells extracted from rectal biopsies and MAMPs from 3 donor candidates. We employed the test results to guide donor selection for FMT, which was performed by colonoscopy followed by 4 booster instillations by enema in the following month. The microbiome engraftment was assessed by 16S rDNA massive sequencing in feces, and the patients were clinically followed-up for 16 weeks. The results demonstrated that IL-6, IL-8, and IL-1ß were the most variable markers, although we observed a general tolerance to the microbial insults. Clinical and colonoscopy remission of the patients with UC was not achieved after 16 weeks, although FMT provoked enrichment of the Bacteroidota phylum and Prevotella genus, with a decrease in the Actinobacteriota phylum and Agathobacter genus. The most relevant result was the lack of Akkermansia engraftment in UC. In summary, the clinical success of FMT in patients with UC appears not to be influenced by donor selection based on the explored recipient's local immunological response to FMT, suggesting that this approach would not be valid for FMT fecal donor optimization in such patients.}, }
@article {pmid34147969, year = {2021}, author = {Wang, S and Ishima, T and Qu, Y and Shan, J and Chang, L and Wei, Y and Zhang, J and Pu, Y and Fujita, Y and Tan, Y and Wang, X and Ma, L and Wan, X and Hammock, BD and Hashimoto, K}, title = {Ingestion of Faecalibaculum rodentium causes depression-like phenotypes in resilient Ephx2 knock-out mice: A role of brain-gut-microbiota axis via the subdiaphragmatic vagus nerve.}, journal = {Journal of affective disorders}, volume = {292}, number = {}, pages = {565-573}, pmid = {34147969}, issn = {1573-2517}, support = {P42 ES004699/ES/NIEHS NIH HHS/United States ; R35 ES030443/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Brain ; *Depression/genetics ; Eating ; Epoxide Hydrolases ; Firmicutes ; *Gastrointestinal Microbiome/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Phenotype ; Stress, Psychological ; Vagus Nerve ; }, abstract = {BACKGROUND: The brain-gut-microbiota axis plays a crucial role in the bidirectional interactions between the brain and the gut. Soluble epoxide hydrolase (coded by the Ephx2 gene) plays an important role in inflammation, which has been implicated in stress-related depression. Ephx2 knock-out (KO) mice exposed to chronic social defeat stress (CSDS) did not show depression-like behaviors, indicating stress resilience. Here we examined whether the brain-gut-microbiota axis influences the resilience in Ephx2 KO mice.<br><br>METHODS: Effects of fecal microbiota transplantation (FMT) from CSDS-susceptible (or control) mice in wild-type (WT) mice and Ephx2 KO mice treated with an antibiotic cocktail (ABX) were investigated. Behavioral, biochemical tests and 16S ribosome RNA analysis were performed.<br><br>RESULTS: FMT from CSDS-susceptible mice produced anhedonia-like behavior in ABX-treated WT and Ephx2 KO mice. The 16S ribosome RNA analysis showed that Faecalibaculum rodentium (F. rodentium) may be responsible for the observed anhedonia-like behavior following FMT from CSDS-susceptible mice. Ingestion of F. rodentium for 14 days produced depression- and anhedonia-like behaviors, higher blood levels of interleukin-6, and reduced expression of synaptic proteins in the prefrontal cortex of ABX-treated Ephx2 KO mice. Furthermore, subdiaphragmatic vagotomy blocked the development of these behavioral abnormalities after ingestion of F. rodentium.<br><br>LIMITATIONS: Detailed mechanisms are unclear.<br><br>CONCLUSIONS: These findings suggest that F. rodentium might contribute to the conversion of resilient Ephx2 KO mice into KO mice with depression-like phenotypes. The brain-gut-microbiota axis via the subdiaphragmatic vagus nerve plays a crucial role in susceptibility and resilience to stress.}, }
@article {pmid34145677, year = {2021}, author = {El-Salhy, M and Kristoffersen, AB and Valeur, J and Casen, C and Hatlebakk, JG and Gilja, OH and Hausken, T}, title = {Long-term effects of fecal microbiota transplantation (FMT) in patients with irritable bowel syndrome.}, journal = {Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society}, volume = {}, number = {}, pages = {e14200}, doi = {10.1111/nmo.14200}, pmid = {34145677}, issn = {1365-2982}, support = {40415//Helse Fonna/ ; }, abstract = {BACKGROUND: We recently found fecal microbiota transplantation (FMT) in irritable bowel syndrome (IBS) patients to be an effective and safe treatment after 3 months. The present follow-up study investigated the efficacy and safety of FMT at 1 year after treatment.<br><br>METHODS: This study included 77 of the 91 IBS patients who had responded to FMT in our previous study. Patients provided a fecal sample and completed five questionnaires to assess their symptoms and quality of life at 1 year after FMT. The dysbiosis index (DI) and fecal bacterial profile were analyzed using a 16S rRNA gene-based DNA probe hybridization. The levels of fecal short-chain fatty acids (SCFAs) were determined by gas chromatography.<br><br>RESULTS: There was a persistent response to FMT at 1 year after treatment in 32 (86.5%) and 35 (87.5%) patients who received 30-g and 60-g FMT, respectively. In the 30-g FMT group, 12 (32.4%) and 8 (21.6%) patients showed complete remission at 1 year and 3 months, respectively; the corresponding numbers in the 60-g FMT group were 18 (45%) and 11 (27.5%), respectively. Abdominal symptoms and the quality of life were improved at 1 year compared with after 3 months. These findings were accompanied by comprehensive changes in the fecal bacterial profile and SCFAs.<br><br>CONCLUSIONS: Most of the IBS patients maintained a response at 1 year after FMT. Moreover, the improvements in symptoms and quality of life increased over time. Changes in DI, fecal bacterial profile and SCFAs were more comprehensive at 1 year than after 3 months. www.clinicaltrials.gov (NCT03822299).}, }
@article {pmid34144192, year = {2021}, author = {Tang, B and Zhu, J and Fang, S and Wang, Y and Vinothkumar, R and Li, M and Weng, Q and Zheng, L and Yang, Y and Qiu, R and Xu, M and Zhao, Z and Ji, J}, title = {Pharmacological inhibition of MELK restricts ferroptosis and the inflammatory response in colitis and colitis-propelled carcinogenesis.}, journal = {Free radical biology &amp; medicine}, volume = {172}, number = {}, pages = {312-329}, doi = {10.1016/j.freeradbiomed.2021.06.012}, pmid = {34144192}, issn = {1873-4596}, abstract = {INTRODUCTION: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a group of chronic recurrent and incurable gastrointestinal diseases with an unknown etiology that leads to a high risk of developing colitis-associated colorectal cancer (CRC).<br><br>OBJECTIVES: In this study, we measured the expression characteristics of MELK in IBD and CRC tissues and explored the regulatory effect of OTSSP167 (a MELK-selective inhibitor) on the mice models of colitis and colitis-associated carcinogenesis and analyzed the specific molecular mechanisms.<br><br>METHODS: DSS-induced colitis and colitis-associated carcinogenesis (CAC) model were treated with MELK inhibitor OTSSP167 then the fight against effect of OTSSP167 in the clinical symptoms of colitis and CAC was measured. In addition, underlying mechanism of OTSSP167 treatment in vitro and vivo including anti-ferroptosis and anti-inflammatory response effect was further explored.<br><br>RESULTS: We found that pharmacological inhibition of MELK was indicated to significantly alleviate the inflammatory response in mice with colitis, reduce intestinal damage, and effectively inhibit the occurrence and progression of colitis-propelled carcinogenesis, which was closely related to the regulation of gut microbial composition, and OTSSP167-mediated fecal microbiota transplantation effectively alleviated DSS-induced colitis. In addition, OTSSP167 treatment obviously inhibited ferroptosis in the intestinal tissue and suppressed macrophage infiltration and M1 polarization, which reduced the secretion of pro-inflammatory factors. Further exploration of the molecular mechanism revealed that OTSSP167 inhibited AKT/IKK/P65 and ERK/IKK/P65 signaling cascades both in vivo and in vitro, which may help alleviate intestinal inflammation and control the occurrence of cancer.<br><br>CONCLUSION: Our findings lay a theoretical foundation for the use of OTSSP167 as a treatment for IBD and its inhibition of the occurrence of colitis-associated carcinogenesis; additionally, MELK may be a potentially effective target molecule, thus providing more options for clinical treatment.}, }
@article {pmid34142885, year = {2021}, author = {Silva, CBP and Elias-Oliveira, J and McCarthy, CG and Wenceslau, CF and Carlos, D and Tostes, RC}, title = {Ethanol: striking the cardiovascular system by harming the gut microbiota.}, journal = {American journal of physiology. Heart and circulatory physiology}, volume = {321}, number = {2}, pages = {H275-H291}, doi = {10.1152/ajpheart.00225.2021}, pmid = {34142885}, issn = {1522-1539}, support = {2018/14815-0//The Sao Paulo Research Foundation (FAPESP)/ ; K99 HL151889/HL/NHLBI NIH HHS/United States ; R00GM118885//Foundation for the National Institutes of Health (FNIH)/ ; R01HL149762//Foundation for the National Institutes of Health (FNIH)/ ; 2013/08216-2//The Sao Paulo Research Foundation/ ; K99HL151889//Foundation for the National Institutes of Health (FNIH)/ ; }, abstract = {Ethanol consumption represents a significant public health problem, and excessive ethanol intake is a risk factor for cardiovascular disease (CVD), one of the leading causes of death and disability worldwide. The mechanisms underlying the effects of ethanol on the cardiovascular system are complex and not fully comprehended. The gut microbiota and their metabolites are indispensable symbionts essential for health and homeostasis and therefore, have emerged as potential contributors to ethanol-induced cardiovascular system dysfunction. By mechanisms that are not completely understood, the gut microbiota modulates the immune system and activates several signaling pathways that stimulate inflammatory responses, which in turn, contribute to the development and progression of CVD. This review summarizes preclinical and clinical evidence on the effects of ethanol in the gut microbiota and discusses the mechanisms by which ethanol-induced gut dysbiosis leads to the activation of the immune system and cardiovascular dysfunction. The cross talk between ethanol consumption and the gut microbiota and its implications are detailed. In summary, an imbalance in the symbiotic relationship between the host and the commensal microbiota in a holobiont, as seen with ethanol consumption, may contribute to CVD. Therefore, manipulating the gut microbiota, by using antibiotics, probiotics, prebiotics, and fecal microbiota transplantation might prove a valuable opportunity to prevent/mitigate the deleterious effects of ethanol and improve cardiovascular health and risk prevention.}, }
@article {pmid34140459, year = {2021}, author = {Nicholson, MR and Hourigan, SK and Conrad, M and Goyal, A and Jensen, K and Kelsen, J and Kennedy, M and Weatherly, M and Kahn, SA}, title = {Current Challenges in Fecal Microbiota Transplantation for Clostridioides difficile Infection in Children.}, journal = {The American journal of gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.14309/ajg.0000000000001350}, pmid = {34140459}, issn = {1572-0241}, support = {K23 DK119585/DK/NIDDK NIH HHS/United States ; }, abstract = {INTRODUCTION: The impact of the 2019 US Food and Drug Administration safety alert involving transmission of multidrug resistant organisms through fecal microbiota transplantation (FMT), and the COVID-19 pandemic on the use of FMT in children, is unknown.<br><br>METHODS: A survey of pediatric gastroenterologists performing FMT for Clostridioides difficile infection was conducted.<br><br>RESULTS: Of 36 respondents, 17 (47%) and 30 (83%) changed their FMT practices related to the US Food and Drug Administration safety alert and COVID-19 pandemic, respectively, with 22 (61%) of programs halted.<br><br>DISCUSSION: The US Food and Drug Administration safety alert and COVID-19 pandemic have substantially influenced the availability and access of FMT for children.}, }
@article {pmid34139232, year = {2021}, author = {Chatterjee, S and Bose, D and Seth, R}, title = {Host gut microbiome and potential therapeutics in Gulf War Illness: A short review.}, journal = {Life sciences}, volume = {280}, number = {}, pages = {119717}, doi = {10.1016/j.lfs.2021.119717}, pmid = {34139232}, issn = {1879-0631}, mesh = {Animals ; Dysbiosis/microbiology/therapy/virology ; Fatty Acids, Volatile/therapeutic use ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Persian Gulf Syndrome/microbiology/*therapy/virology ; Phenols/therapeutic use ; Probiotics/therapeutic use ; }, abstract = {AIMS: Since our troops had returned from the first Persian Gulf War in 1990-91, the veterans have reported chronic multisymptomatic illness widely referred to as Gulf War Illness (GWI). We aim to review the current directions of GWI pathology research in the context of chronic multisymptomatic illness and its possible gut microbiome targeted therapies. The veterans of Gulf War show symptoms of chronic fatigue, cognitive deficits, and a subsection report of gastrointestinal complications.<br><br>METHOD: Efforts of finding a suitable treatment regimen and clinical management remain a challenge. More recently, we have shown that the pathology is connected to alterations in the gut microbiome, and efforts of finding a suitable regimen for gut-directed therapeutics are underway. We discuss the various clinical interventions and summarize the possible effectiveness of gut-directed therapies such as the use of short-chain fatty acids (SCFA), phenolic compounds, and their metabolites, use of probiotics, and fecal microbiota transfer.<br><br>SIGNIFICANCE: The short review will be helpful to GWI researchers to expand their studies to the gut and find an effective treatment strategy for chronic multisymptomatic illness.}, }
@article {pmid34139173, year = {2021}, author = {Zhu, W and Romano, KA and Li, L and Buffa, JA and Sangwan, N and Prakash, P and Tittle, AN and Li, XS and Fu, X and Androjna, C and DiDonato, AJ and Brinson, K and Trapp, BD and Fischbach, MA and Rey, FE and Hajjar, AM and DiDonato, JA and Hazen, SL}, title = {Gut microbes impact stroke severity via the trimethylamine N-oxide pathway.}, journal = {Cell host &amp; microbe}, volume = {29}, number = {7}, pages = {1199-1208.e5}, pmid = {34139173}, issn = {1934-6069}, support = {P01 HL147823/HL/NHLBI NIH HHS/United States ; R01 HL103866/HL/NHLBI NIH HHS/United States ; R01 HL150537/HL/NHLBI NIH HHS/United States ; T32 HL134622/HL/NHLBI NIH HHS/United States ; }, abstract = {Clinical studies have demonstrated associations between circulating levels of the gut-microbiota-derived metabolite trimethylamine-N-oxide (TMAO) and stroke incident risk. However, a causal role of gut microbes in stroke has not yet been demonstrated. Herein we show that gut microbes, through dietary choline and TMAO generation, directly impact cerebral infarct size and adverse outcomes following stroke. Fecal microbial transplantation from low- versus high-TMAO-producing human subjects into germ-free mice shows that both TMAO generation and stroke severity are transmissible traits. Furthermore, employing multiple murine stroke models and transplantation of defined microbial communities with genetically engineered human commensals into germ-free mice, we demonstrate that the microbial cutC gene (an enzymatic source of choline-to-TMA transformation) is sufficient to transmit TMA/TMAO production, heighten cerebral infarct size, and lead to functional impairment. We thus reveal that gut microbiota in general, specifically the metaorganismal TMAO pathway, directly contributes to stroke severity.}, }
@article {pmid34137411, year = {2021}, author = {Zhao, R and Ji, Y and Chen, X and Hu, Q and Zhao, L}, title = {Polysaccharide from Flammulina velutipes attenuates markers of metabolic syndrome by modulating the gut microbiota and lipid metabolism in high fat diet-fed mice.}, journal = {Food &amp; function}, volume = {12}, number = {15}, pages = {6964-6980}, doi = {10.1039/d1fo00534k}, pmid = {34137411}, issn = {2042-650X}, abstract = {Natural biological macromolecules with putative functions of gut microbiota regulation possess the advantage of improving metabolic syndrome (MS). In this research, we aimed to determine the effects of Flammulina velutipes polysaccharide (FVP) (Expt. 1) and fecal microbiota transplantation (FMT) (Expt. 2) on MS-related disorders, gut microbiota structure changes and their underlying mechanisms in a murine model fed with high-fat diet (HFD). In Expt. 1, six-week-old male C57BL/6J mice were fed with a control diet (10% calories from fat) or a high fat diet (45% calories from fat), administered with saline or FVP (0.4 mg per g b.w.) by gavage over a 12-week period. In Expt. 2, mice were fed with a HFD, administered with fecal supernatants from healthy and FVP-fed donor mice for 12 weeks simultaneously. The body mass, blood lipid levels and blood glucose homeostasis of mice were analyzed, and total RNA from mouse liver and adipose tissue were extracted by TRIzol and the lipid metabolism-related gene expressions were calculated by qRT-PCR. Gut microbiota changes were evaluated by high-throughput sequencing. Results indicated that FVP and FMT supplementations showed an attenuation effect on mouse obesity, hyperlipidemia and insulin resistance. Up-regulated expressions of Ampkα1 and Ppara were found both in FVP and FMT treatment groups. Different changes were found in the gut microbiota caused by FVP and FMT, respectively. PICRUSt analysis indicated that compared with FVP supplementation, FMT showed a significant effect on regulating lipid metabolism in HFD-fed mice. The findings from this study indicated that oral administrations of FVP or FMT could significantly attenuate MS-related obesity, hyperlipidemia and insulin resistance in HFD-fed mice, and the beneficial effects may be mediated through lipid metabolism and gut microbiota regulation in different ways. These results improve the understanding of the functional activity of FVP as prebiotics.}, }
@article {pmid34135557, year = {2021}, author = {Wen, X and Wang, HG and Zhang, MN and Zhang, MH and Wang, H and Yang, XZ}, title = {Fecal microbiota transplantation ameliorates experimental colitis via gut microbiota and T-cell modulation.}, journal = {World journal of gastroenterology}, volume = {27}, number = {21}, pages = {2834-2849}, pmid = {34135557}, issn = {2219-2840}, mesh = {Animals ; CD8-Positive T-Lymphocytes ; *Colitis/chemically induced/therapy ; *Colitis, Ulcerative/chemically induced/therapy ; Colon ; Dextran Sulfate/toxicity ; Disease Models, Animal ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Mice ; }, abstract = {BACKGROUND: Emerging evidence has demonstrated that fecal microbiota transplantation (FMT) has a promising therapeutic effect on mice with experimental colitis and patients with ulcerative colitis (UC), although the mechanism of FMT is unclear.<br><br>AIM: To evaluate the protective effect of FMT on UC and clarify its potential dependence on the gut microbiota, through association analysis of gut microbiota with colon transcriptome in mice.<br><br>METHODS: Dextran sodium sulfate (DSS)-induced experimental colitis was established and fecal microbiota was transplanted by gavage. Severity of colon inflammation was measured by body weight, disease activity index, colon length and histological score. Gut microbiota alteration was analyzed through 16S ribosomal ribonucleic acid sequencing. The differentially expressed genes (DEGs) in the colon were obtained by transcriptome sequencing. The activation status of colonic T lymphocytes in the lamina propria was evaluated by flow cytometry.<br><br>RESULTS: Compared with the DSS group, the weight loss, colon length shortening and inflammation were significantly alleviated in the FMT group. The scores of disease activity index and colon histology decreased obviously after FMT. FMT restored the balance of gut microbiota, especially by upregulating the relative abundance of Lactobacillus and downregulating the relative abundance of Clostridium_sensu_stricto_1 and Turicibacter. In the transcriptomic analysis, 128 DEGs intersected after DSS treatment and FMT. Functional annotation analysis suggested that these DEGs were mainly involved in T-lymphocyte activation. In the DSS group, there was an increase in colonic T helper CD4+ and T cytotoxic CD8+ cells by flow cytometry. FMT selectively downregulated the ratio of colonic CD4+ and CD8+ T cells to maintain intestinal homeostasis. Furthermore, Clostri dium_sensu_stricto_1 was significantly related to inflammation-related genes including REG3G, CCL8 and IDO1.<br><br>CONCLUSION: FMT ameliorated DSS-induced colitis in mice via regulating the gut microbiota and T-cell modulation.}, }
@article {pmid34134605, year = {2021}, author = {Zhao, J and Bai, M and Yang, X and Wang, Y and Li, R and Sun, S}, title = {Alleviation of refractory IgA nephropathy by intensive fecal microbiota transplantation: the first case reports.}, journal = {Renal failure}, volume = {43}, number = {1}, pages = {928-933}, doi = {10.1080/0886022X.2021.1936038}, pmid = {34134605}, issn = {1525-6049}, abstract = {BACKGROUND: Gut dysbiosis may be implicated in the pathogenesis of IgA nephropathy (IgAN) through immune and/or metabolite pathways. Fecal microbiota transplantation (FMT) could reestablish the micro-ecological balance in IgAN, although this has never been attempted before. We explored whether FMT could be efficacious in treating IgAN in two patients with refractory IgAN.<br><br>CASE PRESENTATION: Two Chinese female patients with IgAN failed to achieve clinical remission after receiving several rounds of immunosuppressive therapy and suffered from unbearable adverse effects due to immunosuppressants. Both patients received intensive fresh FMT conducted through transendoscopic enteral tubing (TET) regularly for 6-7 months, and were followed up for a further 6 months. Partial clinical remission was achieved in both patients, evidenced by a decrease in the 24-h urinary protein (24-hUP) to less than half of baseline during FMT treatment or follow-up, along with increased serum albumin (sAlb) and stable kidney function. The gut microbiota of both patients was distorted with lower biodiversity and altered composition, which was reversed following FMT. Phylum Proteobacteria decreased while genus Prevotella increased during and after FMT. The intensive fresh FMT was well-tolerated, and no severe adverse events occurred.<br><br>CONCLUSIONS: Preliminary evidence of the safety and efficacy of FMT for treating refractory IgAN may provide a new direction by which to decipher the pathogenesis of IgAN.}, }
@article {pmid34133889, year = {2021}, author = {Mehta, N and Wang, T and Friedman-Moraco, RJ and Carpentieri, C and Mehta, AK and Rouphael, N and Dhere, T and Larsen, CP and Kraft, CS and Woodworth, MH}, title = {Fecal Microbiota Transplantation Donor Screening Updates and Research Gaps for Solid Organ Transplant Recipients.}, journal = {Journal of clinical microbiology}, volume = {}, number = {}, pages = {JCM0016121}, doi = {10.1128/JCM.00161-21}, pmid = {34133889}, issn = {1098-660X}, abstract = {In this review, we discuss stool donor screening considerations to mitigate potential risks of pathogen transmission through fecal microbiota transplant (FMT) in solid organ transplant (SOT) recipients. SOT recipients have a higher risk for Clostridioides difficile infection (CDI) and are more likely to have severe CDI. FMT has been shown to be a valuable tool in the treatment of recurrent CDI (RCDI), however guidelines for screening for opportunistic infections transmitted through FMT are underdeveloped. We review reported adverse effects of FMT as they pertain to an immunocompromised population and discuss current understanding and recommendations for screening found in the literature while noting gaps in research. We conclude that while FMT is being performed in the SOT population, typically with positive results, there remain many unanswered questions which may have major safety implications and warrant further study.}, }
@article {pmid34133861, year = {2021}, author = {Bajaj, JS and Kamath, PS and Reddy, KR}, title = {The Evolving Challenge of Infections in Cirrhosis.}, journal = {The New England journal of medicine}, volume = {384}, number = {24}, pages = {2317-2330}, doi = {10.1056/NEJMra2021808}, pmid = {34133861}, issn = {1533-4406}, mesh = {Algorithms ; Anti-Bacterial Agents/therapeutic use ; Bacterial Infections/diagnosis/*etiology/therapy ; Candidiasis/etiology ; Chronic Disease ; Cross Infection/etiology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Hospital Mortality ; Humans ; Liver Cirrhosis/*complications/immunology/mortality ; Phage Therapy ; Risk Factors ; Sepsis/etiology ; }, }
@article {pmid34126062, year = {2021}, author = {Nooij, S and Ducarmon, QR and Laros, JFJ and Zwittink, RD and Norman, JM and Smits, WK and Verspaget, HW and Keller, JJ and Terveer, EM and Kuijper, EJ and , }, title = {Fecal Microbiota Transplantation Influences Procarcinogenic Escherichia coli in Recipient Recurrent Clostridioides difficile Patients.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2021.06.009}, pmid = {34126062}, issn = {1528-0012}, abstract = {BACKGROUND &amp; AIMS: Patients with multiple recurrent Clostridioides difficile infection (rCDI) have a disturbed gut microbiota that can be restored by fecal microbiota transplantation (FMT). Despite extensive screening, healthy feces donors may carry bacteria in their intestinal tract that could have long-term health effects, such as potentially procarcinogenic polyketide synthase-positive (pks+) Escherichia coli. Here, we aim to determine whether the pks abundance and persistence of pks+E coli is influenced by pks status of the donor feces.<br><br>METHODS: In a cohort of 49 patients with rCDI treated with FMT and matching donor samples-the largest cohort of its kind, to our knowledge-we retrospectively screened fecal metagenomes for pks+E coli and compared the presence of pks in patients before and after treatment and to their respective donors.<br><br>RESULTS: The pks island was more prevalent (P = .026) and abundant (P < .001) in patients with rCDI (pre-FMT, 27 of 49 [55%]; median, 0.46 reads per kilobase per million [RPKM] pks) than in healthy donors (3 of 8 donors [37.5%], 11 of 38 samples [29%]; median, 0.01 RPKM pks). The pks status of patients post-FMT depended on the pks status of the donor suspension with which the patient was treated (P = .046). Particularly, persistence (8 of 9 cases) or clearance (13 of 18) of pks+E coli in pks+ patients was correlated to pks in the donor (P = .004).<br><br>CONCLUSIONS: We conclude that FMT contributes to pks+E coli persistence or eradication in patients with rCDI but that donor-to-patient transmission of pks+E coli is unlikely.}, }
@article {pmid34120835, year = {2021}, author = {Biruete, A and Cross, TL and Allen, JM and Kistler, BM and de Loor, H and Evenepoel, P and Fahey, GC and Bauer, L and Swanson, KS and Wilund, KR}, title = {Effect of Dietary Inulin Supplementation on the Gut Microbiota Composition and Derived Metabolites of Individuals Undergoing Hemodialysis: A Pilot Study.}, journal = {Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.jrn.2020.10.003}, pmid = {34120835}, issn = {1532-8503}, abstract = {OBJECTIVE: The prebiotic fiber inulin has been studied in individuals undergoing hemodialysis (HD) due to its ability to reduce gut microbiota-derived uremic toxins. However, studies examining the effects of inulin on the gut microbiota and derived metabolites are limited in these patients. We aimed to assess the impact of a 4-week supplementation of inulin on the gut microbiota composition and microbial metabolites of patients on HD.<br><br>DESIGN AND METHODS: In a randomized, double-blind, placebo-controlled, crossover study, twelve HD patients (55 ± 10 y, 50% male, 58% Black American, BMI 31.6 ± 8.9 kg/m2, 33% diabetes mellitus) were randomized to consume inulin [10 g/d for females; 15 g/d for males] or maltodextrin [6 g/d for females; 9 g/d for males] for 4 weeks, with a 4-week washout period. We assessed the fecal microbiota composition, fecal metabolites (short-chain fatty acids (SCFA), phenols, and indoles), and plasma indoxyl sulfate and p-cresyl sulfate.<br><br>RESULTS: At baseline, factors that explained the gut microbiota variability included BMI category and type of phosphate binder prescribed. Inulin increased the relative abundance of the phylum Verrucomicrobia and its genus Akkermansia (P interaction = 0.045). Inulin and maltodextrin resulted in an increased relative abundance of the phylum Bacteroidetes and its genus Bacteroides (P time = 0.04 and 0.03, respectively). Both treatments increased the fecal acetate and propionate (P time = 0.032 and 0.027, respectively), and there was a trend toward increased fecal butyrate (P time = 0.06). Inulin did not reduce fecal p-cresol or indoles, or plasma concentrations of p-cresyl sulfate or indoxyl sulfate.<br><br>CONCLUSIONS: A 4-week supplementation of inulin did not lead to major shifts in the fecal microbiota and gut microbiota-derived metabolites. This may be due to high variability among participants and an unexpected increase in fecal excretion of SCFA with maltodextrin. Larger studies are needed to determine the effects of prebiotic fibers on the gut microbiota and clinical outcomes to justify their use in patients on HD.}, }
@article {pmid34118466, year = {2021}, author = {Yeh, YM and Cheng, HT and Le, PH and Chen, CC and Kuo, CJ and Chen, CL and Chiu, CT and Chiu, CH}, title = {Implementation of fecal microbiota transplantation in a medical center for recurrent or refractory Clostridioides difficile infection and report of preliminary outcome.}, journal = {Biomedical journal}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bj.2021.06.001}, pmid = {34118466}, issn = {2320-2890}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has been shown to highly effective in the treatment of recurrent or refractory Clostridioides difficile infection (rCDI) in many countries of the world. Not until 2018, Ministry of Health and Welfare, Taiwan approved the application of FMT for rCDI under a special law. The study reported the first implementation of the technology in the medical center in Taiwan and the preliminary outcome.<br><br>METHODS: FMT was used to treat patients with rCDI in Chang Gung Memorial Hospital. FMT was delivered by gastroenterologists using colonoscope. Strict donor screening was performed according to the guidelines. We followed up the clinical course of patients after FMT. 16S rRNA sequencing of fecal samples for donor, and also recipient before and after FMT was carried out.<br><br>RESULTS: From September 2018 to June 2020, 39 patients with rCDI received FMT, with a successful rate of 89.7%. Two patients died due to causes unrelated to FMT, and two other cases showed no clinical improvement after the procedure. High school and college students showed the best pass rate during donor screening. The presence of multi-drug resistant pathogen was the most common cause for screening failure. We demonstrated in a case the use of rRNA sequencing as a biomarker indicating for the improvement of dysbiosis in a patient after FMT.<br><br>CONCLUSIONS: FMT was successfully implemented in a medical center in Taiwan and showed a comparable successful rate in treating rCDI, compared to other countries. Safety remains the most important issue when applying FMT in the clinical setting.}, }
@article {pmid34118462, year = {2021}, author = {Li, Y and Cao, W and Gao, NL and Zhao, XM and Chen, WH}, title = {Consistent Alterations of Human Fecal Microbes after Transplantation into Germ-free Mice.}, journal = {Genomics, proteomics &amp; bioinformatics}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.gpb.2020.06.024}, pmid = {34118462}, issn = {2210-3244}, abstract = {Fecal microbiota transplantation (FMT) of human fecal samples into germ-free (GF) mice is useful for establishing causal relationships between the gut microbiota and human phenotypes. However, due to the intrinsic differences between human and mouse intestines and the different diets of the two organisms, it may not be possible to replicate human phenotypes in mice through FMT; similarly, treatments that are effective in mouse models may not be effective in humans. In this study, we aimed to identify human gut microbes that undergo significant and consistent changes (i.e., in relative abundances) after transplantation into GF mice in multiple experimental settings. We collected 16S rDNA-seq data from four published studies and analyzed the gut microbiota profiles from 1713 human-mouse pairs. Strikingly, on average, we found that only 47% of the human gut microbes could be re-established in mice at the species level, among which more than 1/3 underwent significant changes (referred to as "variable taxa"). Most of the human gut microbes that underwent significant changes were consistent across multiple human-mouse pairs and experimental settings. Consequently, about 1/3 of human samples changed their enterotypes, i.e., significant changes in their leading species after FMT. Mice fed with a controlled diet showed a lower enterotype change rate (23.5%) than those fed with a noncontrolled diet (49.0%), suggesting a possible solution for rescue. Most of the variable taxa have been reported to be implicated in human diseases, with some recognized as the causative species. Our results highlight the challenges of using a mouse model to replicate human gut microbiota-associated phenotypes, provide useful information for researchers using mice in gut microbiota studies, and call for additional validations after FMT. An online database named FMT-DB is publicly available at http://fmt2mice.humangut.info/#/.}, }
@article {pmid34118321, year = {2021}, author = {Núñez F, P and Quera, R and Bay, C and Thomson, P}, title = {Fecal microbiota transplant, its usefulness beyond Clostridioides difficile in gastrointestinal diseases.}, journal = {Gastroenterologia y hepatologia}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.gastrohep.2021.05.009}, pmid = {34118321}, issn = {0210-5705}, abstract = {Fecal microbiota transplant (FMT) is currently recommended for recurrent Clostridioidesdifficile infection. However, it is interesting to acknowledge the potential therapeutic role in other diseases associated with dysbiosis. This review will focus on the current and potential indications of FMT in gastrointestinal diseases, evaluating the available evidence and also exposing the necessary requirements to carry it out.}, }
@article {pmid34116562, year = {2021}, author = {Wu, Y and Chen, Y and Li, Q and Ye, X and Guo, X and Sun, L and Zou, J and Shen, Y and Mao, Y and Li, C and Yang, Y}, title = {Tetrahydrocurcumin alleviates allergic airway inflammation in asthmatic mice by modulating the gut microbiota.}, journal = {Food &amp; function}, volume = {12}, number = {15}, pages = {6830-6840}, doi = {10.1039/d1fo00194a}, pmid = {34116562}, issn = {2042-650X}, abstract = {Dietary factors can reshape the gut microbiota and consequently affect disease progression. We previously reported that tetrahydrocurcumin (THC), the major active metabolite of curcumin (Cur), could ameliorate allergic inflammation in asthmatic mice. Herein, we aimed to investigate whether THC or Cur exerts anti-inflammatory effects on allergic asthma via modulating gut microbiota. Ovalbumin (OVA)-induced asthmatic mice were treated with Cur or THC, and the gut microbiota profiles were analyzed by 16S rRNA sequencing. Fecal microbiota transplantation (FMT) from Cur- or THC-fed donor mice was administered to OVA-induced asthmatic mice. Nasal symptoms and inflammation patterns of lungs and colons were evaluated in control, OVA-induced and Cur-or THC-treated mice. Both Cur and THC treatment could alter the compositions of the gut microbiota in asthmatic mice, characterized by a significant decrease in the ratio of Firmicutes to Bacteroidetes; Cur or THC supplementation also reduced the relative abundances of pro-inflammatory bacteria, e.g., Proteobacteria, Intestinimonas, Unidentified-Ruminococcaceae, and Lachnospiraceae, in OVA-induced mice. The relative abundances of Unidentified-Ruminococcaceae, Romboutsia, Intestinimonas, Akkermansia, and Mucispirillum were positively associated with the levels of Th2-related factors in asthmatic mice upon Cur or THC treatment. Moreover, THC-FMT showed better preventive effects than Cur-FMT on the development of allergic inflammation in OVA-induced mice, resulting in a reduction in symptoms and Th2-mediated inflammation in both lung and colon tissues. The results reveal that Cur- or THC-mediated alleviation of airway allergic inflammation is dependent on gut microbiota modulation. THC-induced gut microbiota may have therapeutic potential for asthma treatment.}, }
@article {pmid34111616, year = {2021}, author = {Shao, S and Jia, R and Zhao, L and Zhang, Y and Guan, Y and Wen, H and Liu, J and Zhao, Y and Feng, Y and Zhang, Z and Ji, Q and Li, Q and Wang, Y}, title = {Xiao-Chai-Hu-Tang ameliorates tumor growth in cancer comorbid depressive symptoms via modulating gut microbiota-mediated TLR4/MyD88/NF-κB signaling pathway.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {88}, number = {}, pages = {153606}, doi = {10.1016/j.phymed.2021.153606}, pmid = {34111616}, issn = {1618-095X}, mesh = {Animals ; Antidepressive Agents/pharmacology ; Antineoplastic Agents/*pharmacology ; Colorectal Neoplasms/*drug therapy/metabolism/pathology ; Comorbidity ; Depression/drug therapy/epidemiology/*pathology ; Drugs, Chinese Herbal/*pharmacology ; Dysbiosis/drug therapy/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects/physiology ; Humans ; Male ; Mice, Inbred C57BL ; Middle Aged ; Myeloid Differentiation Factor 88/metabolism ; NF-kappa B/metabolism ; Toll-Like Receptor 4/metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {BACKGROUND: Depressive symptoms are thought to promote cancer development and depressive remission has been reported to be effective for defeating cancer. The herbal formula Xiao-Chai-Hu-Tang (XCHT), that has an anti-depressive efficacy, has been widely utilized in China. However, its anti-cancer effect and underlying mechanisms remain unclear.<br><br>PURPOSE: The present study aims to investigate the effects of XCHT on the depression-associated tumor and its potential mechanisms.<br><br>METHODS: A placebo-controlled trial was conducted in cancer patients comorbid with depressive symptoms to evaluate the effects of XCHT on depressive scales, tumor-related immune indicators, and gut microbial composition. A xenografted colorectal cancer (CRC) mouse model exposure to chronic restraint stress (CRS) was established to examine XCHT effects on tumorigenesis in vivo. Further, by manipulating gut bacteria with fecal microbial transplantation (FMT) or antibiotics-induced bacterial elimination in CRS-associated xenografted model, gut microbiota-mediated anti-tumor mechanism was explored.<br><br>RESULTS: In cancer patients comorbid with depressive symptoms, XCHT showed substantial effects on improvement of depressive scales, system inflammatory levels and gut dysbiosis. In vivo, XCHT inhibited tumor growth and prolonged survival time in addition to showing anti-depressive effect. Similarly, in our clinical trial, XCHT partially reversed gut dysbiosis, particularly through reducing abundances of Parabacteroides, Blautia and Ruminococcaceae bacterium. Manipulation of gut bacteria in CRS-associated xenografted model further proved that the inhibition of XCHT on tumor progression was mediated by gut microbiota and that the underlying mechanism involves in downregulation of TLR4/MyD88/NF-κB signaling.<br><br>CONCLUSIONS: We demonstrated that gut microbiota mediates the anti-tumor action of the formula XCHT in cancer patients and models that were comorbid with depressive symptoms. This study implies a novel clinical significance of anti-depressive herbal medicine in the cancer treatment and clarifies the important role of gut microbiota in treating cancer accompanied by depressive symptoms.}, }
@article {pmid34111528, year = {2021}, author = {Wang, M and Cao, J and Gong, C and Amakye, WK and Yao, M and Ren, J}, title = {Exploring the microbiota-Alzheimer's disease linkage using short-term antibiotic treatment followed by fecal microbiota transplantation.}, journal = {Brain, behavior, and immunity}, volume = {96}, number = {}, pages = {227-238}, doi = {10.1016/j.bbi.2021.06.003}, pmid = {34111528}, issn = {1090-2139}, mesh = {*Alzheimer Disease/therapy ; Amyloid beta-Peptides ; Animals ; Anti-Bacterial Agents ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Mice ; Mice, Transgenic ; *Microbiota ; }, abstract = {Gut microbiota is proven to be involved in the development of beta amyloid (Aβ) pathology in Alzheimer's disease (AD). Since there are difficulties in translating microbiota findings based on germ-free mice into clinical practice, here, we used short-term antibiotic cocktail treatment to develop a novel model with a near-germ-free status and without impacting Aβ pathology. Three months old APPSWE/PS1ΔE9 mice were fed with antibiotic cocktails for two weeks by gavage to obtain a near "germ-free" status, and then received the donor fecal matter from the 16 months old APPSWE/PS1ΔE9 mice for 7 consecutive days. Fecal pellets were collected prior to antibiotics treatment, following antibiotic exposure, prior to and following fecal microbiota transplantation for gut microbiota analysis. Also, Aβ pathology, astrocyte and microglia morphology were further explored. Pre-antibiotic-treated mice successfully allowed engraftment of gut microbiota following 7 consecutive days gavage with aged APPSWE/PS1ΔE9 mice microbiota. Microbiota reconstitution by transplantation was largely attributable to the donor source (e.g. g_Coriobacteriaceae and g_Clostridium) and led to a significant increase in Aβ plaques. Surprisingly, astrocyte activation around Aβ plaques was suppressed rather than microglia, the well-recognized plaque phagocytic cell type in Aβ clearance, following microbiota engraftment. Our findings provide a novel framework for understanding the mechanisms of AD through the gut-brain axis and the translation of gut microbiota manipulation from bench to clinical practice.}, }
@article {pmid34108292, year = {2021}, author = {Seo, HS and Chin, HS and Kim, YH and Moon, HS and Kim, K and Nguyen, LP and Yong, D}, title = {Laboratory Aspects of Donor Screening for Fecal Microbiota Transplantation at a Korean Fecal Microbiota Bank.}, journal = {Annals of laboratory medicine}, volume = {41}, number = {6}, pages = {612}, doi = {10.3343/alm.2021.41.6.612}, pmid = {34108292}, issn = {2234-3814}, }
@article {pmid34106090, year = {2021}, author = {Babiker, A and Ingersoll, JM and Adelman, MW and Webster, AS and Broder, KJ and Stittleburg, V and Waggoner, JJ and Kraft, CS and Woodworth, MH}, title = {Validation of High-Sensitivity Severe Acute Respiratory Syndrome Coronavirus 2 Testing for Stool-Toward the New Normal for Fecal Microbiota Transplantation.}, journal = {Clinical and translational gastroenterology}, volume = {12}, number = {6}, pages = {e00363}, pmid = {34106090}, issn = {2155-384X}, support = {P30 AI050409/AI/NIAID NIH HHS/United States ; K23 AI144036/AI/NIAID NIH HHS/United States ; }, mesh = {COVID-19/diagnosis/epidemiology/*transmission/virology ; COVID-19 Testing/*methods/statistics &amp; numerical data ; Centers for Disease Control and Prevention, U.S./standards ; Fecal Microbiota Transplantation/*methods/statistics &amp; numerical data ; Feces/*virology ; Humans ; Nasopharynx/virology ; RNA, Viral/genetics ; Reverse Transcriptase Polymerase Chain Reaction/methods ; SARS-CoV-2/*genetics/isolation &amp; purification ; Tissue Donors/supply &amp; distribution ; United States ; }, abstract = {INTRODUCTION: Mounting evidence demonstrates potential for fecal-oral transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The US Food and Drug Administration now requires SARS-CoV-2 testing of potential feces donors before the use of stool manufactured for fecal microbiota transplantation. We sought to develop and validate a high-sensitivity SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) procedure for testing stool specimens.<br><br>METHODS: A modified extraction method was used with an RT-PCR assay adapted from the Centers for Disease Control and Prevention PCR protocol for respiratory specimens. Contrived specimens were created using pre-COVID-19 banked stool specimens and spiking in known concentrations of SARS-CoV-2-specific nucleic acid. The highest transcript concentration at which 2/2 or 1/2 SARS-CoV-2 targets were detected in 9/10 replicates was defined as the dual-target limit and single-target limit of detection, respectively. The clinical performance of the assay was evaluated with stool samples collected from 17 nasopharyngeal swab RT-PCR-positive patients and 14 nasopharyngeal RT-PCR-negative patients.<br><br>RESULTS: The dual-target and single-target limit of detection were 56 copies/μL and 3 copies/μL, respectively. SARS-CoV-2 was detected at concentrations as low as 0.6 copies/μL. Clinical stool samples from known COVID-19-positive patients demonstrated the detection of SARS-CoV-2 in stool up to 29 days from symptom onset with a high agreement with nasopharyngeal swab tests (kappa statistic of 0.95, P value < 0.001).<br><br>DISCUSSION: The described RT-PCR test is a sensitive and flexible approach for the detection of SARS-CoV-2 in stool specimens. We propose an integrated screening approach that incorporates this stool test to support continuation of fecal microbiota transplantation programs.}, }
@article {pmid34104214, year = {2021}, author = {Gupta, A and Ananthakrishnan, AN}, title = {Economic burden and cost-effectiveness of therapies for Clostridiodes difficile infection: a narrative review.}, journal = {Therapeutic advances in gastroenterology}, volume = {14}, number = {}, pages = {17562848211018654}, pmid = {34104214}, issn = {1756-283X}, abstract = {Clostridioides difficile is the most common cause of healthcare-associated diarrhea. Disease complications as well as recurrent infections contribute significantly to morbidity and mortality. Over the past decades, there has been a rapid increase in the incidence of C. difficile infection (CDI), with a rise in the number of community-acquired cases. CDI has a profound economic impact on both the healthcare system and patients, secondary to recurrences, hospitalization, prolonged length of stay, cost of treatment, and indirect societal costs. With emergence of newer treatment options, the standard of care is shifting from metronidazole and vancomycin towards fidaxomicin and fecal microbiota transplantation (FMT), which despite being more expensive, are more efficacious in preventing recurrences and hence overall are more beneficial forms of therapy per cost-effectiveness analyses. Data regarding preferred route of FMT, timing of FMT, and non-conventional therapies such as bezlotoxumab is scant. There is a need for further studies to elucidate the true attributable costs of CDI as well as continued cost-effectiveness research to reduce the economic burden associated with the disease and improve clinical practice.}, }
@article {pmid34099716, year = {2021}, author = {Choi, BS and Daniel, N and Houde, VP and Ouellette, A and Marcotte, B and Varin, TV and Vors, C and Feutry, P and Ilkayeva, O and Ståhlman, M and St-Pierre, P and Bäckhed, F and Tremblay, A and White, PJ and Marette, A}, title = {Feeding diversified protein sources exacerbates hepatic insulin resistance via increased gut microbial branched-chain fatty acids and mTORC1 signaling in obese mice.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {3377}, pmid = {34099716}, issn = {2041-1723}, support = {FDN-143247//CIHR/Canada ; }, mesh = {Animal Feed/adverse effects ; Animals ; Cell Line, Tumor ; Diet, High-Fat/adverse effects ; Diet, Western/adverse effects ; Dietary Proteins/*adverse effects ; Dietary Sucrose/adverse effects ; Disease Models, Animal ; Fatty Acids/*metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Germ-Free Life ; Gluconeogenesis ; Hepatocytes ; Humans ; *Insulin Resistance ; Liver/metabolism/pathology ; Male ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Mice ; Obesity/*etiology/metabolism/pathology ; Rats ; Ribosomal Protein S6 Kinases, 90-kDa/metabolism ; Signal Transduction ; }, abstract = {Animal models of human diseases are classically fed purified diets that contain casein as the unique protein source. We show that provision of a mixed protein source mirroring that found in the western diet exacerbates diet-induced obesity and insulin resistance by potentiating hepatic mTORC1/S6K1 signaling as compared to casein alone. These effects involve alterations in gut microbiota as shown by fecal microbiota transplantation studies. The detrimental impact of the mixed protein source is also linked with early changes in microbial production of branched-chain fatty acids (BCFA) and elevated plasma and hepatic acylcarnitines, indicative of aberrant mitochondrial fatty acid oxidation. We further show that the BCFA, isobutyric and isovaleric acid, increase glucose production and activate mTORC1/S6K1 in hepatocytes. Our findings demonstrate that alteration of dietary protein source exerts a rapid and robust impact on gut microbiota and BCFA with significant consequences for the development of obesity and insulin resistance.}, }
@article {pmid34096956, year = {2021}, author = {Han, Z and Yao, L and Zhong, Y and Xiao, Y and Gao, J and Zheng, Z and Fan, S and Zhang, Z and Gong, S and Chang, S and Cui, X and Cai, J}, title = {Gut microbiota mediates the effects of curcumin on enhancing Ucp1-dependent thermogenesis and improving high-fat diet-induced obesity.}, journal = {Food &amp; function}, volume = {12}, number = {14}, pages = {6558-6575}, doi = {10.1039/d1fo00671a}, pmid = {34096956}, issn = {2042-650X}, abstract = {Due to extremely poor systemic bioavailability, the mechanism by which curcumin increases energy expenditure remains unelucidated. Accumulating evidence suggests a strong association between the gut microbiota (GM) and energy metabolism. We investigated whether the GM mediates the effects of curcumin on improving energy homeostasis. High-fat diet (HFD)-fed wild type, uncoupling protein 1 (Ucp1) knockout and G protein-coupled membrane receptor 5 (TGR5) knockout mice were treated with curcumin (100 mg kg-1 d-1, p.o.). Curcumin-treated HFD-fed mice displayed decreased body weight gain and augmented cold tolerance due to enhanced adaptive thermogenesis as compared with that in control mice. The anti-obesity effects of curcumin were abolished by Ucp1 knockout. 16S ribosomal DNA sequencing analysis revealed that curcumin restructured the GM in HFD-fed mice. Fecal microbiota transplantation (FMT) and endogenous GM depletion indicated that the GM mediated the enhanced effect of curcumin on Ucp1-dependent thermogenesis. Curcumin altered bile acid (BA) metabolism with increased fractions of circulating deoxycholic acid (DCA) and lithocholic acid (LCA), which are the two most potent ligands for TGR5. Consistently, the enhanced effect of curcumin on Ucp1-dependent thermogenesis was eliminated by TGR5 knockout. Curcumin requires the GM and TGR5 to activate the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway in thermogenic adipose tissue. Here, we demonstrated that the GM mediates the effects of curcumin on enhancing Ucp1-dependent thermogenesis and ameliorating HFD-induced obesity by influencing BA metabolism. We disclosed the potential of nutritional and pharmacologic manipulations of the GM to enhance Ucp1-dependent thermogenesis in the prevention and treatment of obesity.}, }
@article {pmid34093740, year = {2021}, author = {Fu, Y and Luo, Y and Grinspan, AM}, title = {Epidemiology of community-acquired and recurrent Clostridioides difficile infection.}, journal = {Therapeutic advances in gastroenterology}, volume = {14}, number = {}, pages = {17562848211016248}, pmid = {34093740}, issn = {1756-283X}, abstract = {Clostridioides difficile infection is a leading cause of healthcare-associated infections with significant morbidity and mortality. For the past decade, the bulk of infection prevention and epidemiologic surveillance efforts have been directed toward mitigating hospital-acquired C. difficile. However, the incidence of community-associated infection is on the rise. Patients with community-associated C. difficile tend to be younger and have lower mortality rate. Rates of recurrent C. difficile infection overall have decreased in the United States, but future research and public health endeavors are needed to standardize and improve disease detection, stratify risk factors in large-scale population studies, and to identify regional and local variations in strain types, reservoirs and transmission routes to help characterize and combat the changing epidemiology of C. difficile.}, }
@article {pmid34092246, year = {2021}, author = {Wu, Y and He, F and Zhang, C and Zhang, Q and Su, X and Zhu, X and Liu, A and Shi, W and Lin, W and Jin, Z and Yang, H and Lin, J}, title = {Melatonin alleviates titanium nanoparticles induced osteolysis via activation of butyrate/GPR109A signaling pathway.}, journal = {Journal of nanobiotechnology}, volume = {19}, number = {1}, pages = {170}, pmid = {34092246}, issn = {1477-3155}, support = {81871789//National Natural Science Foundation of China/ ; 31771063//National Natural Science Foundation of China (CN)/ ; 81802200//National Natural Science Foundation of China (CN)/ ; 82171333//National Natural Science Foundation of China (CN)/ ; 82101033//National Natural Science Foundation of China (CN)/ ; BK20180052//Natural Science Foundation of Jiangsu Province (CN)/ ; GSWS2020023//Gusu Health Talents Program/ ; }, abstract = {BACKGROUND: Inflammatory osteolysis after total joint replacement (TJR) may cause implant failure, periprosthetic fractures, and be a severe threat to global public health. Our previous studies demonstrated that melatonin had a therapeutic effect on wear-particles induced osteolysis. Gut microbiota is closely related to bone homeostasis, and has been proven to be affected by melatonin. However, whether melatonin could play its anti-osteolysis effects through reprogramming gut microbiota remains elusive.<br><br>RESULTS: Here, we demonstrated that melatonin could alleviate Ti-particles induced osteolysis, while this therapeutic effect was blocked by antibiotic cocktail treatment. Interestingly, transplantation of fecal microbiota from mice treated with melatonin reappeared the same beneficial effect. Analysis of the 16S rRNA revealed that melatonin could reverse dysbacteriosis triggered by osteolysis, and elevate the relative abundance of some short chain fatty acid (SCFA) producing bacteria. Moreover, butyrate was enriched by exogenous melatonin administration, while acetate and propionate did not show an evident difference. This was consistent with the results of the metagenomic approach (PICRUSt2) analysis, which revealed a general increase in the synthetic enzymes of butyrate. More importantly, direct supplementation of butyrate could also recapitulate the anti-osteolysis effect of melatonin. Further analysis identified that butyrate alleviated osteolysis via activating its receptor GPR109A, and thus to suppress the activation of NLRP3 inflammasome triggered by Ti-particles.<br><br>CONCLUSIONS: Taken together, our results suggested that the benefits of melatonin mainly depend on the ability of modulating gut microbiota and regulating butyrate production.}, }
@article {pmid34090885, year = {2021}, author = {Ianiro, G and Giambò, F and Cammarota, G}, title = {Residual Gastrointestinal Symptoms after Fecal Microbiota Transplantation for Clostridioides difficile Infection: A Matter of Efficacy Rather Than Safety?.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2021.06.002}, pmid = {34090885}, issn = {1528-0012}, }
@article {pmid34089791, year = {2021}, author = {Wang, J and Zheng, S and Yang, X and Huazeng, B and Cheng, Q}, title = {Influences of non-IgE-mediated cow's milk protein allergy-associated gut microbial dysbiosis on regulatory T cell-mediated intestinal immune tolerance and homeostasis.}, journal = {Microbial pathogenesis}, volume = {158}, number = {}, pages = {105020}, doi = {10.1016/j.micpath.2021.105020}, pmid = {34089791}, issn = {1096-1208}, abstract = {Gut microbial dysbiosis is closely associated with cow's milk protein allergy (CMPA) during infancy. Recent research has highlighted the crucial role of the commensal microbiota-induced intestinal regulatory T (Treg) cell response in the development of oral tolerance and protection against IgE-mediated food allergies. However, the influences of CMPA (particularly non-IgE-mediated CMPA)-associated microbial dysbiosis on Treg cell-mediated intestinal immune tolerance and homeostasis remain poorly characterized. To investigate this issue, fecal microbiota from infant donors with food protein-induced allergic proctocolitis (FPIAP) associated with cow's milk, which is the most frequent clinical type of non-IgE-mediated gastrointestinal CMPA, and from age-matched healthy controls were transplanted into germ-free mice in this study. Two weeks post fecal microbiota transplantation, the gut microbiome of the recipient mice was analyzed by 16S rRNA gene sequencing, and the intestinal immunological alterations associated with the Treg cell compartment and intestinal immune homeostasis were detected. The specific gut microbial phylotypes that were potentially responsible for the disruption of intestinal immune homeostasis were also analyzed. We observed that the main characteristics of the gut microbiome in infant donors could be stably maintained in recipient mice. We also found that mice colonized with the gut microbiome from infants with cow's milk-induced FPIAP showed significant deficiencies in the accumulation and function of intestinal Treg cells. Furthermore, these mice showed disrupted intestinal immune homeostasis, which was characterized by an overactivated Th2 biased immune response. We further identified two potentially pathogenic genera that contribute to this disruption. Overall, our results highlight a destructive effect of non-IgE-mediated CMPA-associated microbial dysbiosis on intestinal immune tolerance and homeostasis. We believe these findings will help improve our understanding of the gut microbiota-mediated pathogenesis of non-IgE-mediated CMPA in the future.}, }
@article {pmid34089134, year = {2021}, author = {Mendelsohn, RB and Kaltsas, A and King, S and Hwang, C and Kassam, Z and Abend, AM and Kramer, E and Kamboj, M}, title = {Fecal Microbiota Transplantation Is Safe for Clostridiodies difficile Infection in Patients with Solid Tumors Undergoing Chemotherapy.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, pmid = {34089134}, issn = {1573-2568}, abstract = {BACKGROUND: Recurrent Clostridiodies difficile infection (CDI) contributes to morbidity and mortality in cancer patients. Fecal microbiota transplantation (FMT) has been proven to be effective in treatment of recurrent CDI, but immunocompromised patients have been excluded from prospective studies due to safety concerns. The aim of this study was to investigate the safety of FMT for recurrent CDI in immunocompromised patients with solid tumor malignancy undergoing chemotherapy.<br><br>METHODS: This was a single center, prospective observational study of patients at a tertiary care cancer center of 10 patients with recurrent CDI who were at least 18 years of age, with a solid tumor malignancy who had received chemotherapy within the previous 6 months. Patients received FMT either by upper endoscopy or colonoscopy and were followed for 6 months. Safety was a primary outcome measured by infections occurring within 2 weeks of FMT. Efficacy of FMT was also evaluated.<br><br>RESULTS: Nineteen patients were evaluated. On applying exclusion criteria, 10 were included in the study. One patient requested to be off study within 2 weeks and was considered a treatment failure. Seven received FMT via upper endoscopy, three via colonoscopy. There were no infectious complications from FMT. Eight patients (80%) were cured after the first FMT. All eight patients went on to restart oncologic treatment with an average of 32.5 days after FMT.<br><br>CONCLUSIONS: FMT is safe and effective for recurrent CDI in solid tumor patients undergoing chemotherapy. Patients can resume oncologic treatment after FMT.}, }
@article {pmid34088413, year = {2021}, author = {Khanna, S and Tande, A and Rubin, DT and Khoruts, A and Kahn, SA and Pardi, DS}, title = {Fecal Microbiota Transplantation for Recurrent C difficile Infection During the COVID-19 Pandemic: Experience and Recommendations.}, journal = {Mayo Clinic proceedings}, volume = {96}, number = {6}, pages = {1418-1425}, pmid = {34088413}, issn = {1942-5546}, support = {R24 AI118629/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; COVID-19/diagnosis/*epidemiology/prevention &amp; control ; *Clostridioides difficile ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation/adverse effects/methods ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; SARS-CoV-2 ; Young Adult ; }, abstract = {OBJECTIVE: To report experience with fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (rCDI) and provide recommendations for management of rCDI and donor testing during the COVID-19 pandemic.<br><br>METHODS: A retrospective study of patients with rCDI who underwent FMT from May 26, 2020, to September 30, 2020, with stool from well-screened donors with health and infectious screening and a newly implemented strategy for COVID-19 screening with every 2-week bookend testing with stool quarantine. Patients were followed up for development of rCDI and COVID-19.<br><br>RESULTS: Of the 57 patients who underwent FMT for rCDI, 29 were tested for COVID-19 via nasopharyngeal polymerase chain reaction (PCR) and 22 via serology. All results were negative, except for 1 positive serology. Donor testing every 2 weeks for COVID-19 via serology and nasopharyngeal swab PCR was negative, except for 2 donors at 1 center who were excluded. Three patients had rCDI after FMT, and 1 underwent repeat FMT. One patient developed respiratory symptoms suggestive of COVID-19 and tested negative via nasopharyngeal PCR. Eleven patients who underwent COVID-19 testing for elective procedures or hospitalizations tested negative. No SARS-CoV-2 transmission was noted.<br><br>CONCLUSIONS: With appropriate donor screening, FMT can be performed safely for rCDI during the COVID-19 pandemic. Development of a validated stool assay for SARS-CoV-2 will simplify this process further.}, }
@article {pmid34087350, year = {2021}, author = {Li, Q and Cui, Y and Xu, B and Wang, Y and Lv, F and Li, Z and Li, H and Chen, X and Peng, X and Chen, Y and Wu, E and Qu, D and Jian, Y and Si, H}, title = {Main active components of Jiawei Gegen Qinlian decoction protects against ulcerative colitis under different dietary environments in a gut microbiota-dependent manner.}, journal = {Pharmacological research}, volume = {170}, number = {}, pages = {105694}, doi = {10.1016/j.phrs.2021.105694}, pmid = {34087350}, issn = {1096-1186}, abstract = {As an effective drug against acute enteritis diarrhea, Gegen Qinlian decoction (GQD) has a history of 2000 years. However, the potential molecular mechanism through which GQD could protect intestinal barrier from ulcerative colitis (UC) still remains undefined. As an important part of the homeostasis of the colon, gut microbiota is closely related to the dynamic evolution of the surrounding environment and the adjustment of dietary structure. At present, the effectiveness and mechanism of Jiawei Gegen Qinlian decoction against UC in different dietary environments are not clear. Here, the main active components of Jiawei Gegen Qinlian Decoction (PBM), were selected to construct a reasonable and effective compound scheme. We adopted "5% dextran sulfate sodium (DSS)" and "high temperature and humidity + high sugar and high fat + alcohol + 5%DSS" to induce UC rat models in general environment and UC rat models in Lingnan area, respectively. Then, we examined the therapeutic effects of PBM (89.96 mg/kg and 179.92 mg/kg) on two kinds of UC rats. The role of gut microbiota in the anti-UC effect of PBM was identified by intestinal flora consumption and fecal microbiota transplantation (FMT) experiments. Subsequently, we monitored the alterations of gut microbiota and fecal metabolism in the rat colon by 16Sr DNA technique and targeted metabonomics, respectively. The colon inflammation of the PBM-treated and the FMT-treated rats both showed significant relief, as evidenced by a reduction in body weight loss, bloody stool, diarrhea, disease activity index (DAI) score, shortening of colon length as well as decreased colon histology damage. Interestingly enough, the depletion of intestinal flora took away the protective effect of PBM, confirming the importance of intestinal flora in the anti-UC effect of PBM. Then our findings suggested that PBM could not only regulate the gut microbiota by increasing Akkermansia and Romboutsia but also decrease Escherichia-Shigella. More importantly, PBM could increase the production of propionate and total short-chain fatty acids (SCFAs) in colitis rats, regulate medium and long chain fatty acids (M-LCFAs), maintain bile acids (BAs) homeostasis, and regulate amino acids (AAs) metabolism. The transformation of intestinal environment might be related to the upregulation of anti-inflammation, anti-oxidation and tight junction protein expression in colonic mucosa. In summary, PBM showed potential for anti-UC activity through gut microbiota dependence and was expected to be a complementary and alternative medicine herb therapy.}, }
@article {pmid34086219, year = {2021}, author = {Müssig, K}, title = {.}, journal = {MMW Fortschritte der Medizin}, volume = {163}, number = {11}, pages = {26-27}, doi = {10.1007/s15006-021-0069-3}, pmid = {34086219}, issn = {1613-3560}, mesh = {Body Weight ; *Diet ; *Fecal Microbiota Transplantation ; Humans ; Weight Gain ; }, }
@article {pmid34079458, year = {2021}, author = {Li, Q and Ding, X and Liu, Y and Marcella, C and Dai, M and Zhang, T and Bai, J and Xiang, L and Wen, Q and Cui, B and Zhang, F}, title = {Fecal Microbiota Transplantation is a Promising Switch Therapy for Patients with Prior Failure of Infliximab in Crohn's Disease.}, journal = {Frontiers in pharmacology}, volume = {12}, number = {}, pages = {658087}, pmid = {34079458}, issn = {1663-9812}, abstract = {Background: How to handle patients with anti-tumor necrosis factor (anti-TNF) failure was a common challenge to clinicians in Crohn's disease (CD). The present study is dedicated to clarifying whether fecal microbiota transplantation (FMT) could be a switch therapy for patients with prior failure of infiiximab (IFX) in CD in a long-term observation. Methods: Thirty-six patients with CD who had prior failure of IFX were recruited from January 2013 to December 2019. The "one-hour FMT protocol" was followed in all patients. All patients received the first course of FMT through gastroscopy or mid-gut transendoscopic enteral tubing. After April 2014, the methodology of FMT was coined as washed microbiota transplantation (WMT), substituting for the manual methods, which is dependent on the automatic microbiota purification system and the washing process. The primary endpoint of this study was the clinical remission at one month and one year after FMT. The secondary endpoint was the safety of FMT in the short and long term, and clinical factors as predictors for long-term efficacy of FMT. Clinical factors as independent predictors of efficacy from FMT were isolated using univariable and multivariable logistic regression analysis. Results: There was no significant difference in the rates of clinical response and remission between IFX treatment stage and FMT treatment stage (at one month, three months and six months after administration) (p > 0.05). Compared with those of 19 patients who achieved clinical remission at one month after FMT, the rates of clinical relapse were significantly higher in 18 patients who achieved clinical remission at one month after IFX [log-rank test p = 0.0009 HR = 3.081 (95% CI 1.43-6.639)]. Multivariate analysis revealed that the gender of donor (95% CI: 0.001-0.72; p = 0.031) was an independent predictor of efficacy at one year after FMT. No serious adverse events (AEs) associated with FMT were observed during and after FMT. The rate of AEs was significantly lower in group FMT than that in group IFX (p = 0.002). Conclusion: The present findings first time provided the evidence for clinicians to consider FMT into practice as an alternative switch therapy for patients with prior loss of response or intolerance to IFX in CD. Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT01793831.}, }
@article {pmid34078971, year = {2021}, author = {Skaarud, KJ and Hov, JR and Hansen, SH and Kummen, M and Valeur, J and Seljeflot, I and Bye, A and Paulsen, V and Lundin, KEA and Trøseid, M and Tjønnfjord, GE and Iversen, PO}, title = {Mortality and microbial diversity after allogeneic hematopoietic stem cell transplantation: secondary analysis of a randomized nutritional intervention trial.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {11593}, pmid = {34078971}, issn = {2045-2322}, abstract = {Gut mucosal barrier injury is common following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and associated with poor clinical outcomes. Diet is critical for microbial diversity, but whether nutritional support affects microbiota and outcome after allo-HSCT is unknown. We present a secondary analysis of a randomized controlled nutritional intervention trial during allo-HSCT. We investigated if the intervention influenced gut microbiota, short-chain fatty acids (SCFAs), and markers of gut barrier functions, and if these parameters were associated with clinical outcomes. Fecal specimens were available from 47 recipients, and subjected to 16S rRNA gene sequencing. We found no significant differences between the intervention group and controls in investigated parameters. We observed a major depletion of microbiota, SCFAs, and altered markers of gut barrier function from baseline to 3 weeks post-transplant. One-year mortality was significantly higher in patients with lower diversity at 3 weeks post-HSCT, but not related to diversity at baseline. The relative abundance of Blautia genus at 3 weeks was higher in survivors. Fecal propionic acid was associated with survival. Markers of gut barrier functions were less strongly associated with clinical outcomes. Possibly, other strategies than dietary intervention are needed to prevent negative effects of gut microbiota and clinical outcomes after allo-HSCT.ClinicalTrials.gov (NCT01181076).}, }
@article {pmid34077717, year = {2021}, author = {Hanssen, NMJ and de Vos, WM and Nieuwdorp, M}, title = {Fecal microbiota transplantation in human metabolic diseases: From a murky past to a bright future?.}, journal = {Cell metabolism}, volume = {33}, number = {6}, pages = {1098-1110}, doi = {10.1016/j.cmet.2021.05.005}, pmid = {34077717}, issn = {1932-7420}, abstract = {Fecal microbiota transplantation (FMT) is gaining considerable traction as a therapeutic approach to influence the course of a plethora of chronic conditions, ranging from metabolic syndrome and malignancies to auto-immune and neurological diseases, and helped to establish the contribution of the gut microbiome to these conditions. Although FMT procedures have yielded important mechanistic insights, their use in clinical practice may be limited due to practical objections in the setting of metabolic diseases. While its applicability is established to treat recurrent Clostridiodes difficile, FMT is emerging in ulcerative colitis and various other diseases. A particularly new insight is that FMTs may not only alter insulin sensitivity but may also alter the course of type 1 diabetes by attenuating underlying auto-immunity. In this review, we will outline the major principles and pitfalls of FMT and where optimization of study design and the procedure itself will further advance the field of cardiometabolic medicine.}, }
@article {pmid34074837, year = {2021}, author = {Craven, LJ and Parvathy, SN and Burton, JP and Silverman, MS}, title = {Response to Ianiro et al.}, journal = {The American journal of gastroenterology}, volume = {116}, number = {6}, pages = {1361-1362}, doi = {10.14309/ajg.0000000000001160}, pmid = {34074837}, issn = {1572-0241}, mesh = {Fecal Microbiota Transplantation ; Humans ; *Non-alcoholic Fatty Liver Disease ; Permeability ; }, }
@article {pmid34074836, year = {2021}, author = {Ianiro, G and Porcari, S and Gasbarrini, A and Cammarota, G}, title = {Quantity of Donor Stool for Fecal Microbiota Transplantation: The More, the Better?.}, journal = {The American journal of gastroenterology}, volume = {116}, number = {6}, pages = {1360-1361}, doi = {10.14309/ajg.0000000000001130}, pmid = {34074836}, issn = {1572-0241}, mesh = {*Clostridium Infections ; Fecal Microbiota Transplantation ; Feces ; Humans ; *Non-alcoholic Fatty Liver Disease ; Permeability ; }, }
@article {pmid34074214, year = {2021}, author = {Browne, PD and Cold, F and Petersen, AM and Halkjær, SI and Christensen, AH and Günther, S and Hestbjerg Hansen, L}, title = {Engraftment of strictly anaerobic oxygen-sensitive bacteria in irritable bowel syndrome patients following fecal microbiota transplantation does not improve symptoms.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1-16}, pmid = {34074214}, issn = {1949-0984}, abstract = {Dysbiosis of the gut microbiome has been correlated with irritable bowel syndrome (IBS). Fecal microbiota transplantation (FMT) is being explored as a therapeutic option. Little is known of the mechanisms of engraftment of microbes following FMT and whether the engraftment of certain microbes correlate with clinical improvement in IBS. Microbiome data, from a previously reported placebo-controlled trial of treatment of IBS with FMT or placebo capsules, were used to investigate microbial engraftment 15 days, 1, 3 and 6 months after treatment through assessment of gains, losses and changes in abundance of amplicon sequence variants (ASVs) and microbial diversity (CHAO-1 richness) between the FMT group and the placebo group. These data were compared to changes in IBS Symptom Severity Scores (IBS-SSS). Twelve days of treatment with 25 daily multi-donor FMT capsules induced significant short- and long-term changes in the recipients' microbiomes for at least 6 months, with persistent engraftment of a variety of anaerobic bacteria from keystone genera, such as Faecalibacterium, Prevotella and Bacteroides and increased microbial diversity, particularly in patients with low initial diversity. FMT recipients lost ASVs after treatment, which was seen to a much lesser extent in the placebo group. No ASVs increased to a greater extent between FMT responders and non-responders following treatment. Major long-term changes, lasting for at least 6 months, in the gut microbiomes of IBS patients are seen following treatment with FMT capsules. None of these changes correlated with clinical improvement. The relationship between the microbiome and the etiology of IBS still remains unsolved.}, }
@article {pmid34073695, year = {2021}, author = {Chiu, CW and Tsai, PJ and Lee, CC and Ko, WC and Hung, YP}, title = {Application of Microbiome Management in Therapy for Clostridioides difficile Infections: From Fecal Microbiota Transplantation to Probiotics to Microbiota-Preserving Antimicrobial Agents.}, journal = {Pathogens (Basel, Switzerland)}, volume = {10}, number = {6}, pages = {}, pmid = {34073695}, issn = {2076-0817}, support = {MOHW105-CDC-C-114-122113//Ministry of Health and Welfare/ ; MOST 108-2321-B-006-004 and 109-2314-B-006-089-MY//Ministry of Science and Technology/ ; NCKUH-11004029//National Cheng Kung University Hospital/ ; }, abstract = {Oral vancomycin and metronidazole, though they are the therapeutic choice for Clostridioides difficile infections (CDIs), also markedly disturb microbiota, leading to a prolonged loss of colonization resistance to C. difficile after therapy; as a result, their use is associated with a high treatment failure rate and high recurrent rate. An alternative for CDIs therapy contains the delivery of beneficial (probiotic) microorganisms into the intestinal tract to restore the microbial balance. Recently, mixture regimens containing Lactobacillus species, Saccharomyces boulardii, or Clostridium butyricum have been extensively studied for the prophylaxis of CDIs. Fecal microbiota transplantation (FMT), the transfer of (processed) fecal material from healthy donors to patients for treating CDIs, combined with vancomycin was recommended as the primary therapy for multiple recurrent CDIs (rCDIs). Either probiotics or FMT have been utilized extensively in preventing or treating CDIs, aiming at less disturbance in the microbiota to prevent rCDIs after therapy cessation. Otherwise, many newly developed therapeutic agents have been developed and aim to preserve microbiota during CDI treatment to prevent disease recurrence and might be useful in clinical patients with rCDIs in the future.}, }
@article {pmid34071229, year = {2021}, author = {Shang, L and Liu, H and Yu, H and Chen, M and Yang, T and Zeng, X and Qiao, S}, title = {Core Altered Microorganisms in Colitis Mouse Model: A Comprehensive Time-Point and Fecal Microbiota Transplantation Analysis.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {10}, number = {6}, pages = {}, pmid = {34071229}, issn = {2079-6382}, support = {2016YFD0501308//National Key Research and Development Program of China/ ; cstc2019ngzx0019//Chongqing Rongchang Agricultural and Animal Husbandry High-tech Industry Research and Development Project/ ; }, abstract = {Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic and relapsing inflammation within the gastrointestinal tract. Antibiotics have been used to treat IBD, primarily utilizing metronidazole. Although there does seem to be a treatment effect, the broad-spectrum antibiotics that have been used to date are crude tools and have many adverse effects. Available evidence suggests that the host microbiome is implicated in the pathogenesis of IBD, though the key bacteria remain unknown. If the bacterial population can be modified appropriately, the use of antibiotics will have a better therapeutic effect. In this study, mice were fed dextran sodium sulfate (DSS) solution for 5 days, followed by 5 days of normal drinking water, to investigate the gut microbiota response to colitis and the initial alteration of microbiota in recovery phase. Day 0 was considered the normal control, while day 5 and day 10 were considered the colitis mouse model progressive phase and recovery phase, respectively. Results showed that inflammation could induce proportional changes in the gut microbiota. Furthermore, transplanting the microbiota in progressive phase to antibiotic-induced microbiota-depleted mice could induce inflammation similar to colitis, which proves the importance of initial alteration of the microbiota for IBD recovery and the potential of the microbiota as a target for the treatment of IBD. Meanwhile, we have also identified three possible target microorganisms in the development of colitis, namely genera Muribaculaceae (negative correlation), Turicibacter (positive correlation) and Lachnospiraceae (negative correlation) in inflammation status through comprehensive analysis.}, }
@article {pmid34071065, year = {2021}, author = {LeBlanc, JF and Segal, JP and de Campos Braz, LM and Hart, AL}, title = {The Microbiome as a Therapy in Pouchitis and Ulcerative Colitis.}, journal = {Nutrients}, volume = {13}, number = {6}, pages = {}, pmid = {34071065}, issn = {2072-6643}, mesh = {Colitis, Ulcerative/microbiology/*therapy ; Diet, Mediterranean ; Fatty Acids, Omega-3/therapeutic use ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/therapy ; Microbiota ; Pouchitis/microbiology/*therapy ; Prebiotics/administration &amp; dosage ; Probiotics/therapeutic use ; }, abstract = {The gut microbiome has been implicated in a range of diseases and there is a rapidly growing understanding of this ecosystem's importance in inflammatory bowel disease. We are yet to identify a single microbe that causes either ulcerative colitis (UC) or pouchitis, however, reduced microbiome diversity is increasingly recognised in active UC. Manipulating the gut microbiome through dietary interventions, prebiotic and probiotic compounds and faecal microbiota transplantation may expand the therapeutic landscape in UC. Specific diets, such as the Mediterranean diet or diet rich in omega-3 fatty acids, may reduce intestinal inflammation or potentially reduce the risk of incident UC. This review summarises our knowledge of gut microbiome therapies in UC and pouchitis.}, }
@article {pmid34068085, year = {2021}, author = {Haindl, R and Engel, J and Kulozik, U}, title = {Establishment of an In Vitro System of the Human Intestinal Microbiota: Effect of Cultivation Conditions and Influence of Three Donor Stool Samples.}, journal = {Microorganisms}, volume = {9}, number = {5}, pages = {}, pmid = {34068085}, issn = {2076-2607}, abstract = {Fecal microbiota transplantation (FMT) is an alternative method for the treatment of gastrointestinal diseases with a high recovery rate. Disadvantages are ethical concerns, high donor requirements and the low storability of stool samples. The cultivation of an in vitro microbiota in a continuous bioreactor was established as an alternative to FMT to overcome these problems. In this study, the influence of the system parameters and donor stool characteristics was investigated. Each continuous colonic fermentation system was inoculated with feces from three different donors until a stable state was established. The influence of the fermentation conditions on the system's behavior regarding cell count, metabolic activity, short-chain fatty acid profile and microbiota composition as well as richness and diversity was assessed. Cultivation conditions were found to affect the microbial system: the number of cells and the production of short-chain fatty acids increased. The abundance of Actinobacteria and Firmicutes decreased, Bacteroidetes increased, while Proteobacteria and Verrucomicrobia remained largely unaffected. Diversity in the in vitro system decreased, but richness was unaffected. The cultivation of stool from different donors revealed that the performance of the created in vitro system was similar and comparable, but unique characteristics of the composition of the original stool remained.}, }
@article {pmid34061595, year = {2021}, author = {Sato, K and Yamazaki, K and Kato, T and Nakanishi, Y and Tsuzuno, T and Yokoji-Takeuchi, M and Yamada-Hara, M and Miura, N and Okuda, S and Ohno, H and Yamazaki, K}, title = {Obesity-Related Gut Microbiota Aggravates Alveolar Bone Destruction in Experimental Periodontitis through Elevation of Uric Acid.}, journal = {mBio}, volume = {12}, number = {3}, pages = {e0077121}, pmid = {34061595}, issn = {2150-7511}, abstract = {Obesity is a risk factor for periodontal disease (PD). Initiation and progression of PD are modulated by complex interactions between oral dysbiosis and host responses. Although obesity is associated with increased susceptibility to bacterial infection, the detailed mechanisms that connect obesity and susceptibility to PD remain elusive. Using fecal microbiota transplantation and a ligature-induced PD model, we demonstrated that gut dysbiosis-associated metabolites from high-fat diet (HFD)-fed mice worsen alveolar bone destruction. Fecal metabolomics revealed elevated purine degradation pathway activity in HFD-fed mice, and recipient mice had elevated levels of serum uric acid upon PD induction. Furthermore, PD induction caused more severe bone destruction in hyperuricemic than normouricemic mice, and the worsened bone destruction was completely abrogated by allopurinol, a xanthine oxidase inhibitor. Thus, obesity increases the risk of PD by increasing production of uric acid mediated by gut dysbiosis. IMPORTANCE Obesity is an epidemic health issue with a rapid increase worldwide. It increases the risk of various diseases, including periodontal disease, an oral chronic infectious disease. Although obesity increases susceptibility to bacterial infection, the precise biological mechanisms that link obesity and susceptibility to periodontal disease remain elusive. Using fecal microbial transplantation, experimental periodontitis, and metabolomics, our study demonstrates uric acid as a causative substance for greater aggravation of alveolar bone destruction in obesity-related periodontal disease. Gut microbiota from obese mice upregulated the purine degradation pathway, and the resulting elevation of serum uric acid promoted alveolar bone destruction. The effect of uric acid was confirmed by administration of allopurinol, an inhibitor of xanthine oxidase. Overall, our study provides new insights into the pathogenic mechanisms of obesity-associated periodontal disease and the development of new therapeutic options for the disease.}, }
@article {pmid34058102, year = {2021}, author = {Horton, LC and Feuerstein, JD}, title = {In recurrent C difficile infection, oral FMT capsules have a pooled cure rate of 82% (low-quality evidence).}, journal = {Annals of internal medicine}, volume = {174}, number = {6}, pages = {JC65}, doi = {10.7326/ACPJ202106150-065}, pmid = {34058102}, issn = {1539-3704}, mesh = {Capsules ; *Clostridium Infections/therapy ; *Fecal Microbiota Transplantation ; Humans ; Recurrence ; Treatment Outcome ; }, abstract = {SOURCE CITATION: Du C, Luo Y, Walsh S, Grinspan A. Oral fecal microbiota transplant capsules are safe and effective for recurrent Clostridioides difficile infection: a systematic review and meta-analysis. J Clin Gastroenterol. 2021;55:300-8. 33471490.}, }
@article {pmid34055657, year = {2021}, author = {Mazzawi, T and El-Salhy, M and Lied, GA and Hausken, T}, title = {The Effects of Fecal Microbiota Transplantation on the Symptoms and the Duodenal Neurogenin 3, Musashi 1, and Enteroendocrine Cells in Patients With Diarrhea-Predominant Irritable Bowel Syndrome.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {524851}, pmid = {34055657}, issn = {2235-2988}, mesh = {Diarrhea ; Duodenum ; Enteroendocrine Cells ; *Fecal Microbiota Transplantation ; Feces ; Female ; Humans ; *Irritable Bowel Syndrome/therapy ; Male ; Norway ; }, abstract = {Introduction: Interactions between the gut microbiota and enteroendocrine cells play important role in irritable bowel syndrome (IBS). Reduced stem cell densities and their differentiation into enteroendocrine cells may cause abnormal densities of the duodenal enteroendocrine cells in IBS patients.<br><br>Materials and Methods: We aimed to investigate the effects of fecal microbiota transplantation (FMT) on stem cell differentiation into enteroendocrine cells as detected by neurogenin 3, stem cells as detected by Musashi 1, and the enteroendocrine cells in the duodenum of IBS patients. The study included 16 IBS patients according to Rome III criteria. Four patients were excluded. The remaining patients (n = 12, four females and eight males) were divided according to the cause of IBS into post-infectious (n = 6) and idiopathic (n = 6) IBS. They completed the following questionnaires before and 3 weeks after FMT: IBS-Symptom Severity Scoring system (IBS-SSS) and IBS-Symptom Questionnaire (IBS-SQ). Feces donated by healthy relatives of the patients were transplanted via gastroscope. Biopsies were taken from the descending part of the duodenum at baseline and 3 weeks after FMT. They were immunostained for neurogenin 3, Musashi 1, and all types of duodenal enteroendocrine cells and quantified by computerized image analysis. Microbiota analyses of feces collected just before and 3 weeks after FMT were performed using GA-map™ Dysbiosis test (Genetic Analysis AS, Oslo, Norway).<br><br>Results: The total scores for IBS-SSS and IBS-SQ were significantly improved 3 weeks after receiving FMT, P = 0.0009 and <0.0001, respectively. The stem cell densities of neurogenin 3 increased significantly following FMT (P = 0.0006) but not for Musashi 1 (P = 0.42). The cell densities of chromogranin A, cholecystokinin, gastric inhibitory peptide, serotonin, and somatostatin, but not for secretin, have significantly changed in both IBS groups after 3 weeks from receiving FMT.<br><br>Conclusion: More than two-thirds of IBS patients experienced improvement in their symptoms parallel to changes in the enteroendocrine cells densities 3 weeks after FMT. The changes in the enteroendocrine cell densities do not appear to be caused by changes in the stem cells or their early progenitors rather by changes in the differentiation progeny as detected by neurogenin 3. The study was retrospectively registered at ClinicalTrials.gov (ID: NCT03333291).<br><br>Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03333291.}, }
@article {pmid34054866, year = {2021}, author = {Yang, M and Yang, Y and He, Q and Zhu, P and Liu, M and Xu, J and Zhao, M}, title = {Intestinal Microbiota-A Promising Target for Antiviral Therapy?.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {676232}, pmid = {34054866}, issn = {1664-3224}, mesh = {Animals ; Anti-Bacterial Agents/*therapeutic use ; Antiviral Agents/*therapeutic use ; COVID-19/*therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology ; Host-Pathogen Interactions ; Humans ; Probiotics/*therapeutic use ; SARS-CoV-2/*physiology ; Virus Diseases/*therapy ; }, abstract = {The intestinal microbiota is thought to be an important biological barrier against enteric pathogens. Its depletion, however, also has curative effects against some viral infections, suggesting that different components of the intestinal microbiota can play both promoting and inhibitory roles depending on the type of viral infection. The two primary mechanisms by which the microbiota facilitates or inhibits viral invasion involve participation in the innate and adaptive immune responses and direct or indirect interaction with the virus, during which the abundance and composition of the intestinal microbiota might be changed by the virus. Oral administration of probiotics, faecal microbiota transplantation (FMT), and antibiotics are major therapeutic strategies for regulating intestinal microbiota balance. However, these three methods have shown limited curative effects in clinical trials. Therefore, the intestinal microbiota might represent a new and promising supplementary antiviral therapeutic target, and more efficient and safer methods for regulating the microbiota require deeper investigation. This review summarizes the latest research on the relationship among the intestinal microbiota, anti-viral immunity and viruses and the most commonly used methods for regulating the intestinal microbiota with the goal of providing new insight into the antiviral effects of the gut microbiota.}, }
@article {pmid34054845, year = {2021}, author = {Bosák, J and Lexa, M and Fiedorová, K and Gadara, DC and Micenková, L and Spacil, Z and Litzman, J and Freiberger, T and Šmajs, D}, title = {Patients With Common Variable Immunodeficiency (CVID) Show Higher Gut Bacterial Diversity and Levels of Low-Abundance Genes Than the Healthy Housemates.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {671239}, pmid = {34054845}, issn = {1664-3224}, abstract = {Common variable immunodeficiency (CVID) is a clinically and genetically heterogeneous disorder with inadequate antibody responses and low levels of immunoglobulins including IgA that is involved in the maintenance of the intestinal homeostasis. In this study, we analyzed the taxonomical and functional metagenome of the fecal microbiota and stool metabolome in a cohort of six CVID patients without gastroenterological symptomatology and their healthy housemates. The fecal microbiome of CVID patients contained higher numbers of bacterial species and altered abundance of thirty-four species. Hungatella hathewayi was frequent in CVID microbiome and absent in controls. Moreover, the CVID metagenome was enriched for low-abundance genes likely encoding nonessential functions, such as bacterial motility and metabolism of aromatic compounds. Metabolomics revealed dysregulation in several metabolic pathways, mostly associated with decreased levels of adenosine in CVID patients. Identified features have been consistently associated with CVID diagnosis across the patients with various immunological characteristics, length of treatment, and age. Taken together, this initial study revealed expansion of bacterial diversity in the host immunodeficient conditions and suggested several bacterial species and metabolites, which have potential to be diagnostic and/or prognostic CVID markers in the future.}, }
@article {pmid34051351, year = {2021}, author = {Pandya, G and Kirtonia, A and Singh, A and Goel, A and Mohan, CD and Rangappa, KS and Pandey, AK and Kapoor, S and Tandon, S and Sethi, G and Garg, M}, title = {A comprehensive review of the multifaceted role of the microbiota in human pancreatic carcinoma.}, journal = {Seminars in cancer biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.semcancer.2021.05.027}, pmid = {34051351}, issn = {1096-3650}, abstract = {Pancreatic carcinoma is associated with one of the worst clinical outcomes throughout the globe because of its aggressive, metastatic, and drug-resistant nature. During the past decade, several studies have shown that oral, gut, and tumor microbiota play a critical role in the modulation of metabolism and immune responses. Growing pieces of evidence have proved beyond a doubt that the microbiota has a unique ability to influence the tumor microenvironment as well as the metabolism of chemotherapeutic agents or drugs. Given this, microbiota, known as the ecological community of microorganisms, stands to be an avenue of quality research. In this review, we provide detailed and critical information on the role of oral, gut, and pancreatic microbiota disruptions in the development of pancreatic carcinoma. Moreover, we comprehensively discuss the different types of microbiota, their potential role, and mechanism associated with pancreatic carcinoma. The microbiome provides the unique opportunity to enhance the effectiveness of chemotherapeutic agents and immunotherapies for pancreatic cancer by maintaining the right type of microbiota and holds a promising future to enhance the clinical outcomes of patients with pancreatic carcinoma.}, }
@article {pmid34051218, year = {2021}, author = {Wang, H and Banerjee, N and Liang, Y and Wang, G and Hoffman, KL and Khan, MF}, title = {Gut microbiome-host interactions in driving environmental pollutant trichloroethene-mediated autoimmunity.}, journal = {Toxicology and applied pharmacology}, volume = {424}, number = {}, pages = {115597}, pmid = {34051218}, issn = {1096-0333}, support = {R01 ES016302/ES/NIEHS NIH HHS/United States ; R01 ES026887/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Autoimmunity/*drug effects ; Bacteria/*drug effects ; Drug Administration Schedule ; Environmental Pollutants/*toxicity ; Female ; Gastrointestinal Microbiome/*drug effects/physiology ; Inflammation ; Liver/drug effects ; Mice ; Mice, Inbred Strains ; Oxidative Stress ; Spleen/drug effects ; Trichloroethylene/*toxicity ; }, abstract = {Trichloroethene (TCE), a widely used industrial solvent, is associated with the development of autoimmune diseases (ADs), including systemic lupus erythematosus and autoimmune hepatitis. Increasing evidence support a linkage between altered gut microbiome composition and the onset of ADs. However, it is not clear how gut microbiome contributes to TCE-mediated autoimmunity, and initial triggers for microbiome-host interactions leading to systemic autoimmune responses remain unknown. To achieve this, female MRL+/+ mice were treated with 0.5 mg/ml TCE for 52 weeks and fecal samples were subjected to 16S rRNA sequencing to determine the microbiome composition. TCE exposure resulted in distinct bacterial community revealed by β-diversity analysis. Notably, we observed reduction in Lactobacillaceae, Rikenellaceae and Bifidobacteriaceae families, and enrichment of Akkermansiaceae and Lachnospiraceae families after TCE exposure. We also observed significantly increased colonic oxidative stress and inflammatory markers (CD14 and IL-1β), and decreased tight junction proteins (ZO-2, occludin and claudin-3). These changes were associated with increases in serum antinuclear and anti-smooth muscle antibodies and cytokines (IL-6 and IL-12), together with increased PD1 + CD4+ T cells in TCE-exposed spleen and liver tissues. Importantly, fecal microbiota transplantation (FMT) using feces from TCE-treated mice to antibiotics-treated mice induced increased anti-dsDNA antibodies and hepatic CD4+ T cell infiltration in the recipient mice. Our studies thus delineate how imbalance in gut microbiome and mucosal redox status together with gut inflammatory response and permeability changes could be the key factors in contributing to TCE-mediated ADs. Furthermore, FMT studies provide a solid support to a causal role of microbiome in TCE-mediated autoimmunity.}, }
@article {pmid34049374, year = {2021}, author = {Saha, S and Sehgal, K and Singh, S and Grover, M and Pardi, D and Khanna, S}, title = {Postinfection Irritable Bowel Syndrome Following Clostridioides difficile Infection: A Systematic-review and Meta-analysis.}, journal = {Journal of clinical gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MCG.0000000000001536}, pmid = {34049374}, issn = {1539-2031}, abstract = {BACKGROUND: Postinfection irritable bowel syndrome (PI-IBS) affects ~14% patients after acute bacterial enterocolitis.<br><br>AIM: The aim of this study was to conduct a systematic review and meta-analysis to find the prevalence of PI-IBS following Clostridioides difficile infection (CDI).<br><br>METHODS: We systematically searched Medline, Embase, and Web of Science from inception through January 20, 2020 for cohort studies assessing PI-IBS following CDI. Primary outcome was pooled prevalence calculated using inverse variance heterogeneity model [MetaXL (v. 5.3)]. A priori subgroup analyses were done [by irritable bowel syndrome (IBS) diagnostic criteria-Rome vs. others, time of IBS diagnosis-<6 or >6 mo, exclusion or inclusion of pre-existing IBS and CDI treatment-antibiotic with fecal microbiota transplantation vs. antibiotic only]. Heterogeneity was considered substantial if I2>50%.<br><br>RESULTS: From 2007 to 2019, 15 studies were included (10 prospective, 5 retrospective; 9 full-text, 6 abstracts). Data from 1218 patients were included in the quantitative analysis. Risk of bias was low in 7, medium in 4 and high in 4 studies. Pooled prevalence of PI-IBS was 21.1% (95% confidence interval, 8.2%-35.7%), I2=96%. Common PI-IBS subtypes were diarrhea-predominant in 46.3% (50) patients, and mixed in 33.3% (36) patients. Subgroup analyses by IBS diagnostic criteria, time of IBS diagnosis or CDI treatment did not significantly change the primary outcome (all P>0.05), nor decrease heterogeneity. Funnel plot analysis revealed publication bias.<br><br>CONCLUSIONS: Over 20% of patients develop PI-IBS after CDI. Factors such as diagnostic criteria for IBS and CDI treatment did not affect prevalence, though small numbers limit the confidence in these conclusions. Larger, well conducted studies are needed to study PI-IBS in CDI.}, }
@article {pmid34048223, year = {2021}, author = {Liu, J and Zhao, F and Wang, T and Xu, Y and Qiu, J and Qian, Y}, title = {Host Metabolic Disorders Induced by Alterations in Intestinal Flora under Dietary Pesticide Exposure.}, journal = {Journal of agricultural and food chemistry}, volume = {69}, number = {22}, pages = {6303-6317}, doi = {10.1021/acs.jafc.1c00273}, pmid = {34048223}, issn = {1520-5118}, mesh = {Animals ; Dietary Exposure ; *Gastrointestinal Microbiome ; Liver ; Mice ; Obesity ; *Pesticides/toxicity ; }, abstract = {A dietary pesticide residue causes underestimated influences on body health. In this work, experimental mice were exposed to commonly used pesticides that cause insulin resistance, inflammation, and non-alcoholic fatty liver diseases. Alterations in intestinal flora were detected in the exposure groups. The abundance of the flora causing high endotoxin production was intensively increased and led to body inflammation. High Firmicutes/Bacteroidetes and obesity-related flora characteristics were also found. The metabolisms of intestinal flora and host circulation were investigated through metabolomics. The associations of flora with their metabolites and host circulation were also established. Association analysis can determine the influences of pesticide exposure on such a complex system. The affected metabolic pathways in the liver were also determined to clarify the mechanism underlying the effect of pesticide exposure on host physiology. Interventions with fructooligosaccharides and fecal microbiota transplantation alleviated the metabolic disorders, thus directly confirming that the intestinal flora mediates the effects of pesticide exposure on host circulation. This work elucidated the intestinal-flora-mediated effects of dietary pollutant exposure on body health and provided potential measures for regulating flora and host circulation.}, }
@article {pmid34045661, year = {2021}, author = {Qi, R and Sun, J and Qiu, X and Zhang, Y and Wang, J and Wang, Q and Huang, J and Ge, L and Liu, Z}, title = {The intestinal microbiota contributes to the growth and physiological state of muscle tissue in piglets.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {11237}, pmid = {34045661}, issn = {2045-2322}, support = {19513//the Agricultural Development Program of Chongqing/ ; 2018YFD0500404//the National Key R&amp;D Program of China/ ; 2017YFD0500501//the National Key R&amp;D Program of China/ ; 19241//the Financial Resourced Program of Chongqing/ ; }, abstract = {Although the importance of the intestinal microbiota in host growth and health is well known, the relationship between microbiota colonization and muscle development is unclear. In this study, the direct causal effects of the colonization of gut microorganisms on the muscle tissue of piglets were investigated. The body weight and lean mass of germ-free (GF) piglets were approximately 40% lower than those of normal piglets. The deletion of the intestinal microbiota led to weakened muscle function and a reduction in myogenic regulatory proteins, such as MyoG and MyoD, in GF piglets. In addition, the blinded IGF1/AKT/mTOR pathway in GF piglets caused muscle atrophy and autophagy, which were characterized by the high expression of Murf-1 and KLF15. Gut microbiota introduced to GF piglets via fecal microbiota transplantation not only colonized the gut but also partially restored muscle growth and development. Furthermore, the proportion of slow-twitch muscle fibers was lower in the muscle of GF piglets, which was caused by the reduced short-chain fatty acid content in the circulation and impaired mitochondrial function in muscle. Collectively, these findings suggest that the growth, development and function of skeletal muscle in animals are mediated by the intestinal microbiota.}, }
@article {pmid34044101, year = {2021}, author = {Gonzales-Luna, AJ and Spinler, JK and Oezguen, N and Khan, MAW and Danhof, HA and Endres, BT and Alam, MJ and Begum, K and Lancaster, C and Costa, GP and Savidge, TC and Hurdle, JG and Britton, R and Garey, KW}, title = {Systems biology evaluation of refractory Clostridioides difficile infection including multiple failures of fecal microbiota transplantation.}, journal = {Anaerobe}, volume = {70}, number = {}, pages = {102387}, doi = {10.1016/j.anaerobe.2021.102387}, pmid = {34044101}, issn = {1095-8274}, support = {U01 AI124290/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) aims to cure Clostridioides difficile infection (CDI) through reestablishing a healthy microbiome and restoring colonization resistance. Although often effective after one infusion, patients with continued microbiome disruptions may require multiple FMTs. In this N-of-1 study, we use a systems biology approach to evaluate CDI in a patient receiving chronic suppressive antibiotics with four failed FMTs over two years.<br><br>METHODS: Seven stool samples were obtained between 2016-18 while the patient underwent five FMTs. Stool samples were cultured for C. difficile and underwent microbial characterization and functional gene analysis using shotgun metagenomics. C. difficile isolates were characterized through ribotyping, whole genome sequencing, metabolic pathway analysis, and minimum inhibitory concentration (MIC) determinations.<br><br>RESULTS: Growing ten strains from each sample, the index and first four recurrent cultures were single strain ribotype F078-126, the fifth was a mixed culture of ribotypes F002 and F054, and the final culture was ribotype F002. One single nucleotide polymorphism (SNP) variant was identified in the RNA polymerase (RNAP) β-subunit RpoB in the final isolated F078-126 strain when compared to previous F078-126 isolates. This SNV was associated with metabolic shifts but phenotypic differences in fidaxomicin MIC were not observed. Microbiome differences were observed over time during vancomycin therapy and after failed FMTs.<br><br>CONCLUSION: This study highlights the importance of antimicrobial stewardship in patients receiving FMT. Continued antibiotics play a destructive role on a transplanted microbiome and applies selection pressure for resistance to the few antibiotics available to treat CDI.}, }
@article {pmid34035760, year = {2021}, author = {Allegretti, JR}, title = {Update on Fecal Microbiota Transplantation for the Treatment of Inflammatory Bowel Disease.}, journal = {Gastroenterology &amp; hepatology}, volume = {17}, number = {1}, pages = {31-34}, pmid = {34035760}, issn = {1554-7914}, }
@article {pmid34035290, year = {2021}, author = {Malard, F and Vekhoff, A and Lapusan, S and Isnard, F and D'incan-Corda, E and Rey, J and Saillard, C and Thomas, X and Ducastelle-Lepretre, S and Paubelle, E and Larcher, MV and Rocher, C and Recher, C and Tavitian, S and Bertoli, S and Michallet, AS and Gilis, L and Peterlin, P and Chevallier, P and Nguyen, S and Plantamura, E and Boucinha, L and Gasc, C and Michallet, M and Dore, J and Legrand, O and Mohty, M}, title = {Gut microbiota diversity after autologous fecal microbiota transfer in acute myeloid leukemia patients.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {3084}, pmid = {34035290}, issn = {2041-1723}, mesh = {Acute Disease ; Adult ; Aged ; Anti-Bacterial Agents/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Bacteria/classification/drug effects/genetics ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects/genetics ; Humans ; Leukemia, Myeloid/*drug therapy/microbiology ; Male ; Middle Aged ; Prospective Studies ; Transplantation, Autologous ; Treatment Outcome ; Young Adult ; }, abstract = {Acute myeloid leukemia (AML) intensive chemotherapy combined with broad-spectrum antibiotics, leads to gut microbiota dysbiosis promoting pathological conditions and an increased incidence of complications. Here we report findings from a phase II single-arm, multicenter study evaluating autologous fecal microbiota transfer (AFMT) in 25 AML patients treated with intensive chemotherapy and antibiotics (ClinicalTrials.gov number: NCT02928523). The co-primary outcomes of the study are to evaluate the efficacy of AFMT in dysbiosis correction and multidrug-resistant bacteria eradication. The main secondary outcomes are to define a dysbiosis biosignature, to evaluate the effect of dysbiosis correction on patient clinical status, to assess the short and mid-term safety of AFMT in this immunocompromised population, and to evaluate the feasibility of the AFMT procedure and acceptability by the patient. Intensive induction chemotherapy induces a dramatic decrease of α-diversity indices, and a microbial dysbiosis with a significant shift of the microbial communities and domination of pro-inflammatory families. After AFMT treatment, α-diversity indices return to their initial mean levels and the similarity index shows the restoration of microbial communities. The trial meets pre-specified endpoints. AFMT appears to be safe and may be effective for gut microbiota restoration in AML patients receiving intensive chemotherapy and antibiotics, with an excellent gut microbiota reconstruction based on both richness and diversity indices at the species level.}, }
@article {pmid34030988, year = {2021}, author = {Ianiro, G and Porcari, S and Bibbò, S and Giambò, F and Quaranta, G and Masucci, L and Sanguinetti, M and Gasbarrini, A and Cammarota, G}, title = {Donor program for fecal microbiota transplantation: A 3-year experience of a large-volume Italian stool bank.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.dld.2021.04.009}, pmid = {34030988}, issn = {1878-3562}, abstract = {BACKGROUND: Due to the increasing rise of C. difficile infection, stool banks and donor programs have been launched to grant access to fecal microbiota transplantation (FMT). Our aim is to describe characteristics and outcomes of the donor program at our stool bank.<br><br>METHODS: Donor candidates underwent a four-step selection process, including a clinical interview, blood and stool testing, a further questionnaire and a direct stool testing the day of each donation. From March 2020, specific changes to this process were introduced to avoid the potential transmission of COVID-19. We evaluated the rate of excluded candidates at each step of the screening, as well as the number of total fecal aliquots provided by qualified donors.<br><br>RESULTS: Overall, 114 donor candidates were evaluated. Seventy-five candidates declined to join the program for logistic or personal issues, three were excluded after the questionnaire and seven for positive stool exams. Finally, 29 (25%) subjects qualified as stool donors, and provided 70 stool samples. Fifteen samples were excluded after direct molecular stool testing. A total of 127 aliquots was finally obtained.<br><br>CONCLUSIONS: Donor recruitment for FMT is a challenging process, and only a small rate of candidates are eligible as donors.}, }
@article {pmid34030388, year = {2021}, author = {Cheng, W and Wang, Z and Xiong, Y and Wu, Z and Tan, X and Yang, Y and Zhang, H and Zhu, X and Wei, H and Tao, S}, title = {N-(3-oxododecanoyl)-homoserine lactone disrupts intestinal barrier and induces systemic inflammation through perturbing gut microbiome in mice.}, journal = {The Science of the total environment}, volume = {778}, number = {}, pages = {146347}, doi = {10.1016/j.scitotenv.2021.146347}, pmid = {34030388}, issn = {1879-1026}, mesh = {4-Butyrolactone/analogs &amp; derivatives ; Animals ; *Gastrointestinal Microbiome ; Homoserine/analogs &amp; derivatives ; Inflammation ; Mice ; Quorum Sensing ; }, abstract = {As a quorum sensing signal molecule, N-(3-oxododecanoyl)-homoserine lactone (3OC12) regulate the population behavior of microorganisms. Many studies have proved that 3OC12 harm the physiological function of host intestinal epithelial cells. However, the detrimental effects of 3OC12 on intestinal health need verification in animals. Besides, the role of gut microbiome in 3OC12-induced intestinal damage also needs further understanding. In our study, 3OC12 was first administered to specific pathogen-free (SPF) mice, then the fecal microbiome of SPF mice was transplanted into germ-free (GF) mice to reveal the effects of 3OC12 on intestinal health and regulatory mechanisms of the intestinal microbiome. 3OC12 treatment significantly decreased body weight, shortened colonic length, disrupted the morphology of the colonic epithelium and increased the histopathological score of the colon in SPF mice. The levels of diamine peroxidase, d-lactate, TNF-α, IL-1β, and IL-8 were found to be significantly elevated in the serum of 3OC12 mice, while the levels of IL-10 were significantly reduced. Besides, the fecal microbial community of mice was also altered in the 3OC12-treated SPF mice. The results of fecal microbial transplantation (FMT) experiment showed that the phenotypes in SPF mice were almost reproduced in GF mice, manifested by body weight loss, colon damage and changed in serum chemical markers. More importantly, a joint analysis of fecal microbes in SPF and GF mice revealed Feature14_Elizabethkingia spp. was common differential bacteria in the feces of two kinds of mice treated with and without FMT. Our results demonstrated that 3OC12 challenge led to systemic inflammation and body weight loss in mice by disrupting intestinal barrier function, in which gut microbiome played a key role. These findings increased our understanding of the mechanism of intestinal injury caused by 3CO12, providing new ideas for the prevention and therapy of diseases caused by bacterial infection from the perspective of intestinal microbiome.}, }
@article {pmid34030162, year = {2021}, author = {Lemos, MPC and Zucoloto, TG and Oliveira, MC and de Oliveira, GLV}, title = {Dysbiosis and Gut Microbiota Modulation in Systemic Sclerosis.}, journal = {Journal of clinical rheumatology : practical reports on rheumatic &amp; musculoskeletal diseases}, volume = {}, number = {}, pages = {}, doi = {10.1097/RHU.0000000000001748}, pmid = {34030162}, issn = {1536-7355}, abstract = {ABSTRACT: Gastrointestinal (GI) involvement is an early manifestation in systemic sclerosis (SSc), affecting more than 90% of patients, and severe GI disease is a marker of poor prognosis and mortality. Recent studies have hypothesized that alterations of the intestinal microbiota, known as dysbiosis, may represent 1 of the possible environmental factors influencing SSc disease status. In addition, specific microorganisms may be associated with SSc pathogenesis, progression, and GI manifestations. Therapeutic approaches aiming to modulate the intestinal microbiota have emerged, as alternatives to treat GI symptoms, and dietary interventions, probiotic administration, and fecal microbiota transplantation are potential therapies for SSc patients. However, given the complexity and variability of pathogenesis and clinical manifestations in SSc, these therapies need to be combined with additional interventions that target other disease components. Here, we summarize studies addressing intestinal dysbiosis in SSc and discuss the potential of microbiota modulators to treat SSc-related GI disorders.}, }
@article {pmid34029686, year = {2021}, author = {Payne, E and Harrington, K and Richard, P and Brackin, R and Davis, R and Couture, S and Liff, J and Asmus, F and Mutina, E and Fisher, A and Giuvelis, D and Sannajust, S and Rostama, B and King, T and Mattei, LM and Lee, JJ and Friedman, ES and Bittinger, K and May, M and Stevenson, GW}, title = {Effects of Vancomycin on Persistent Pain-Stimulated and Pain-Depressed Behaviors in Female Fischer Rats With or Without Voluntary Access to Running Wheels.}, journal = {The journal of pain}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jpain.2021.05.003}, pmid = {34029686}, issn = {1528-8447}, abstract = {The present experiments determined the effects of the narrow-spectrum antibiotic vancomycin on inflammatory pain-stimulated and pain-depressed behaviors in rats. Persistent inflammatory pain was modeled using dilute formalin (0.5%). Two weeks of oral vancomycin administered in drinking water attenuated Phase II formalin pain-stimulated behavior, and prevented formalin pain-depressed wheel running. Fecal microbiota transplantation produced a non-significant trend toward reversal of the vancomycin effect on pain-stimulated behavior. Vancomycin depleted Firmicutes and Bacteroidetes populations in the gut while having a partial sparing effect on Lactobacillus species and Clostridiales. The vancomycin treatment effect was associated with an altered profile in amino acid concentrations in the gut with increases in arginine, glycine, alanine, proline, valine, leucine, and decreases in tyrosine and methionine. These results indicate that vancomycin may have therapeutic effects against persistent inflammatory pain conditions that are distal to the gut. Perspective: The narrow-spectrum antibiotic vancomycin reduces pain-related behaviors in the formalin model of inflammatory pain. These data suggest that manipulation of the gut microbiome may be one method to attenuate inflammatory pain amplitude.}, }
@article {pmid34025607, year = {2021}, author = {Yu, X and Zhou, G and Shao, B and Zhou, H and Xu, C and Yan, F and Wang, L and Chen, G and Li, J and Fu, X}, title = {Gut Microbiota Dysbiosis Induced by Intracerebral Hemorrhage Aggravates Neuroinflammation in Mice.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {647304}, pmid = {34025607}, issn = {1664-302X}, abstract = {Intracerebral hemorrhage (ICH) induces a strong hematoma-related neuroinflammatory reaction and alters peripheral immune homeostasis. Recent research has found that gut microbiota plays a role in neurodegeneration and autoimmune diseases by regulating immune homeostasis and neuroinflammation. Therefore, we investigated the relationship between ICH, microbiota alteration, and immune responses after hematoma-induced acute brain injury. In our study, we used a mouse model of ICH, and 16S ribosomal RNA sequencing showed that ICH causes gut microbiota dysbiosis, which in turn affects ICH outcome through immune-mediated mechanisms. There was prominent reduced species diversity and microbiota overgrowth in the dysbiosis induced by ICH, which may reduce intestinal motility and increase gut permeability. In addition, recolonizing ICH mice with a normal health microbiota ameliorates functional deficits and neuroinflammation after ICH. Meanwhile, cell-tracking studies have demonstrated the migration of intestinal lymphocytes to the brain after ICH. In addition, therapeutic transplantation of fecal microbiota improves intestinal barrier damage. These results support the conclusion that the gut microbiome is a target of ICH-induced systemic alteration and is considered to have a substantial impact on ICH outcome.}, }
@article {pmid34025075, year = {2021}, author = {El-Salhy, M and Casen, C and Valeur, J and Hausken, T and Hatlebakk, JG}, title = {Responses to faecal microbiota transplantation in female and male patients with irritable bowel syndrome.}, journal = {World journal of gastroenterology}, volume = {27}, number = {18}, pages = {2219-2237}, pmid = {34025075}, issn = {2219-2840}, mesh = {Europe ; Fecal Microbiota Transplantation/adverse effects ; Feces ; Female ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome/diagnosis/therapy ; Male ; Quality of Life ; RNA, Ribosomal, 16S ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) seems to be a promising treatment for irritable bowel syndrome (IBS) patients. In Western countries (United States and Europe), there is a female predominance in IBS. A sex difference in the response to FMT has been reported recently in IBS patients.<br><br>AIM: To investigate whether there was a sex difference in the response to FMT in the IBS patients who were included in our previous randomized controlled trial of the efficacy of FMT.<br><br>METHODS: The study included 164 IBS patients who participated in our previous randomized controlled trial. These patients had moderate-to-severe IBS symptoms belonging to the IBS-D (diarrhoea-predominant), IBS-C (constipation-predominant) and IBS-M (mixed) subtypes, and had not responded to the National Institute for Health and Care Excellence (NICE)-modified diet. They belonged in three groups: placebo (own faeces), and active treated group (30-g or 60-g superdonor faeces). The patients completed the IBS severity scoring system (IBS-SSS), Fatigue Assessment Scale (FAS) and the IBS quality of life scale (IBS-QoL) questionnaires at the baseline and 2 wk, 1 mo and 3 mo after FMT. They also provided faecal samples at the baseline and 1 mo after FMT. The faecal bacteria profile and dysbiosis were determined using the 16S rRNA gene polymerase chain reaction DNA amplification covering V3-V9; probe labelling by single nucleotide extension and signal detection. The levels of short-chain fatty acids (SCFAs) were determined by gas chromatography and flame ionization.<br><br>RESULTS: There was no sex difference in the response to FMT either in the placebo group or active treated group. There was no difference between females and males in either the placebo group or actively treated groups in the total score on the IBS-SSS, FAS or IBS-QoL, in dysbiosis, or in the faecal bacteria or SCFA level. However, the response rate was significantly higher in females with diarrhoea-predominant (IBS-D) than that of males at 1 mo, and 3 mo after FMT. Moreover, IBS-SSS total score was significantly lower in female patients with IBS-D than that of male patients both 1 mo and 3 mo after FMT.<br><br>CONCLUSION: There was no sex difference in the response to FMT among IBS patients with moderate-to-severe symptoms who had previously not responded to NICE-modified diet. However, female patients with IBS-D respond better and have higher reduction of symptoms than males after FMT.}, }
@article {pmid34020027, year = {2021}, author = {Saeed, M and Shoaib, A and Kandimalla, R and Javed, S and Almatroudi, A and Gupta, R and Aqil, F}, title = {Microbe-based therapies for colorectal cancer: Advantages and limitations.}, journal = {Seminars in cancer biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.semcancer.2021.05.018}, pmid = {34020027}, issn = {1096-3650}, abstract = {Cancer is one of the leading global causes of death in both men and women. Colorectal cancer (CRC) alone accounts for ∼10 % of total new global cases and poses an over 4% lifetime risk of developing cancer. Recent advancements in the field of biotechnology and microbiology concocted novel microbe-based therapies to treat various cancers, including CRC. Microbes have been explored for human use since centuries, especially for the treatment of various ailments. The utility of microbes in cancer therapeutics is widely explored, and various bacteria, fungi, and viruses are currently in use for the development of cancer therapeutics. The human gut hosts about 100 trillion microbes that release their metabolites in active, inactive, or dead conditions. Microbial secondary metabolites, proteins, immunotoxins, and enzymes are used to target cancer cells to induce cell cycle arrest, apoptosis, and death. Various approaches, such as dietary interventions, the use of prebiotics and probiotics, and fecal microbiota transplantation have been used to modulate the gut microbiota in order to prevent or treat CRC pathogenesis. The present review highlights the role of the gut microbiota in CRC precipitation, the potential mechanisms and use of microorganisms as CRC biomarkers, and strategies to modulate microbiota for the prevention and treatment of CRC.}, }
@article {pmid34019628, year = {2021}, author = {Ni, H and Chen, Y and Xia, W and Wang, C and Hu, C and Sun, L and Tang, W and Cui, H and Shen, T and Liu, Y and Li, J}, title = {SATB2 defect promotes colitis and colitis-associated colorectal cancer by impairing Cl -/HCO3 - exchange and homeostasis of gut microbiota.}, journal = {Journal of Crohn's &amp; colitis}, volume = {}, number = {}, pages = {}, doi = {10.1093/ecco-jcc/jjab094}, pmid = {34019628}, issn = {1876-4479}, abstract = {BACKGROUND: SATB2 is a diagnostic biomarker and a favorable prognostic marker for colorectal cancer (CRC), but its role in colitis and colitis-associated colorectal cancer (CAC) is unknown.<br><br>METHODS: Intestinal epithelial specific Satb2 knockout (Satb2 IEC-KO) and control mice was induced by DSS and AOM. RNA-seq analysis was performed on colonic tissues, and 16S rDNA-Seq on fecal bacterial DNA from Satb2 IEC-KO and control mice. Immunohistochemistry and flow cytometry were performed the reveal the proportion of different immune cells. ChIP and luciferase reporter were applied to show the regulatory role of SATB2 on SLC26A3, of which the Cl -/HCO3 - exchange activity was measured fluorometrically by the pHi-sensitive dye. Bacteroides was detected by FISH on colonic tissue.<br><br>RESULTS: Satb2 IEC-KO mice suffered from intestinal epithelial damage spontaneously, and developed more severe colitis and CAC. The expression of SLC26A3 correlated well with SATB2 revealed by RNA-seq and TCGA data, and was governed by SATB2 confirmed by ChIP and luciferase reporter experiments. Decreased intestinal flora diversity was seen in Satb2 IEC-KO mice. Bacteroides were more abundant and could colonize into the inner layer of colonic mucosa in Satb2 IEC-KO mice. Fecal microbiome transplantation from Satb2 IEC-KO mice aggregated colitis and M1 macrophages infiltration.<br><br>CONCLUSION: SATB2 plays a vital role in maintaining intestinal homeostasis and its deficiency promotes the development of colitis and CAC by influencing the intestinal luminal environment and gut flora.}, }
@article {pmid34018696, year = {2021}, author = {Lu, C and Tang, S and Han, J and Fan, S and Huang, Y and Zhang, Z and Zhou, J and Ming, T and Li, Y and Su, X}, title = {Apostichopus japonicus Oligopeptide Induced Heterogeneity in the Gastrointestinal Tract Microbiota and Alleviated Hyperuricemia in a Microbiota-Dependent Manner.}, journal = {Molecular nutrition &amp; food research}, volume = {65}, number = {14}, pages = {e2100147}, doi = {10.1002/mnfr.202100147}, pmid = {34018696}, issn = {1613-4133}, abstract = {SCOPE: This study aims to investigate the protective effect of Apostichopus japonicus oligopeptide (AJOP) on hyperuricemia, demonstrate the modulation of the gastrointestinal tract (GIT) microbiota, and clarify the underlying microbiota-dependent mechanism.<br><br>METHODS AND RESULTS: Hyperuricemic mice treated with AJOP and subjected to corresponding fecal microbiota transplantation (FMT) are used to observe the beneficial effects of AJOP and microbiota. Gene transcriptions are measured using quantitative real-time PCR. The GIT (stomach, colon, cecum, and feces) microbiota is analyzed by 16S rDNA sequencing and the short-chain fatty acids are detected using GC-MS. Dietary administration of AJOP significantly alleviates hyperuricemia, regulates uric acid metabolism, inhibites the activation of the NLRP3 inflammasome and NF-κB-related signaling pathway, and restores m6A methylation levels. In addition, substantial heterogeneity is observed in GIT microbiota. Furthermore, FMT effectively alleviates hyperuricemia in mice by selectively regulating the corresponding pathways associated with AJOP treatment, indicating that the mechanism underlying the protective effects of AJOP is partly microbiota-dependent.<br><br>CONCLUSION: This study demonstrates that AJOP exerts a protective effect on hyperuricemic mice by regulating uric acid metabolism, resulting in substantial heterogeneity among the GIT microbiota, thus mediating the beneficial effects in a microbiota-dependent manner.}, }
@article {pmid34017186, year = {2021}, author = {Wang, J and Li, X and Wu, X and Wang, Z and Wu, X and Wang, S and Jing, G and Yan, T}, title = {Fecal Microbiota Transplantation as an Effective Treatment for Carbapenem-Resistant Klebsiella pneumoniae Infection in a Renal Transplant Patient.}, journal = {Infection and drug resistance}, volume = {14}, number = {}, pages = {1805-1811}, pmid = {34017186}, issn = {1178-6973}, abstract = {Background: In renal transplant recipients, carbapenem-resistant Klebsiella pneumoniae (CRKP) infection is a common complication, and usually associated with severe clinical outcomes due to a lack of effective treatment.<br><br>Case Presentation: A 37-year-old woman with CRKP infection one month after kidney transplantation was involved in this study. Microbial characteristics of fecal samples from the patient were analyzed. Fecal microbiota transplantation (FMT) was performed for treating the CRKP infection. One week after FMT, the patient's urine and anal swab cultures returned negative for CRKP, and 17 days after FMT, the incision showed complete healing. Moreover, the patient had no symptoms of infection two months after FMT. Alpha diversity analyses showed that before FMT, the patient was associated with obviously lower species richness and diversity than the donor, which significantly increased at one week, three weeks and two months after FMT. Beta diversity analyses showed that though the patient's microbial community post-FMT still differed from the donor composition, their distances decreased visibly, especially at one week and three weeks after FMT. Obvious shift in microbial composition could be observed before and after FMT. The microbial composition of the patient post FMT resembled the donor composition. Relative abundance of genera such as Phascolarctobacterium and Lachnoclostridium increased after FMT, while the relative abundance of Klebsiella significantly decreased.<br><br>Conclusion: This study demonstrated the therapeutic effect of FMT on infections caused by CRKP for a renal transplant patient. Further studies are required to confirm the findings of this study.}, }
@article {pmid34017060, year = {2021}, author = {Kim, JH and Kim, K and Kim, W}, title = {Gut microbiota restoration through fecal microbiota transplantation: a new atopic dermatitis therapy.}, journal = {Experimental &amp; molecular medicine}, volume = {53}, number = {5}, pages = {907-916}, pmid = {34017060}, issn = {2092-6413}, support = {NRF-2019R1A6A3A01093804//National Research Foundation of Korea (NRF)/ ; }, abstract = {The pathogenesis of atopic dermatitis (AD) involves complex factors, including gut microbiota and immune modulation, which remain poorly understood. The aim of this study was to restore gut microbiota via fecal microbiota transplantation (FMT) to ameliorate AD in mice. FMT was performed using stool from donor mice. The gut microbiota was characterized via 16S rRNA sequencing and analyzed using Quantitative Insights into Microbial Ecology 2 with the DADA2 plugin. Gut metabolite levels were determined by measuring fecal short-chain fatty acid (SCFA) contents. AD-induced allergic responses were evaluated by analyzing blood parameters (IgE levels and eosinophil percentage, eosinophil count, basophil percentage, and monocyte percentage), the levels of Th1 and Th2 cytokines, dermatitis score, and the number of mast cells in the ileum and skin tissues. Calprotectin level was measured to assess gut inflammation after FMT. FMT resulted in the restoration of gut microbiota to the donor state and increases in the levels of SCFAs as gut metabolites. In addition, FMT restored the Th1/Th2 balance, modulated Tregs through gut microbiota, and reduced IgE levels and the numbers of mast cells, eosinophils, and basophils. FMT is associated with restoration of gut microbiota and immunologic balance (Th1/Th2) along with suppression of AD-induced allergic responses and is thus a potential new therapy for AD.}, }
@article {pmid34016163, year = {2021}, author = {Lei, Y and Tang, L and Liu, S and Hu, S and Wu, L and Liu, Y and Yang, M and Huang, S and Tang, X and Tang, T and Zhao, X and Vlodavsky, I and Zeng, S and Tang, B and Yang, S}, title = {Parabacteroides produces acetate to alleviate heparanase-exacerbated acute pancreatitis through reducing neutrophil infiltration.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {115}, pmid = {34016163}, issn = {2049-2618}, support = {81661148050//National Natural Science Foundation of China/ ; 81972327//National Natural Science Foundation of China/ ; }, mesh = {*Acetates ; Acute Disease ; Animals ; *Bacteroides ; *Gastrointestinal Microbiome ; Glucuronidase ; Mice ; Mice, Transgenic ; *Neutrophil Infiltration ; Pancreatitis/*microbiology ; }, abstract = {BACKGROUND: The endoglycosidase heparanase which degrades heparan sulfate proteoglycans, exerts a pro-inflammatory mediator in various inflammatory disorders. However, the function and underlying mechanism of heparanase in acute pancreatitis remain poorly understood. Here, we investigated the interplay between heparanase and the gut microbiota in the development of acute pancreatitis.<br><br>METHODS: Acute pancreatitis was induced in wild-type and heparanase-transgenic mice by administration of caerulein. The differences in gut microbiota were analyzed by 16S ribosomal RNA sequencing. Antibiotic cocktail experiment, fecal microbiota transplantation, and cohousing experiments were used to assess the role of gut microbiota.<br><br>RESULTS: As compared with wild-type mice, acute pancreatitis was exacerbated in heparanase-transgenic mice. Moreover, the gut microbiota differed between heparanase-transgenic and wild-type mice. Heparanase exacerbated acute pancreatitis in a gut microbiota-dependent manner. Specially, the commensal Parabacteroides contributed most to distinguish the differences between wild-type and heparanase-transgenic mice. Administration of Parabacteroides alleviated acute pancreatitis in wild-type and heparanase-transgenic mice. In addition, Parabacteroides produced acetate to alleviate heparanase-exacerbated acute pancreatitis through reducing neutrophil infiltration.<br><br>CONCLUSIONS: The gut-pancreas axis played an important role in the development of acute pancreatitis and the acetate produced by Parabacteroides may be beneficial for acute pancreatitis treatment. Video abstract.}, }
@article {pmid34015282, year = {2021}, author = {Dixit, K and Chaudhari, D and Dhotre, D and Shouche, Y and Saroj, S}, title = {Restoration of dysbiotic human gut microbiome for homeostasis.}, journal = {Life sciences}, volume = {278}, number = {}, pages = {119622}, doi = {10.1016/j.lfs.2021.119622}, pmid = {34015282}, issn = {1879-0631}, mesh = {Animals ; Dysbiosis/microbiology/*therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Homeostasis ; Humans ; Immunomodulation ; Microbiota ; Prebiotics/administration &amp; dosage ; Probiotics/therapeutic use ; }, abstract = {The human microbiome is a complex and dynamic ecosystem, and the imbalance of its microbial community structure from the normal state is termed dysbiosis. The dysbiotic gut microbiome has been proved to be related to several pathological conditions like Inflammatory Bowel Disease (IBD), Irritable Bowel Syndrome (IBS), Colorectal Cancer (CRC), etc., and several other extra-intestinal conditions like Type 1 &amp; 2 diabetes, obesity, etc. The complex gut microbial ecosystem starts to build before the birth of an individual. It is known to get affected by several factors such as birth mode, individual lifestyle, dietary practices, medications, and antibiotics. A dysbiotic microbiome can potentially hamper host homeostasis due to its role in immune modulation, metabolism, nutrient synthesis, etc. Restoration of the dysbiotic gut microbiome has emerged as a promising aid and a better therapeutic approach. Several approaches have been investigated to achieve this goal, including prebiotics and probiotics, Fecal Microbiota Transplantation (FMT), extracellular vesicles, immune modulation, microbial metabolites, dietary interventions, and phages. This review discusses the various factors that influence the human microbiome with respect to their cause-effect relationship and the effect of gut microbiome compositional changes on the brain through the gut-brain axis. We also discuss the practices used globally for gut microbiome restoration purposes, along with their effectiveness.}, }
@article {pmid34006020, year = {2021}, author = {Kragsnaes, MS and Sødergren, ST and Kjeldsen, J and Horn, HC and Munk, HL and Pedersen, JK and Klinkby, CS and de Wit, M and Ahlmark, NG and Tjørnhøj-Thomsen, T and Ellingsen, T}, title = {Experiences and perceptions of patients with psoriatic arthritis participating in a trial of faecal microbiota transplantation: a nested qualitative study.}, journal = {BMJ open}, volume = {11}, number = {3}, pages = {e039471}, pmid = {34006020}, issn = {2044-6055}, mesh = {*Antirheumatic Agents ; *Arthritis, Psoriatic/therapy ; Double-Blind Method ; Fecal Microbiota Transplantation ; Humans ; Perception ; }, abstract = {OBJECTIVES: Patients' first-hand experiences of faecal microbiota transplantation (FMT) performed in a rheumatological care setting have yet to be elucidated. The objectives were to explore participants' perceptions of being part of an FMT trial thereby identifying potential trial participation effects and enlightening the patient perspective on the outlook for future FMT trials in rheumatic diseases.<br><br>DESIGN: In a qualitative study nested within a double-blind, randomised, placebo-controlled trial (RCT) testing FMT as a potential new antirheumatic treatment, semistructured telephone interviews were conducted following the trial participants' final 26-week visit. Qualitative researchers, who did not take part in the main trial, performed the interviews and the primary analysis. The experiences explored related to the conduct of the RCT and changes in the participants' everyday life. The analysis was carried out using a thematic approach.<br><br>SETTING: A Danish rheumatology university outpatient clinic with nationwide inclusion.<br><br>PARTICIPANTS: The study included 10 patients with psoriatic arthritis (PsA) who were unaware of their treatment allocation (FMT/sham transplantation) and completed the final 26-week trial visit.<br><br>RESULTS: Participation in the RCT influenced the patients' understanding of PsA and induced positive changes in their everyday life. Renewed hopes for the future in addition to a feeling of enhanced care contributed to significant trial participation effects. FMT was deemed a tolerable and safe treatment.<br><br>CONCLUSIONS: Discrepancies between the clinical and the research setting should be considered when discussing the clinical relevance of the results of the RCT. Overall, patients with PsA who have participated in an RCT testing FMT find the treatment acceptable and safe encouraging more research into the field of microbiota-targeted interventions in rheumatic diseases.<br><br>TRIAL REGISTRATION NUMBER: NCT03058900; Pre-results.}, }
@article {pmid34004414, year = {2021}, author = {Feng, D and Chen, B and Zeng, B and Xiao, L and Yan, J and Yang, T and Zhu, J and Li, T and Wang, L and Wei, H and Chen, J}, title = {Fecal microbiota from children with vitamin A deficiency impair colonic barrier function in germ-free mice: The possible role of alterative bile acid metabolites.}, journal = {Nutrition (Burbank, Los Angeles County, Calif.)}, volume = {90}, number = {}, pages = {111274}, doi = {10.1016/j.nut.2021.111274}, pmid = {34004414}, issn = {1873-1244}, abstract = {OBJECTIVE: This study explores the effects of fecal microbiota from children with vitamin A (VA) deficiency on colonic mucosal barrier function.<br><br>METHODS: The composition of gut microbes was identified in children with different VA levels, then feces from children with normal VA or VA deficiency was collected separately and transplanted into germ-free (GF) mice, respectively. Three weeks after transplantation, the colon morphology, colonic tight junction proteins, gut microbes, and metabolites were evaluated.<br><br>RESULTS: In children, Bifidobacterium and Bacteroides were positively correlated with VA levels. Colonization of VA deficiency fecal microbiota markedly impaired colonic development in GF mice, down-regulated colonic tight junction-related proteins occludin and claudin-1, and reduced immunoglobulin A secretion. Furthermore, fecal microbiota transplantation with different VA levels altered composition of gut microbes and bile acid metabolism pathways in GF mice.<br><br>CONCLUSION: These data suggest that fecal microbiota from children with VA deficiency attenuates colonic barrier function in GF mice, which may be achieved by changing the bile acid metabolic pathways.}, }
@article {pmid34003771, year = {2021}, author = {Sharma, D}, title = {Towards Taming the Bugs to Improve the Drugs for Breast Cancer.}, journal = {Cancer research}, volume = {81}, number = {8}, pages = {1937-1939}, doi = {10.1158/0008-5472.CAN-21-0300}, pmid = {34003771}, issn = {1538-7445}, abstract = {The identification of microbial networks that are predictive of disease progression and response to therapy will not only increase our understanding of the connection between microbiota and breast cancer, but also pave the way for the development of novel microbiota-based therapeutic interventions. The study by Di Modica and colleagues points to the existence of specific microbiota in patients with HER2+ breast cancer that can influence their response to trastuzumab. This information can potentially be used to develop novel therapeutic regimens combining fecal microbiota transplant with standard cancer therapy.See related article by Di Modica et al., p. 2195.}, }
@article {pmid34003768, year = {2021}, author = {Baruch, EN and Wang, J and Wargo, JA}, title = {Gut Microbiota and Antitumor Immunity: Potential Mechanisms for Clinical Effect.}, journal = {Cancer immunology research}, volume = {9}, number = {4}, pages = {365-370}, doi = {10.1158/2326-6066.CIR-20-0877}, pmid = {34003768}, issn = {2326-6074}, support = {R01 CA219896/CA/NCI NIH HHS/United States ; }, abstract = {Several landmark preclinical studies have shown an association between the gut microbiota and the effectiveness of immunotherapy for cancer. These studies have sparked clinical trials aimed at modulating the gut microbiota in order to improve clinical response rates to immunotherapy. Despite this, the mechanisms through which the gut microbiota influences the effectiveness of immunotherapy are still incompletely characterized. Preclinical and preliminary clinical findings from numerous types of gut microbiota modulation studies, including fecal transplantation, probiotics, consortia, and diet, demonstrate that favorable microbiota modulation is associated with increased intratumoral infiltration of CD8+ effector T cells. This CD8+ T-cell infiltration is often associated with enhanced intratumoral activity of T-helper type 1 cells and dendritic cells and a lower density of immunosuppressive cells. Herein, we discuss how gut microbiota may affect the activity of immune cells by at least three interlacing mechanisms: activation of pattern recognition receptors, molecular mimicry, and impact of metabolites. We also discuss the therapeutic potential and limitations of the different gut microbiota modulation techniques and their putative mechanisms of immune activation.}, }
@article {pmid33996366, year = {2021}, author = {Niina, A and Kibe, R and Suzuki, R and Yuchi, Y and Teshima, T and Matsumoto, H and Kataoka, Y and Koyama, H}, title = {Fecal microbiota transplantation as a new treatment for canine inflammatory bowel disease.}, journal = {Bioscience of microbiota, food and health}, volume = {40}, number = {2}, pages = {98-104}, pmid = {33996366}, issn = {2186-6953}, abstract = {In human medicine, fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infection. It has also been tested as a treatment for multiple gastrointestinal diseases, including inflammatory bowel disease (IBD). However, only a few studies have focused on the changes in the microbiome following FMT for canine IBD. Here, we performed FMT in nine dogs with IBD using the fecal matter of healthy dogs and investigated the subsequent changes in the fecal microbiome and clinical signs. In three dogs, the fecal microbiome was examined by 16S rRNA sequencing. Fusobacteria were observed at a low proportion in dogs with IBD. However, the post-FMT microbiome became diverse and showed a significant increase in Fusobacteria proportion. Fusobacterium was detected in the nine dogs by quantitative polymerase chain reaction. The proportion of Fusobacterium in the post-FMT fecal microbiome was significantly increased (p<0.05). The changes in clinical signs (e.g., vomiting, diarrhea, and weight loss) were evaluated according to the canine inflammatory bowel disease activity index. The score of this index significantly decreased in all dogs (p<0.05) with improvements in clinical signs. These improvements were related to the changes in the proportion of microbes, particularly the increase in Fusobacterium. The dogs with IBD showed a lower proportion of Fusobacterium than healthy dogs. This suggests that a low proportion of Fusobacterium is a characteristic feature of canine IBD and that Fusobacterium is involved in this disease. The results of this study may help elucidate the pathogenesis of this disease and its association with Fusobacterium.}, }
@article {pmid33995583, year = {2021}, author = {Chaar, A and Feuerstadt, P}, title = {Evolution of clinical guidelines for antimicrobial management of Clostridioides difficile infection.}, journal = {Therapeutic advances in gastroenterology}, volume = {14}, number = {}, pages = {17562848211011953}, pmid = {33995583}, issn = {1756-283X}, abstract = {Clostridioides difficile infection (CDI) has been an epidemic for many years. Our biggest challenge in treating CDI is preventing recurrence, which is seen in approximately 25% of patients with initial infection and in 40-60% of those with subsequent episodes. Given the major disease burden of this infection, appropriate data-driven treatment remains essential. Clinical treatment guidelines provide an unbiased critical analysis of the literature, integrating the quality of the available data to make recommendations. As CDI has been evolving and more research has become available, the frequency of guideline issue from various global societies has increased, as has the detail of the recommendations to fit more relevant clinical scenarios. In this review, we will discuss clinical guideline recommendations over three time periods: The Initial Guidelines 1995-1997, The Second Wave 2009-2013, and The Modern Era 2014-present. We see the changing recommendations from metronidazole or vancomycin for initial infection during earlier times to preferential treatment with fidaxomicin within the Infectious Diseases Society of America (IDSA) and Society of Healthcare Epidemiology of America (SHEA) joint guidelines provisional update in late 2020. The recommended treatments for first recurrence were initially with the same antimicrobial as the first episode but have since changed to having multiple options for one or more recurrences. We have also seen the addition of immune boosting treatments, including fecal microbiota transplantation (FMT)/microbiota restoration therapy (MRT) and bezlotoxumab in the more modern recommendations. As the guidelines are evolving with the times, it remains important to understand the differences among them so we can apply this information clinically and optimize patient outcomes.}, }
@article {pmid33994854, year = {2021}, author = {Yu, M and Alimujiang, M and Hu, L and Liu, F and Bao, Y and Yin, J}, title = {Berberine alleviates lipid metabolism disorders via inhibition of mitochondrial complex I in gut and liver.}, journal = {International journal of biological sciences}, volume = {17}, number = {7}, pages = {1693-1707}, pmid = {33994854}, issn = {1449-2288}, abstract = {This study is to investigate the relationship between berberine (BBR) and mitochondrial complex I in lipid metabolism. BBR reversed high-fat diet-induced obesity, hepatic steatosis, hyperlipidemia and insulin resistance in mice. Fatty acid consumption, β-oxidation and lipogenesis were attenuated in liver after BBR treatment which may be through reduction in SCD1, FABP1, CD36 and CPT1A. BBR promoted fecal lipid excretion, which may result from the reduction in intestinal CD36 and SCD1. Moreover, BBR inhibited mitochondrial complex I-dependent oxygen consumption and ATP synthesis of liver and gut, but no impact on activities of complex II, III and IV. BBR ameliorated mitochondrial swelling, facilitated mitochondrial fusion, and reduced mtDNA and citrate synthase activity. BBR decreased the abundance and diversity of gut microbiome. However, no change in metabolism of recipient mice was observed after fecal microbiota transplantation from BBR treated mice. In primary hepatocytes, BBR and AMPK activator A769662 normalized oleic acid-induced lipid deposition. Although both the agents activated AMPK, BBR decreased oxygen consumption whereas A769662 increased it. Collectively, these findings indicated that BBR repressed complex I in gut and liver and consequently inhibited lipid metabolism which led to alleviation of obesity and fatty liver. This process was independent of intestinal bacteria.}, }
@article {pmid33989072, year = {2021}, author = {Bonde, A and Daly, S and Kirsten, J and Kondapaneni, S and Mellnick, V and Menias, CO and Katabathina, VS}, title = {Human Gut Microbiota-associated Gastrointestinal Malignancies: A Comprehensive Review.}, journal = {Radiographics : a review publication of the Radiological Society of North America, Inc}, volume = {41}, number = {4}, pages = {1103-1122}, doi = {10.1148/rg.2021200168}, pmid = {33989072}, issn = {1527-1323}, abstract = {The human gastrointestinal tract houses trillions of microbes. The gut and various types of microorganisms, including bacteria, viruses, fungi, and archaea, form a complex ecosystem known as the gut microbiota, and the whole genome of the gut microbiota is referred to as the gut microbiome. The gut microbiota is essential for homeostasis and the overall well-being of a person and is increasingly considered an adjunct "virtual organ," with a complexity level comparable to that of the other organ systems. The gut microbiota plays an essential role in nutrition, local mucosal homeostasis, inflammation, and the mucosal immune system. An imbalanced state of the gut microbiota, known as dysbiosis, can predispose to development of various gastrointestinal malignancies through three speculated pathogenic mechanisms: (a) direct cytotoxic effects with damage to the host DNA, (b) disproportionate proinflammatory signaling inducing inflammation, and (c) activation of tumorigenic pathways or suppression of tumor-suppressing pathways. Several microorganisms, including Helicobacter pylori, Epstein-Barr virus, human papillomavirus, Mycoplasma species, Escherichia coli, and Streptococcus bovis, are associated with gastrointestinal malignancies such as esophageal adenocarcinoma, gastric adenocarcinoma, gastric mucosa-associated lymphoid tissue lymphoma, colorectal adenocarcinoma, and anal squamous cell carcinoma. Imaging plays a pivotal role in diagnosis and management of microbiota-associated gastrointestinal malignancies. Appropriate use of probiotics, fecal microbiota transplantation, and overall promotion of the healthy gut are ongoing areas of research for prevention and treatment of malignancies. Online supplemental material is available for this article. ©RSNA, 2021.}, }
@article {pmid33985595, year = {2021}, author = {Wilson, BC and Vatanen, T and Jayasinghe, TN and Leong, KSW and Derraik, JGB and Albert, BB and Chiavaroli, V and Svirskis, DM and Beck, KL and Conlon, CA and Jiang, Y and Schierding, W and Holland, DJ and Cutfield, WS and O'Sullivan, JM}, title = {Strain engraftment competition and functional augmentation in a multi-donor fecal microbiota transplantation trial for obesity.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {107}, pmid = {33985595}, issn = {2049-2618}, mesh = {Adolescent ; Australia ; *Dysbiosis/therapy ; *Fecal Microbiota Transplantation ; Feces ; Female ; Humans ; Male ; Obesity/therapy ; Treatment Outcome ; }, abstract = {BACKGROUND: Donor selection is an important factor influencing the engraftment and efficacy of fecal microbiota transplantation (FMT) for complex conditions associated with microbial dysbiosis. However, the degree, variation, and stability of strain engraftment have not yet been assessed in the context of multiple donors.<br><br>METHODS: We conducted a double-blinded randomized control trial of FMT in 87 adolescents with obesity. Participants were randomized to receive multi-donor FMT (capsules containing the fecal microbiota of four sex-matched lean donors) or placebo (saline capsules). Following a bowel cleanse, participants ingested a total of 28 capsules over two consecutive days. Capsules from individual donors and participant stool samples collected at baseline, 6, 12, and 26 weeks post-treatment were analyzed by shotgun metagenomic sequencing allowing us to track bacterial strain engraftment and its functional implications on recipients' gut microbiomes.<br><br>RESULTS: Multi-donor FMT sustainably altered the structure and the function of the gut microbiome. In what was effectively a microbiome competition experiment, we discovered that two donor microbiomes (one female, one male) dominated strain engraftment and were characterized by high microbial diversity and a high Prevotella to Bacteroides (P/B) ratio. Engrafted strains led to enterotype-level shifts in community composition and provided genes that altered the metabolic potential of the community. Despite our attempts to standardize FMT dose and origin, FMT recipients varied widely in their engraftment of donor strains.<br><br>CONCLUSION: Our study provides evidence for the existence of FMT super-donors whose microbiomes are highly effective at engrafting in the recipient gut. Dominant engrafting male and female donor microbiomes harbored diverse microbial species and genes and were characterized by a high P/B ratio. Yet, the high variability of strain engraftment among FMT recipients suggests the host environment also plays a critical role in mediating FMT receptivity.<br><br>TRIAL REGISTRATION: The Gut Bugs trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615001351505).<br><br>TRIAL PROTOCOL: The trial protocol is available at https://bmjopen.bmj.com/content/9/4/e026174 . Video Abstract.}, }
@article {pmid33985520, year = {2021}, author = {Kuai, XY and Yao, XH and Xu, LJ and Zhou, YQ and Zhang, LP and Liu, Y and Pei, SF and Zhou, CL}, title = {Evaluation of fecal microbiota transplantation in Parkinson's disease patients with constipation.}, journal = {Microbial cell factories}, volume = {20}, number = {1}, pages = {98}, pmid = {33985520}, issn = {1475-2859}, support = {LCZX201814//Suzhou Health and Family Planning Commission/ ; SYSD2020142//Suzhou Municipal Science and Technology Bureau/ ; }, abstract = {Parkinson's disease (PD) is a neurodegenerative disorder and 70-80% of PD patients suffer from gastrointestinal dysfunction such as constipation. We aimed to assess the efficacy and safety of fecal microbiota transplantation (FMT) for treating PD related to gastrointestinal dysfunction. We conducted a prospective, single- study. Eleven patients with PD received FMT. Fecal samples were collected before and after FMT and subjected to 16S ribosomal DNA (rDNA) gene sequencing. Hoehn-Yahr (H-Y) grade, Unified Parkinson's Disease Rating Scale (UPDRS) score, and the Non-Motion Symptom Questionnaire (NMSS) were used to assess improvements in motor and non-motor symptoms. PAC-QOL score and Wexner constipation score were used to assess the patient's constipation symptoms. All patients were tested by the small intestine breath hydrogen test, performed before and after FMT. Community richness (chao) and microbial structure in before-FMT PD patients were significantly different from the after-FMT. We observed an increased abundance of Blautia and Prevotella in PD patients after FMT, while the abundance of Bacteroidetes decreased dramatically. After FMT, the H-Y grade, UPDRS, and NMSS of PD patients decreased significantly. Through the lactulose H2 breath test, the intestinal bacterial overgrowth (SIBO) in PD patients returned to normal. The PAC-QOL score and Wexner constipation score in after-FMT patients decreased significantly. Our study profiles specific characteristics and microbial dysbiosis in the gut of PD patients. FMT might be a therapeutic potential for reconstructing the gut microbiota of PD patients and improving their motor and non-motor symptoms.}, }
@article {pmid33983361, year = {2021}, author = {Lu, C and Chen, J and Yi, C and Han, J and Shi, Q and Li, J and Liu, B and Zhou, J and Su, X}, title = {Gut microbiota mediated the protective effects of tuna oil on collagen-induced arthritis in mice.}, journal = {Food &amp; function}, volume = {12}, number = {12}, pages = {5387-5398}, doi = {10.1039/d1fo00709b}, pmid = {33983361}, issn = {2042-650X}, abstract = {Rheumatoid arthritis is emerging as a chronic autoimmune disease worldwide. In this study, the beneficial effects of tuna oil (TO) on collagen-induced arthritis (CIA) mice were investigated. Dietary administration of TO relieved arthritis severity and joint bone erosion, and ameliorated systemic inflammation. Furthermore, TO treatments regulated the phosphorylation of nuclear factor-kappa B (NF-κB) and Wnt1/β-catenin signaling pathways in the joint, enhanced osteoblastogenesis biomarkers and suppressed osteoclastogenesis biomarkers, and subsequently re-balanced bone remodeling. Moreover, the impaired intestinal epithelial barrier was repaired after TO treatments, along with gut microbiota modulation. By employing fecal microbiota transplantation, we clarified that the beneficial effects of TO in CIA alleviation were mediated by the modulated gut microbiota. These results indicated that gut microbiota mediated the protective effects of tuna oil on collagen-induced arthritis in mice.}, }
@article {pmid33982930, year = {2021}, author = {Gupta, S and Mullish, BH and Allegretti, JR}, title = {Fecal Microbiota Transplantation: The Evolving Risk Landscape.}, journal = {The American journal of gastroenterology}, volume = {116}, number = {4}, pages = {647-656}, doi = {10.14309/ajg.0000000000001075}, pmid = {33982930}, issn = {1572-0241}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Humans ; Recurrence ; }, abstract = {Fecal microbiota transplantation (FMT) has been recommended in clinical guidelines for the treatment of recurrent Clostridioides difficile infection (CDI). However, it is considered investigational by most regulatory agencies. As the adoption of FMT has increased from a small group of CDI experts alone to more widespread use, there has been a corresponding increase in concern regarding potential risk. FMT is largely considered a safe procedure although risks described range from mild gastrointestinal symptoms to serious infection. Currently, there is variability in how "FMT" is characterized specifically regarding testing approach, which, in turn, impacts the risk profile. This has been highlighted by the rare cases of multidrug-resistant organisms, Shiga toxin-producing Escherichia and enteropathogenic E. coli, recently reported, where these organisms were not screened. These cases have prompted additional screening mandates from the US Food and Drug Administration (FDA), which has maintained its policy of enforcement discretion for the use of FMT for CDI not responding to standard therapy. Here, we examine the evolving risk landscape of FMT.}, }
@article {pmid33982127, year = {2021}, author = {Wang, B and Wang, L and Wang, H and Dai, H and Lu, X and Lee, YK and Gu, Z and Zhao, J and Zhang, H and Chen, W and Wang, G}, title = {Targeting the Gut Microbiota for Remediating Obesity and Related Metabolic Disorders.}, journal = {The Journal of nutrition}, volume = {151}, number = {7}, pages = {1703-1716}, doi = {10.1093/jn/nxab103}, pmid = {33982127}, issn = {1541-6100}, support = {31972052//National Natural Science Foundation of China/ ; JUSRP22006//Fundamental Research Funds for the Central Universities/ ; JUFSTR20180102//Priority Academic Program Development of Jiangsu Higher Education Institutions/ ; BK20180613//Natural Science Foundation of Jiangsu Province/ ; F201923//Jiangsu Province/ ; }, abstract = {The rate of obesity is rapidly increasing and has become a health and economic burden worldwide. As recent studies have revealed that the gut microbiota is closely linked to obesity, researchers have used various approaches to modulate the gut microbiota to treat the condition. Dietary composition and energy intake strongly affect the composition and function of the gut microbiota. Intestinal microbial changes alter the composition of bile acids and fatty acids and regulate bacterial lipopolysaccharide production, all of which influence energy metabolism and immunity. Evidence also suggests that remodeling the gut microbiota through intake of probiotics, prebiotics, fermented foods, and dietary plants, as well as by fecal microbiota transplantation, are feasible methods to remediate obesity.}, }
@article {pmid33981340, year = {2021}, author = {Liu, X and Li, Y and Wu, K and Shi, Y and Chen, M}, title = {Fecal Microbiota Transplantation as Therapy for Treatment of Active Ulcerative Colitis: A Systematic Review and Meta-Analysis.}, journal = {Gastroenterology research and practice}, volume = {2021}, number = {}, pages = {6612970}, pmid = {33981340}, issn = {1687-6121}, abstract = {Aim: Increasing evidence supports the role of the gut microbiota in the etiology of ulcerative colitis (UC). Fecal microbiota transplantation (FMT) is a highly effective treatment against recurrent Clostridium difficile infection; however, its efficacy in UC is still controversial. A systematic review and meta-analysis was conducted to evaluate the efficacy and safety of FMT for treatment of active UC.<br><br>Methods: We searched Cochrane, Medline, Web of Science, and Embase from inception to February 2020. Randomized controlled trials (RCTs) recruiting adults with active UC, which compared FMT with controls, were eligible. The primary outcome was combined clinical remission with endoscopic remission/response. Secondary outcomes included clinical remission, endoscopic remission, and serious adverse events. Relative risk (RR) with 95% confidence interval (CI) is reported.<br><br>Results: Five RCTs with 292 participants were eligible for inclusion. When data were pooled for all patients, FMT was associated with a higher combined clinical remission with endoscopic remission/response; the RR of combined outcome not achieving after FMT vs. control was 0.79 (95% CI 0.70-0.88). FMT delivered via lower gastrointestinal route was superior to upper gastrointestinal route with regard to combined clinical remission with endoscopic remission/response (RR = 0.79, 95% CI 0.70-0.89). FMT with pooled donor stool (RR = 0.69, 95% CI 0.56-0.85) and higher frequency of administration (RR = 0.76, 95% CI 0.62-0.93) may be more effective with regard to clinical remission. There was no statistically significant difference in serious adverse events with FMT compared with controls (RR = 0.98, 95% CI 0.93-1.03).<br><br>Conclusion: FMT shows a promising perspective with comparable safety and favorable clinical efficacy for the treatment of active UC in the short term. However, further larger, more rigorously conducted RCTs of FMT in UC are still needed in order to resolve the controversial questions.}, }
@article {pmid33978386, year = {2021}, author = {Yang, X and Huang, Z and He, J and Chen, Y}, title = {The Elevated Risk of Recurrent Clostridioides Difficile Infection in Patients with Inflammatory Bowel Disease: a Systematic Review and Meta-analysis.}, journal = {Clinical laboratory}, volume = {67}, number = {5}, pages = {}, doi = {10.7754/Clin.Lab.2020.200428}, pmid = {33978386}, issn = {1433-6510}, mesh = {Clostridioides ; *Clostridium Infections/diagnosis/epidemiology ; *Colitis, Ulcerative/complications/diagnosis ; Fecal Microbiota Transplantation ; Humans ; *Inflammatory Bowel Diseases/complications/diagnosis ; }, abstract = {BACKGROUND: The association between inflammatory bowel disease (IBD) and the risk of recurrent Clostridioides difficile infection (rCDI) is still controversial. This systematic review and meta-analysis aims to clarify whether the risk of rCDI is associated with IBD based on published data.<br><br>METHODS: A systematic review and meta-analysis was conducted in English and Chinese databases, covering all available publications until date 01/01/2020. The statistical analysis was performed by RevMan 5.3 and odds ratios (ORs) combined with 95% confidence intervals (CI) were calculated to explore the IBD-rCDI association.<br><br>RESULTS: A total of 4,417 IBD cases and 355,769 control cases in 14 independent studies from 2007 to 2019 were included. Compared with non-IBD, IBD was associated with an increased risk of rCDI (OR = 1.63, CI = 1.09 - 2.43, p = 0.02). In addition, the risk of rCDI was particularly and significantly increased in IBD patients at the young age (≤ 50, OR = 1.58, CI = 1.02 - 2.44, p = 0.04), but not in patients at the old age (> 50, OR = 2.08, CI = 0.65 - 6.61, p = 0.21). Compared with Crohn's disease (CD), no significant differences existed in the risk of rCDI in ulcerative colitis (UC) (OR = 1.22, CI = 0.81 - 1.85, p = 0.34). Additionally, the risk of rCDI was not significantly different between UC and CD, in patients receiving FMT (OR = 1.41, CI = 0.65 - 3.06, p = 0.38) or no FMT treatment (OR = 1.16, CI = 0.71 - 1.88, p = 0.56).<br><br>CONCLUSIONS: The risk of rCDI was significantly increased in IBD patients, in particular in those age below 50. Compared with CD, no significant differences of the risk of rCDI was observed in UC.}, }
@article {pmid33966043, year = {2021}, author = {Derosa, L and Zitvogel, L}, title = {Fecal microbiota transplantation: can it circumvent resistance to PD-1 blockade in melanoma?.}, journal = {Signal transduction and targeted therapy}, volume = {6}, number = {1}, pages = {178}, pmid = {33966043}, issn = {2059-3635}, }
@article {pmid33961887, year = {2021}, author = {Pai, N and Popov, J and Hill, L and Hartung, E and Grzywacz, K and Moayyedi, P and , }, title = {Results of the First Pilot Randomized Controlled Trial of Fecal Microbiota Transplant In Pediatric Ulcerative Colitis: Lessons, Limitations, and Future Prospects.}, journal = {Gastroenterology}, volume = {161}, number = {2}, pages = {388-393.e3}, doi = {10.1053/j.gastro.2021.04.067}, pmid = {33961887}, issn = {1528-0012}, }
@article {pmid33961710, year = {2021}, author = {Singh, AR and Sachan, A and Shankar, S}, title = {Letter: faecal microbiota transplant in Clostridioides difficile infection: learning from the common water hyacinth.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {53}, number = {11}, pages = {1244-1245}, doi = {10.1111/apt.16370}, pmid = {33961710}, issn = {1365-2036}, mesh = {Clostridioides ; *Clostridium Infections/therapy ; *Eichhornia ; Fecal Microbiota Transplantation ; Humans ; Vancomycin ; Water ; }, }
@article {pmid33959193, year = {2021}, author = {Yadav, D and Khanna, S}, title = {Safety of fecal microbiota transplantation for Clostridioides difficile infection focusing on pathobionts and SARS-CoV-2.}, journal = {Therapeutic advances in gastroenterology}, volume = {14}, number = {}, pages = {17562848211009694}, pmid = {33959193}, issn = {1756-283X}, abstract = {Clostridioides difficile infection (CDI) is a consequence of flagrant use of antibiotics, an aging population with increasing comorbidities, and increased hospitalizations. The treatment of choice for CDI is antibiotics (vancomycin or fidaxomicin), with a possibility of recurrent CDI despite lack of additional risk factors for CDI. For the last 10 years, fecal microbiota transplantation (FMT) has emerged as a promising therapy for recurrent CDI, with success rates of over 85% compared with less than 50% with antibiotics for multiple recurrent CDI. Along with the success of FMT, several adverse and serious adverse events with FMT have been reported. These range from self-limiting abdominal pain to death due to severe sepsis. This review focuses on the safety of FMT, emphasizing the reports of transmission of pathobionts like extended-spectrum beta lactamase Escherichia coli and Shiga toxin-producing E. coli. The severe acute respiratory syndrome coronavirus-2 is a potential pathogen that could be transmitted via FMT during the COVID-19 pandemic. The challenges faced by clinicians for donor screening, clinical trials, and other aspects of FMT during the pandemic are discussed.}, }
@article {pmid33958592, year = {2021}, author = {Chen, PJ and Nakano, T and Lai, CY and Chang, KC and Chen, CL and Goto, S}, title = {Daily full spectrum light exposure prevents food allergy-like allergic diarrhea by modulating vitamin D3 and microbiota composition.}, journal = {NPJ biofilms and microbiomes}, volume = {7}, number = {1}, pages = {41}, pmid = {33958592}, issn = {2055-5008}, mesh = {Activities of Daily Living ; Animals ; Antibody Formation/immunology ; Biomarkers ; Cholecalciferol/*metabolism ; Cytokines/metabolism ; Diarrhea/*etiology/*prevention &amp; control ; Disease Management ; Disease Models, Animal ; Disease Susceptibility ; Dysbiosis ; Environmental Exposure ; Fecal Microbiota Transplantation/methods ; Female ; Food Hypersensitivity/*etiology/*prevention &amp; control ; *Gastrointestinal Microbiome ; Humans ; Intestinal Mucosa/immunology/metabolism/pathology ; Mice ; Oxidative Stress ; Phototherapy ; *Sunlight ; T-Lymphocytes/immunology/metabolism ; }, abstract = {The importance of sun exposure on human health is well recognized, and a recent trend in the avoidance of sun exposure has led to the risk of missing the beneficial effects such as vitamin D3 biogenesis. Vitamin D3 insufficiency is one of the risk factors for the development of food allergies (FAs), and vitamin D3 status controls gut homeostasis by modulating the microbiota. This study aimed to explore the impact of daily full spectrum light exposure (phototherapy) on the pathogenesis of FAs. Phototherapy ameliorated allergic diarrhea and improved FA-associated vitamin D3 insufficiency and dysbiosis. Fecal microbiota transplantation (FMT) of FA donor feces induced allergic diarrhea with OVA-specific IgE elevation in naïve mice. In contrast, FMT of naïve donor feces ameliorated allergic diarrhea in established FA mice, suggesting the involvement of the microbiota composition in FA. Phototherapy is an alternative approach for the prevention of FA-like allergic diarrhea through the modulation of vitamin D3 status and microbiota composition.}, }
@article {pmid33957682, year = {2021}, author = {Hartmann, P and Schnabl, B}, title = {New Developments in Microbiome in Alcohol-Associated and Nonalcoholic Fatty Liver Disease.}, journal = {Seminars in liver disease}, volume = {41}, number = {1}, pages = {87-102}, pmid = {33957682}, issn = {1098-8971}, support = {R01 AA020703/AA/NIAAA NIH HHS/United States ; National Institutes of Health//R01 AA020703/ ; Biomedical Laboratory Research &amp; Development Service of the VA Office of Research and Development//P30 DK120515/ ; National Institutes of Health//K12 HD85036/ ; I01 BX004594/BX/BLRD VA/United States ; P30 DK120515/DK/NIDDK NIH HHS/United States ; R01 AA024726/AA/NIAAA NIH HHS/United States ; National Institutes of Health//R01 AA24726/ ; National Institutes of Health//BX004594/ ; P50 AA011999/AA/NIAAA NIH HHS/United States ; Biomedical Laboratory Research &amp; Development Service of the VA Office of Research and Development//P50 AA011999/ ; U01 AA026939/AA/NIAAA NIH HHS/United States ; National Institutes of Health//U01 AA026939/ ; }, abstract = {Alcohol-associated liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are important causes of morbidity and mortality worldwide. The intestinal microbiota is involved in the development and progression of both ALD and NAFLD. Here we describe associated changes in the intestinal microbiota, and we detail randomized clinical trials in ALD and NAFLD which evaluate treatments modulating the intestinal microbiome including fecal microbiota transplantation, probiotics, prebiotics, synbiotics, and antibiotics. Finally, we discuss precision medicine approaches targeting the intestinal microbiome to ameliorate ALD and NAFLD.}, }
@article {pmid33953692, year = {2021}, author = {Smitka, K and Prochazkova, P and Roubalova, R and Dvorak, J and Papezova, H and Hill, M and Pokorny, J and Kittnar, O and Bilej, M and Tlaskalova-Hogenova, H}, title = {Current Aspects of the Role of Autoantibodies Directed Against Appetite-Regulating Hormones and the Gut Microbiome in Eating Disorders.}, journal = {Frontiers in endocrinology}, volume = {12}, number = {}, pages = {613983}, pmid = {33953692}, issn = {1664-2392}, abstract = {The equilibrium and reciprocal actions among appetite-stimulating (orexigenic) and appetite-suppressing (anorexigenic) signals synthesized in the gut, brain, microbiome and adipose tissue (AT), seems to play a pivotal role in the regulation of food intake and feeding behavior, anxiety, and depression. A dysregulation of mechanisms controlling the energy balance may result in eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). AN is a psychiatric disease defined by chronic self-induced extreme dietary restriction leading to an extremely low body weight and adiposity. BN is defined as out-of-control binge eating, which is compensated by self-induced vomiting, fasting, or excessive exercise. Certain gut microbiota-related compounds, like bacterial chaperone protein Escherichia coli caseinolytic protease B (ClpB) and food-derived antigens were recently described to trigger the production of autoantibodies cross-reacting with appetite-regulating hormones and neurotransmitters. Gut microbiome may be a potential manipulator for AT and energy homeostasis. Thus, the regulation of appetite, emotion, mood, and nutritional status is also under the control of neuroimmunoendocrine mechanisms by secretion of autoantibodies directed against neuropeptides, neuroactive metabolites, and peptides. In AN and BN, altered cholinergic, dopaminergic, adrenergic, and serotonergic relays may lead to abnormal AT, gut, and brain hormone secretion. The present review summarizes updated knowledge regarding the gut dysbiosis, gut-barrier permeability, short-chain fatty acids (SCFA), fecal microbial transplantation (FMT), blood-brain barrier permeability, and autoantibodies within the ghrelin and melanocortin systems in eating disorders. We expect that the new knowledge may be used for the development of a novel preventive and therapeutic approach for treatment of AN and BN.}, }
@article {pmid33947987, year = {2021}, author = {Panwar, RB and Sequeira, RP and Clarke, TB}, title = {Microbiota-mediated protection against antibiotic-resistant pathogens.}, journal = {Genes and immunity}, volume = {}, number = {}, pages = {}, pmid = {33947987}, issn = {1476-5470}, support = {107660/Z/15Z//Wellcome Trust (Wellcome)/ ; }, abstract = {Colonization by the microbiota provides one of our most effective barriers against infection by pathogenic microbes. The microbiota protects against infection by priming immune defenses, by metabolic exclusion of pathogens from their preferred niches, and through direct antimicrobial antagonism. Disruption of the microbiota, especially by antibiotics, is a major risk factor for bacterial pathogen colonization. Restoration of the microbiota through microbiota transplantation has been shown to be an effective way to reduce pathogen burden in the intestine but comes with a number of drawbacks, including the possibility of transferring other pathogens into the host, lack of standardization, and potential disruption to host metabolism. More refined methods to exploit the power of the microbiota would allow us to utilize its protective power without the drawbacks of fecal microbiota transplantation. To achieve this requires detailed understanding of which members of the microbiota protect against specific pathogens and the mechanistic basis for their effects. In this review, we will discuss the clinical and experimental evidence that has begun to reveal which members of the microbiota protect against some of the most troublesome antibiotic-resistant pathogens: Klebsiella pneumoniae, vancomycin-resistant enterococci, and Clostridioides difficile.}, }
@article {pmid33947457, year = {2021}, author = {Xu, B and Qin, W and Yan, Y and Tang, Y and Zhou, S and Huang, J and Xie, C and Ma, L and Yan, X}, title = {Gut microbiota contributes to the development of endometrial glands in gilts during the ovary-dependent period.}, journal = {Journal of animal science and biotechnology}, volume = {12}, number = {1}, pages = {57}, pmid = {33947457}, issn = {1674-9782}, support = {2018CFA020//Natural Science Foundation of Hubei Province/ ; }, abstract = {BACKGROUND: The hyper-prolificacy Meishan gilts achieved a superior endometrial gland development (EGD) than white crossbred gilts during the ovary-independent period (before 60 d of age). Then, the EGD continues under the management of ovary-derived steroid hormones that regulated by gut microbiota (after 60 d of age). However, whether Meishan gilts' superiority in EGD lasting to the ovary-dependent period (after 60 d of age) and the role of gut microbiota in this period both remain unclear.<br><br>METHODS: Meishan gilts and Landrace x Yorkshire (LxY) gilts were raised under the same housing and feeding conditions until sexual maturity and then we compared their EGD and gut microbiota. Meanwhile, we transplanted fecal microbiota from Meishan gilts to L×Y gilts to explore the role of gut microbiota in EGD. We sampled plasma every 3 weeks and collected the uterus, ovary, liver, and rectal feces after the sacrifice. We then determined the hormone concentrations and expressions of the EGD-related genes. We also profiled the gut microbiota using 16S rDNA sequencing and metabolites of plasma and liver tissue using untargeted metabolomics. Finally, the correlation analysis and significant test was conducted between FMT-shifted gut microbes and EGD-related indices.<br><br>RESULTS: Meishan gilts have larger endometrial gland area (P < 0.001), longer uterine horn length (P < 0.01) but lighter uterine horn weight (P < 0.05), a distinctive gut microbiota compared with L×Y gilts. Fecal microbiota transplantation (FMT) increased endometrial gland area (P < 0.01). FMT markedly shifted the metabolite profiles of both liver and plasma, and these differential metabolites enriched in steroid hormone biosynthesis pathway. FMT increased estradiol and insulin-like growth factor 1 but decreased progesterone dynamically. FMT also increased the expression of the EGD-related genes estrogen receptor 1 gene, epithelial cadherin, and forkhead box protein A2. There is a significant correlation between FMT-shifted gut microbes and EGD-related indices.<br><br>CONCLUSION: Sexually matured Meishan gilts achieved a superior EGD than LxY gilts. Meanwhile, gut microbiota contribute to the EGD potentially via regulating of steroid hormones during the ovary-dependent period.}, }
@article {pmid33947304, year = {2021}, author = {Han, JX and Tao, ZH and Qian, Y and Yu, CY and Li, J and Kang, ZR and Lu, S and Xie, Y and Hong, J and Chen, H and Chen, YX and Fang, JY}, title = {ZFP90 drives the initiation of colitis-associated colorectal cancer via a microbiota-dependent strategy.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1-20}, pmid = {33947304}, issn = {1949-0984}, abstract = {Chronic inflammation and gut microbiota dysbiosis are risk factors for colorectal cancer. In clinical practice, patients with inflammatory bowel disease (IBD) have a greatly increased risk of developing colitis-associated colorectal cancer (CAC). However, the underlying mechanism of the initiation of CAC remains unknown. Systematic analyses using an existing genome-wide association study (GWAS) and conditional deletion of Zfp90 (encoding zinc finger protein 90 homolog) in a CAC mouse model indicated that Zfp90 is a putative oncogene in CAC development.Strikingly, depletion of the gut microbiota eliminated the tumorigenic effect of Zfp90 in the CAC mouse model. Moreover, fecal microbiota transplantation demonstrated that Zfp90 promoted CAC dependent on the gut microbiota. Analysis of 16s rDNA sequences in fecal specimens from the CAC mouse model allowed us to speculate that a Prevotella copri-defined microbiota might mediate the oncogenic role of Zfp90 in the development of CAC. Mechanistic studies revealed Zfp90 accelerated CAC development through the TLR4-PI3K-AKT-NF-κB pathway. Our findings revealed the crucial role of the Zfp90-microbiota-NF-κB axis in creating a tumor-promoting environment and suggested therapeutic targets for CAC prevention and treatment.}, }
@article {pmid33946812, year = {2021}, author = {Kouidhi, S and Zidi, O and Alhujaily, M and Souai, N and Mosbah, A and Belali, TM and Ghedira, K and El Kossai, I and El Manaa, J and Mnif, W and Cherif, A}, title = {Fecal Metabolomics Reveals Distinct Profiles of Kidney Transplant Recipients and Healthy Controls.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {11}, number = {5}, pages = {}, pmid = {33946812}, issn = {2075-4418}, abstract = {Monitoring graft recipients remains dependent on traditional biomarkers and old technologies lacking specificity, sensitivity, or accuracy. Recently, metabolomics is becoming a promising approach that may offer to kidney transplants a more effective and specific monitoring. Furthermore, emerging evidence suggested a fundamental role of gut microbiota as an important determinant of patients' metabolomes. In the current study, we enrolled forty stable renal allografts recipients compared to twenty healthy individuals. Samples were taken at different time points from patient to patient following transplantation surgery, which varied from 3 months to 22 years post-graft. All patients started the immunosuppression therapy immediately following kidney graft (Day 0). Gas chromatography-mass spectrometry (GC-MS) was employed to perform untargeted analysis of fecal metabolites. Globally, the fecal metabolic signature was significantly different between kidney transplants and the control group. Fecal metabolome was dominated by lipids (sterols and fatty acids) in the stable transplant group compared to the controls (p < 0.05). Overall, 18 metabolites were significantly altered within kidney transplant recipients. Furthermore, the most notable altered metabolic pathways in kidney transplants include ubiquinone and other terpenoid-quinone biosynthesis, tyrosine metabolism, tryptophan biosynthesis, and primary bile acid biosynthesis. Fecal metabolites could effectively distinguish stable transplant recipients from controls, supporting the potential utility of metabolomics in rapid and non-invasive diagnosis to produce relevant biomarkers and to help clinicians in monitoring kidney transplants. Further investigations are needed to clarify the physiological relevance of fecal metabolome and to assess the impact of microbiota modulation.}, }
@article {pmid33946610, year = {2021}, author = {Karaduta, O and Dvanajscak, Z and Zybailov, B}, title = {Metaproteomics-An Advantageous Option in Studies of Host-Microbiota Interaction.}, journal = {Microorganisms}, volume = {9}, number = {5}, pages = {}, pmid = {33946610}, issn = {2076-2607}, support = {P20GM121293//NIH Center of Biomedical Research Excellence/ ; }, abstract = {Gut microbiome contributes to host health by maintaining homeostasis, increasing digestive efficiency, and facilitating the development of the immune system. Manipulating gut microbiota is being recognized as a therapeutic target to manage various chronic diseases. The therapeutic manipulation of the intestinal microbiome is achieved through diet modification, the administration of prebiotics, probiotics, or antibiotics, and more recently, fecal microbiome transplantation (FMT). In this opinion paper, we give a perspective on the current status of application of multi-omics technologies in the analysis of host-microbiota interactions. The aim of this paper was to highlight the strengths of metaproteomics, which integrates with and often relies on other approaches.}, }
@article {pmid33938391, year = {2021}, author = {Rubio-Del-Campo, A and Gozalbo-Rovira, R and Moya-Gonzálvez, EM and Alberola, J and Rodríguez-Díaz, J and Yebra, MJ}, title = {Infant gut microbiota modulation by human milk disaccharides in humanized microbiome mice.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1-20}, pmid = {33938391}, issn = {1949-0984}, abstract = {Human milk glycans present a unique diversity of structures that suggest different mechanisms by which they may affect the infant microbiome development. A humanized mouse model generated by infant fecal transplantation was utilized here to evaluate the impact of fucosyl-α1,3-GlcNAc (3FN), fucosyl-α1,6-GlcNAc, lacto-N-biose (LNB) and galacto-N-biose on the fecal microbiota and host-microbiota interactions. 16S rRNA amplicon sequencing showed that certain bacterial genera significantly increased (Ruminococcus and Oscillospira) or decreased (Eubacterium and Clostridium) in all disaccharide-supplemented groups. Interestingly, cluster analysis differentiates the consumption of fucosyl-oligosaccharides from galactosyl-oligosaccharides, highlighting the disappearance of Akkermansia genus in both fucosyl-oligosaccharides. An increment of the relative abundance of Coprococcus genus was only observed with 3FN. As well, LNB significantly increased the relative abundance of Bifidobacterium, whereas the absolute levels of this genus, as measured by quantitative real-time PCR, did not significantly increase. OTUs corresponding to the species Bifidobacterium longum, Bifidobacterium adolescentis and Ruminococcus gnavus were not present in the control after the 3-week intervention, but were shared among the donor and specific disaccharide groups, indicating that their survival is dependent on disaccharide supplementation. The 3FN-feeding group showed increased levels of butyrate and acetate in the colon, and decreased levels of serum HDL-cholesterol. 3FN also down-regulated the pro-inflammatory cytokine TNF-α and up-regulated the anti-inflammatory cytokines IL-10 and IL-13, and the Toll-like receptor 2 in the large intestine tissue. The present study revealed that the four disaccharides show efficacy in producing beneficial compositional shifts of the gut microbiota and in addition, the 3FN demonstrated physiological and immunomodulatory roles.}, }
@article {pmid33937093, year = {2021}, author = {Li, Y and Xia, S and Jiang, X and Feng, C and Gong, S and Ma, J and Fang, Z and Yin, J and Yin, Y}, title = {Gut Microbiota and Diarrhea: An Updated Review.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {625210}, pmid = {33937093}, issn = {2235-2988}, mesh = {Animals ; Diarrhea ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Probiotics ; }, abstract = {Diarrhea is a common problem to the whole world and the occurrence of diarrhea is highly associated with gut microbiota, such as bacteria, fungi, and viruses. Generally, diarrheal patients or animals are characterized by gut microbiota dysbiosis and pathogen infections may lead to diarrheal phenotypes. Of relevance, reprograming gut microbiota communities by dietary probiotics or fecal bacteria transplantation are widely introduced to treat or prevent diarrhea. In this review, we discussed the influence of the gut microbiota in the infection of diarrhea pathogens, and updated the research of reshaping the gut microbiota to prevent or treat diarrhea for the past few years. Together, gut microbiota manipulation is of great significance to the prevention and treatment of diarrhea, and further insight into the function of the gut microbiota will help to discover more anti-diarrhea probiotics.}, }
@article {pmid33937092, year = {2021}, author = {Chen, J and Zaman, A and Ramakrishna, B and Olesen, SW}, title = {Stool Banking for Fecal Microbiota Transplantation: Methods and Operations at a Large Stool Bank.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {622949}, pmid = {33937092}, issn = {2235-2988}, mesh = {*Clostridium Infections/therapy ; Donor Selection ; *Fecal Microbiota Transplantation ; Feces ; Humans ; Tissue Donors ; }, abstract = {Objectives: Fecal microbiota transplantation (FMT) is a recommended therapy for recurrent Clostridioides difficile infection and is being investigated as a potential therapy for dozens of microbiota-mediated indications. Stool banks centralize FMT donor screening and FMT material preparation with the goal of expanding access to FMT material while simultaneously improving its safety, quality, and convenience. Although there are published consensuses on donor screening guidelines, there are few reports about the implementation of those guidelines in functioning stool banks.<br><br>Methods: To help inform consensus standards with data gathered from real-world settings and, in turn, to improve patient care, here we describe the general methodology used in 2018 by OpenBiome, a large stool bank, and its outputs in that year.<br><br>Results: In 2018, the stool bank received 7,536 stool donations from 210 donors, a daily average of 20.6 donations, and processed 4,271 of those donations into FMT preparations. The median time a screened and enrolled stool donor actively donated stool was 5.8 months. The median time between the manufacture of an FMT preparation and its shipment to a hospital or physician was 8.9 months. Half of the stool bank's partner hospitals and physicians ordered an average of 0.75 or fewer FMT preparations per month.<br><br>Conclusions: Further knowledge sharing should help inform refinements of stool banking guidelines and best practices.}, }
@article {pmid33934412, year = {2021}, author = {Goeser, F and Sifft, B and Stein-Thoeringer, C and Farowski, F and Strassburg, CP and Brossart, P and Higgins, PG and Scheid, C and Wolf, D and Holderried, TAW and Vehreschild, MJGT and Cruz Aguilar, MR}, title = {Fecal microbiota transfer for refractory intestinal graft-versus-host disease - Experience from two German tertiary centers.}, journal = {European journal of haematology}, volume = {107}, number = {2}, pages = {229-245}, doi = {10.1111/ejh.13642}, pmid = {33934412}, issn = {1600-0609}, abstract = {RATIONALE: Steroid refractory graft-vs-host disease (sr-GvHD) represents a challenging complication after allogeneic hematopoietic cell transplantation (allo-HCT). Intestinal microbiota (IM) diversity and dysbiosis were identified as influencing factors for the development of acute GvHD. Fecal microbiota transfer (FMT) is hypothesized to restore IM dysbiosis, but there is limited knowledge about the significance of FMT in the treatment of sr-GvHD.<br><br>OBJECTIVES: We studied the effects of FMT on sr-GvHD in allo-HCT patients from two German tertiary clinical centers (n = 11 patients; period: March 2017 until July 2019). To assess safety and clinical efficacy, we analyzed clinical data pre- and post-FMT (day -14 to +30 relative to FMT). Moreover, IM were analyzed in donor samples and in a subset of patients pre- and post-FMT by 16S rRNA sequencing.<br><br>RESULTS: Post-FMT, we observed no intervention-associated, systemic inflammatory responses and only minor side effects (5/11 patients: abdominal pain and transformation of peristalsis-each 3/11 and vomiting-1/11). Stool frequencies and volumes were significantly reduced [pre- vs post-FMT (d14): P < .05, respectively] as well as clear attenuation regarding both grading and staging of sr-GvHD was present upon FMT. Moreover, IM analyses revealed an increase of alpha diversity as well as a compositional shifts toward the donor post-FMT.<br><br>CONCLUSIONS: In our study, we observed positive effects on sr-GVHD after FMT without the occurrence of major adverse events. Although these findings are in line with published data on beneficial effects of FMT in sr-GvHD, further randomized clinical studies are urgently needed to better define the clinical validity including mode of action.}, }
@article {pmid33928112, year = {2021}, author = {Wu, C and Lyu, W and Hong, Q and Zhang, X and Yang, H and Xiao, Y}, title = {Gut Microbiota Influence Lipid Metabolism of Skeletal Muscle in Pigs.}, journal = {Frontiers in nutrition}, volume = {8}, number = {}, pages = {675445}, pmid = {33928112}, issn = {2296-861X}, abstract = {Gut microbiota is recognized as a strong determinant of host physiology including fat metabolism and can transfer obesity-associated phenotypes from donors to recipients. However, the relationship between gut microbiota and intramuscular fat (IMF) is still largely unknown. Obese Jinhua pigs (JP) have better meat quality that is associated with higher IMF content than lean Landrace pigs (LP). The present study was conducted to test the contribution of gut microbiota to IMF properties by transplanting fecal microbiota of adult JP and LP to antibiotics-treated mice. Similar to JP donors, the mice receiving JP's microbiota (JM) had elevated lipid and triglyceride levels and the lipoprotein lipase activity, as well as reduced mRNA level of angiopoietin-like 4 (ANGPTL4) in the gastrocnemius muscles, compared to those in mice receiving LP's microbiota (LM). High-throughput 16S rRNA sequencing confirmed that transplantation of JP and LP feces differently reconstructed the gut microbiota in both jejunum and colon of mouse recipients. In colonic samples, we observed an elevated ratio of Firmicutes to Bacteroidetes and increased abundance of genus Romboutsia in JM, which were positively correlated with obesity. Furthermore, the abundance of Akkermansia decreased in JM, which is positively correlated with lean. Colonic concentrations of acetate (P = 0.047) and butyrate (P = 0.014) were significantly lower in JM than in LM, and consistently, the terminal genes for butyrate synthesis, butyryl CoA: acetate CoA transferase were less abundant in colonic microbiota of JM. Taken together, these gut microbiota of obese JP intrinsically promotes IMF accumulation and can transfer the properties to mouse recipients. Manipulation of intestinal microbiota will, therefore, have the potential to improve the meat quality and flavor of pigs and even to ameliorate the metabolic syndrome in human.}, }
@article {pmid33928033, year = {2021}, author = {Li, W and Deng, X and Chen, T}, title = {Exploring the Modulatory Effects of Gut Microbiota in Anti-Cancer Therapy.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {644454}, pmid = {33928033}, issn = {2234-943X}, abstract = {In the recent decade, gut microbiota has received growing interest due to its role in human health and disease. On the one hand, by utilizing the signaling pathways of the host and interacting with the immune system, the gut microbiota is able to maintain the homeostasis in human body. This important role is mainly modulated by the composition of microbiota, as a normal microbiota composition is responsible for maintaining the homeostasis of human body, while an altered microbiota profile could contribute to several pathogenic conditions and may further lead to oncogenesis and tumor progression. Moreover, recent insights have especially focused on the important role of gut microbiota in current anticancer therapies, including chemotherapy, radiotherapy, immunotherapy and surgery. Research findings have indicated a bidirectional interplay between gut microbiota and these therapeutic methods, in which the implementation of different therapeutic methods could lead to different alterations in gut microbiota, and the presence of gut microbiota could in turn contribute to different therapeutic responses. As a result, manipulating the gut microbiota to reduce the therapy-induced toxicity may provide an adjuvant therapy to achieve a better therapeutic outcome. Given the complex role of gut microbiota in cancer treatment, this review summarizes the interactions between gut microbiota and anticancer therapies, and demonstrates the current strategies for reshaping gut microbiota community, aiming to provide possibilities for finding an alternative approach to lower the damage and improve the efficacy of cancer therapy.}, }
@article {pmid33927926, year = {2021}, author = {Scibelli, N and Singh, P and Raynor, K}, title = {Intestinal Dysbiosis Disguised as a Rectal Fistula Treated With Autologous Fecal Microbiota Transplantation.}, journal = {Cureus}, volume = {13}, number = {3}, pages = {e14115}, pmid = {33927926}, issn = {2168-8184}, abstract = {Fecal microbiota transplantation (FMT) has been efficacious in the treatment of intestinal dysbiosis, derangement of the native intestinal microflora, and the indications for autologous FMT are growing. A 69-year-old Caucasian man with a past medical history of paraplegia secondary to motor vehicle accident and sigmoid-end colostomy presented to his gastroenterologist with the complaint of rectal discharge. A complicated medical course pre-dated his presentation and included multiple decubitus ulcers requiring debridement and several courses of broad-spectrum antibiotics. The rectal discharge was initially presumed to be from a fistula leading to one of his ulcers; however, workup with anoscopy, flexible sigmoidoscopy, and magnetic resonance imaging of the pelvis showed no visible perirectal abscess or connection to the sigmoid colon through a fistula. Intestinal dysbiosis was an alternative theory considered to be the cause of his copious rectal discharge due to his several courses of broad-spectrum antibiotics and prolonged inactivity of his gut. This prompted a trial treatment plan utilizing autologous FMT, with the patient administering enemas containing his own stool to the distal limb of his bowel. As a result of this treatment, the patient's chief complaint completely resolved within days of initiating treatment, although symptoms did eventually return. We would like to propose that further randomized studies should be done to investigate autologous FMT as a treatment for patients suffering from intestinal dysbiosis following sigmoid-end colostomy.}, }
@article {pmid33926254, year = {2021}, author = {Zhang, L and Ma, X and Liu, P and Ge, W and Hu, L and Zuo, Z and Xiao, H and Liao, W}, title = {Treatment and mechanism of fecal microbiota transplantation in mice with experimentally induced ulcerative colitis.}, journal = {Experimental biology and medicine (Maywood, N.J.)}, volume = {246}, number = {13}, pages = {1563-1575}, pmid = {33926254}, issn = {1535-3699}, abstract = {Restoring intestinal microbiota dysbiosis with fecal microbiota transplantation is considered as a promising treatment for ulcerative colitis. However, the mechanisms underlying its relieving effects remain unclear. Ulcerative colitis pathogenesis is associated with the involvement of immune cells and inflammatory cytokines. Here, we aimed to investigate the effect of fecal microbiota transplantation on T cell cytokines in a dextran sulfate sodium-induced ulcerative colitis mouse model. Five-aminosalicylic acid (5-ASA) was used as the positive control. Male C57BL/6 mice were randomly assigned to control, model (UC), UC + FMT, and UC + 5-ASA groups. Each group consisted of five mice. The establishment of the mouse model was verified by fecal occult-blood screening and hematoxylin-eosin staining. Results showed that fecal microbiota transplantation reduced colonic inflammation, significantly decreased T helper (Th)1 and Th17 cells, interferon-gamma, interleukin-2 and interleukin-17, as well as significantly increased Th2 and regulatory T (Treg) cells, interleukin-4, interleukin-10, and transforming growth factor-beta, and improved routine blood count. Furthermore, 16S rRNA gene-sequencing analysis showed a significant increase in the relative abundance of genus Akkermansia and a significant decrease in the relative abundance of genus Helicobacter in the ulcerative colitis group. Fecal microbiota transplantation restored the profile of the intestinal microbiota to that of the control group. These findings demonstrated the capability of fecal microbiota transplantation in controlling experimentally induced ulcerative colitis by improving Th1/Th2 and Th17/Treg imbalance through the regulation of intestinal microbiota.}, }
@article {pmid33926088, year = {2021}, author = {Polak, K and Bergler-Czop, B and Szczepanek, M and Wojciechowska, K and Frątczak, A and Kiss, N}, title = {Psoriasis and Gut Microbiome-Current State of Art.}, journal = {International journal of molecular sciences}, volume = {22}, number = {9}, pages = {}, pmid = {33926088}, issn = {1422-0067}, mesh = {Bacterial Translocation ; Bacteroidetes ; Cardiovascular Diseases/microbiology ; Dysbiosis/physiopathology ; Firmicutes ; Gastrointestinal Microbiome/genetics/*physiology ; Humans ; Inflammatory Bowel Diseases/microbiology ; Microbiota ; Probiotics/therapeutic use ; Psoriasis/*metabolism/*microbiology ; }, abstract = {Psoriasis is a chronic, immune-mediated inflammatory disease that affects around 125 million people worldwide. Several studies concerning the gut microbiota composition and its role in disease pathogenesis recently demonstrated significant alterations among psoriatic patients. Certain parameters such as Firmicutes/Bacteroidetes ratio or Psoriasis Microbiome Index were developed in order to distinguish between psoriatic and healthy individuals. The "leaky gut syndrome" and bacterial translocation is considered by some authors as a triggering factor for the onset of the disease, as it promotes chronic systemic inflammation. The alterations were also found to resemble those in inflammatory bowel diseases, obesity and certain cardiovascular diseases. Microbiota dysbiosis, depletion in SCFAs production, increased amount of produced TMAO, dysregulation of the pathways affecting the balance between lymphocytes populations seem to be the most significant findings concerning gut physiology in psoriatic patients. The gut microbiota may serve as a potential response-to-treatment biomarker in certain cases of biological treatment. Oral probiotics administration as well as fecal microbial transplantation were most reported in bringing health benefits to psoriatic patients. However, the issue of psoriatic bacterial gut composition, its role and healing potential needs further investigation. Here we reviewed the literature on the current state of the relationship between psoriasis and gut microbiome.}, }
@article {pmid33924834, year = {2021}, author = {Clancy, AK and Lee, C and Hamblin, H and Gunaratne, AW and LeBusque, A and Beck, EJ and Dawson, MV and Borody, TJ}, title = {Dietary Intakes of Recipients of Faecal Microbiota Transplantation: An Observational Pilot Study.}, journal = {Nutrients}, volume = {13}, number = {5}, pages = {}, pmid = {33924834}, issn = {2072-6643}, mesh = {Adolescent ; Adult ; Diet/*methods ; *Diet Records ; *Fecal Microbiota Transplantation ; Female ; Humans ; Irritable Bowel Syndrome/*therapy ; Male ; Middle Aged ; Nutrients/*administration &amp; dosage ; Pilot Projects ; Prospective Studies ; Recommended Dietary Allowances ; Surveys and Questionnaires ; Young Adult ; }, abstract = {This study reports on the dietary intake of recipients of faecal microbiota transplantation (FMT), comparing this with dietary guidelines, and investigates the relationship between dietary intake and clinical outcomes. Males and females aged ≥ 16 years with irritable bowel syndrome or inflammatory bowel disease undergoing FMT were invited to complete validated symptom and quality of life (QOL) questionnaires and three-day weighed food diaries. Descriptive statistics were calculated for symptom scores, QOL scores, nutrients, and food group servings, and compared to Australian population norms, nutrient reference values, and dietary guidelines. The relationship between dietary intake, symptoms, and QOL was assessed. Participants (n = 18) reported baseline symptoms of urgency, abdominal pain, nausea, and bloating and reduced QOL. Of the participants who completed food diaries, 8/14 met the recommended 30 g of fibre when including supplements. Participants met the recommendations for micronutrients and food groups except calcium, fruit, and dairy/dairy alternatives. There was a non-significant trend towards lower symptom severity scores in participants who met the fibre target. The high degree of variability in participant fibre intakes highlights diet as a key variable that has not been previously controlled for in FMT intervention studies. Future studies examining FMT should include dietary analysis of habitual intake of the recipients and donors.}, }
@article {pmid33920646, year = {2021}, author = {Nomura, K and Ishikawa, D and Okahara, K and Ito, S and Haga, K and Takahashi, M and Arakawa, A and Shibuya, T and Osada, T and Kuwahara-Arai, K and Kirikae, T and Nagahara, A}, title = {Bacteroidetes Species Are Correlated with Disease Activity in Ulcerative Colitis.}, journal = {Journal of clinical medicine}, volume = {10}, number = {8}, pages = {}, pmid = {33920646}, issn = {2077-0383}, support = {JP16K09328//Japan Society for the Promotion of Science/ ; }, abstract = {Fecal microbiota transplantation following triple-antibiotic therapy (amoxicillin/fosfomycin/metronidazole) improves dysbiosis caused by reduced Bacteroidetes diversity in patients with ulcerative colitis (UC). We investigated the correlation between Bacteroidetes species abundance and UC activity. Fecal samples from 34 healthy controls and 52 patients with active UC (Lichtiger's clinical activity index ≥5 or Mayo endoscopic subscore ≥1) were subjected to next-generation sequencing with HSP60 as a target in bacterial metagenome analysis. A multiplex gene expression assay using colonoscopy-harvested mucosal tissues determined the involvement of Bacteroidetes species in the mucosal immune response. In patients with UC, six Bacteroides species exhibited significantly lower relative abundance, and twelve Bacteroidetes species were found significantly correlated with at least one metric of disease activity. The abundance of five Bacteroidetes species (Alistipes putredinis, Bacteroides stercoris, Bacteroides uniformis, Bacteroides rodentium, and Parabacteroides merdae) was correlated with three metrics, and their cumulative relative abundance was strongly correlated with the sum of Mayo endoscopic subscore (R = -0.71, p = 2 × 10-9). Five genes (TARP, C10ORF54, ITGAE, TNFSF9, and LCN2) associated with UC pathogenesis were expressed by the 12 key species. The loss of key species may exacerbate UC activity, serving as potential biomarkers.}, }
@article {pmid33912150, year = {2021}, author = {Xu, HM and Huang, HL and Xu, J and He, J and Zhao, C and Peng, Y and Zhao, HL and Huang, WQ and Cao, CY and Zhou, YJ and Zhou, YL and Nie, YQ}, title = {Cross-Talk Between Butyric Acid and Gut Microbiota in Ulcerative Colitis Following Fecal Microbiota Transplantation.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {658292}, pmid = {33912150}, issn = {1664-302X}, abstract = {Fecal microbiota transplantation (FMT) can inhibit the progression of ulcerative colitis (UC). However, how FMT modulates the gut microbiota and which biomarker is valuable for evaluating the efficacy of FMT have not been clarified. This study aimed to determine the changes in the gut microbiota and their relationship with butyric acid following FMT for UC. Fecal microbiota (FM) was isolated from healthy individuals or mice and transplanted into 12 UC patients or colitis mice induced by dextran sulfate sodium (DSS). Their clinical colitis severities were monitored. Their gut microbiota were analyzed by 16S sequencing and bioinformatics. The levels of fecal short-chain fatty acids (SCFAs) from five UC patients with recurrent symptoms after FMT and individual mice were quantified by liquid chromatography-mass spectrometry (LC-MS). The impact of butyric acid on the abundance and diversity of the gut microbiota was tested in vitro. The effect of the combination of butyric acid-producing bacterium and FMT on the clinical responses of 45 UC patients was retrospectively analyzed. Compared with that in the controls, the FMT significantly increased the abundance of butyric acid-producing bacteria and fecal butyric acid levels in UC patients. The FMT significantly increased the α-diversity, changed gut microbial structure, and elevated fecal butyric acid levels in colitis mice. Anaerobic culture with butyrate significantly increased the α-diversity of the gut microbiota from colitis mice and changed their structure. FMT combination with Clostridium butyricum-containing probiotics significantly prolonged the UC remission in the clinic. Therefore, fecal butyric acid level may be a biomarker for evaluating the efficacy of FMT for UC, and addition of butyrate-producing bacteria may prolong the therapeutic effect of FMT on UC by changing the gut microbiota.}, }
@article {pmid33912062, year = {2021}, author = {Schmidt, C and Grunert, PC and Stallmach, A}, title = {An Update for Pharmacologists on New Treatment Options for Inflammatory Bowel Disease: The Clinicians' Perspective.}, journal = {Frontiers in pharmacology}, volume = {12}, number = {}, pages = {655054}, pmid = {33912062}, issn = {1663-9812}, abstract = {The introduction of anti-tumor necrosis factor antibodies resulted in a considerable expansion of the options available for the treatment of inflammatory bowel disease. Unfortunately, approximately one third of treated patients do not respond to these modalities, and drug efficacy may be lost over time. These drugs are also associated with contraindications, adverse events, and intolerance. As such, there is an ongoing need for new therapeutic strategies. Despite several recent advances, including antibodies against pro-inflammatory cytokines and cell adhesion molecules, Janus kinase inhibitors, and modulators of sphingosine-1-phosphate receptors, not all problems associated with IBD have been solved. In this manuscript, we review the current state of development of several new treatment options. Ongoing evaluation will require specific proof of efficacy as well as direct comparisons with established treatments. Results from head-to-head comparisons are needed to provide clinicians with critical information on how to formulate effective therapeutic approaches for each patient.}, }
@article {pmid33910622, year = {2021}, author = {Su, F and Luo, Y and Yu, J and Shi, J and Zhao, Y and Yan, M and Huang, H and Tan, Y}, title = {Tandem fecal microbiota transplantation cycles in an allogeneic hematopoietic stem cell transplant recipient targeting carbapenem-resistant Enterobacteriaceae colonization: a case report and literature review.}, journal = {European journal of medical research}, volume = {26}, number = {1}, pages = {37}, pmid = {33910622}, issn = {2047-783X}, support = {81670169//National Natural Science Foundation of China/ ; 2010KYA075//the Medical Science and Technology Project of Zhejiang Province/ ; }, abstract = {BACKGROUND: Due to limited antibiotic options, carbapenem-resistant Enterobacteriaceae (CRE) infections are associated with high non-relapse mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Also, intestinal CRE colonization is a risk factor for subsequent CRE infection. Several clinical studies have reported successful fecal microbiota transplantation (FMT) for the gut decontamination of a variety of multidrug-resistant bacteria (MDRB), even in immunosuppressed patients. Similarly, other studies have also indicated that multiple FMTs may increase or lead to successful therapeutic outcomes.<br><br>CASE PRESENTATION: We report CRE colonization in an allo-HSCT patient with recurrent CRE infections, and its successful eradication using tandem FMT cycles at 488 days after allo-HSCT. We also performed a comprehensive microbiota analysis. No acute or delayed adverse events (AEs) were observed. The patient remained clinically stable with CRE-negative stool culture at 26-month follow-up. Our analyses also showed some gut microbiota reconstruction. We also reviewed the current literature on decolonization strategies for CRE.<br><br>CONCLUSIONS: CRE colonization led to a high no-relapse mortality after allo-HSCT; however, well-established decolonization strategies are currently lacking. The successful decolonization of this patient suggests that multiple FMT cycles may be potential options for CRE decolonization.}, }
@article {pmid33907321, year = {2021}, author = {Danne, C and Rolhion, N and Sokol, H}, title = {Recipient factors in faecal microbiota transplantation: one stool does not fit all.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {18}, number = {7}, pages = {503-513}, pmid = {33907321}, issn = {1759-5053}, abstract = {Faecal microbiota transplantation (FMT) is a promising therapy for chronic diseases associated with gut microbiota alterations. FMT cures 90% of recurrent Clostridioides difficile infections. However, in complex diseases, such as inflammatory bowel disease, irritable bowel syndrome and metabolic syndrome, its efficacy remains variable. It is accepted that donor selection and sample administration are key determinants of FMT success, yet little is known about the recipient factors that affect it. In this Perspective, we discuss the effects of recipient parameters, such as genetics, immunity, microbiota and lifestyle, on donor microbiota engraftment and clinical efficacy. Emerging evidence supports the possibility that controlling inflammation in the recipient intestine might facilitate engraftment by reducing host immune system pressure on the newly transferred microbiota. Deciphering FMT engraftment rules and developing novel therapeutic strategies are priorities to alleviate the burden of chronic diseases associated with an altered gut microbiota such as inflammatory bowel disease.}, }
@article {pmid33897618, year = {2021}, author = {Huda, MN and Kim, M and Bennett, BJ}, title = {Modulating the Microbiota as a Therapeutic Intervention for Type 2 Diabetes.}, journal = {Frontiers in endocrinology}, volume = {12}, number = {}, pages = {632335}, pmid = {33897618}, issn = {1664-2392}, support = {R01 HL128572/HL/NHLBI NIH HHS/United States ; }, abstract = {Mounting evidence suggested that the gut microbiota has a significant role in the metabolism and disease status of the host. In particular, Type 2 Diabetes (T2D), which has a complex etiology that includes obesity and chronic low-grade inflammation, is modulated by the gut microbiota and microbial metabolites. Current literature supports that unbalanced gut microbial composition (dysbiosis) is a risk factor for T2D. In this review, we critically summarize the recent findings regarding the role of gut microbiota in T2D. Beyond these associative studies, we focus on the causal relationship between microbiota and T2D established using fecal microbiota transplantation (FMT) or probiotic supplementation, and the potential underlying mechanisms such as byproducts of microbial metabolism. These microbial metabolites are small molecules that establish communication between microbiota and host cells. We critically summarize the associations between T2D and microbial metabolites such as short-chain fatty acids (SCFAs) and trimethylamine N-Oxide (TMAO). Additionally, we comment on how host genetic architecture and the epigenome influence the microbial composition and thus how the gut microbiota may explain part of the missing heritability of T2D found by GWAS analysis. We also discuss future directions in this field and how approaches such as FMT, prebiotics, and probiotics supplementation are being considered as potential therapeutics for T2D.}, }
@article {pmid33896875, year = {2021}, author = {Sugita, K and Shima, A and Takahashi, K and Matsuda, Y and Miyajima, M and Hirokawa, M and Kondo, H and Kimura, J and Ishihara, G and Ohmori, K}, title = {Successful outcome after a single endoscopic fecal microbiota transplantation in a Shiba dog with non-responsive enteropathy during the treatment with chlorambucil.}, journal = {The Journal of veterinary medical science}, volume = {83}, number = {6}, pages = {984-989}, pmid = {33896875}, issn = {1347-7439}, mesh = {Animals ; Chlorambucil/therapeutic use ; Diarrhea/veterinary ; *Dog Diseases/drug therapy ; Dogs ; Dysbiosis/veterinary ; Fecal Microbiota Transplantation/veterinary ; Feces ; *Intestinal Diseases/veterinary ; Male ; Treatment Outcome ; }, abstract = {A 7-year 6-month-old, castrated male Shiba dog presented with a 1-month history of lethargy, anorexia, vomiting, and frequent watery diarrhea. Weight loss, hypoalbuminemia, anemia, and leukocytosis were detected at the first visit. The dog was diagnosed with non-responsive enteropathy (NRE) based on clinical and histopathological examinations. Since the dog did not respond to the immunosuppressive drugs, fecal microbiota transplantation (FMT) was performed during the treatment with chlorambucil. A single endoscopic FMT into the cecum and colon drastically recovered clinical signs and clinicopathological abnormalities and corrected dysbiosis in the dog. No recurrence or adverse events were observed. The present case report suggests that FMT, possibly together with chlorambucil, might be a treatment option for NRE in Shiba dogs that have poorer prognosis compared with other dog breeds.}, }
@article {pmid33894059, year = {2021}, author = {Sun, J and Chen, YL and Ding, YC and Zhong, H and Wu, M and Liu, ZH and Ge, LP}, title = {Deposition of resistant bacteria and resistome through FMT in germ-free piglets.}, journal = {Letters in applied microbiology}, volume = {73}, number = {2}, pages = {187-196}, doi = {10.1111/lam.13490}, pmid = {33894059}, issn = {1472-765X}, support = {cstc2019jxjl80019//Chongqing Scientific Research Institute Performance Incentive and Guidance Special Project/ ; 21509(20227)//Chongqing Basic Scientific Research/ ; 20206//the Key R &amp; D Project in Agriculture and Animal Husbandries of Rongchang/ ; }, mesh = {Age Factors ; Animals ; Anti-Bacterial Agents/pharmacology ; Bacteria/*classification/*drug effects ; Biodiversity ; DNA, Bacterial ; Drug Resistance, Multiple, Bacterial/*genetics ; *Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Germ-Free Life ; Interspersed Repetitive Sequences ; Metagenomics ; Swine ; Virulence Factors/*genetics ; }, abstract = {Faecal microbiota transplantation (FMT) has received considerable attention in recent years due to its remarkable efficacy in restoring a normal gut microbiome. Here, we established the groups of post-FMT recipient piglets using germ-free piglets during early life to characterize the colonization of gut microbiota composition and the enrichment of resistance gene acquisition. By metagenomic analysis, we identified 115 bacterial phyla and 2111 bacterial genera that were acquired by the FMT recipients. We found that early-life microbial colonization and the spread of resistomes in recipient piglets were age dependent. A total of 425, 425 and 358 AR genes primarily belonging to 114, 114 and 102 different types were detected in the donors, post-FMT recipients in the FMT-3D group and post-FMT recipients in the FMT-15D group respectively. Genes that encoded tetracycline, macrolide and chloramphenicol resistance proteins were the most dominant AR genes, and the results corresponded with the exposure of antibiotic consumption at farm. Bacteroides, Escherichia, Clostridium, Parabacteroides, Treponema, Lactobacillus and Enterococcus were significantly correlated with the distribution of AR genes. More importantly, the relative abundance of AR genes was positively correlated with the levels of mobile genetic elements. Our results indicate that early-life microbial colonization can persistently shape the gut microbiota and antibiotic resistome.}, }
@article {pmid33888680, year = {2021}, author = {Kong, C and Yan, X and Liu, Y and Huang, L and Zhu, Y and He, J and Gao, R and Kalady, MF and Goel, A and Qin, H and Ma, Y}, title = {Ketogenic diet alleviates colitis by reduction of colonic group 3 innate lymphoid cells through altering gut microbiome.}, journal = {Signal transduction and targeted therapy}, volume = {6}, number = {1}, pages = {154}, pmid = {33888680}, issn = {2059-3635}, abstract = {Accumulating evidence suggests that ketogenic diets (KDs) mediate the rise of circulating ketone bodies and exert a potential anti-inflammatory effect; however, the consequences of this unique diet on colitis remain unknown. We performed a series of systematic studies using a dextran sulfate sodium (DSS) animal model of inflammatory colitis. Animals were fed with a KD, low-carbohydrate diet (LCD), or normal diet (ND). Germ-free mice were utilized in validation experiments. Colon tissues were analyzed by transcriptome sequencing, RT2 profiler PCR array, histopathology, and immunofluorescence. Serum samples were analyzed by metabolic assay kit. Fecal samples were analyzed by 16S rRNA gene sequencing, liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. We observed that KD alleviated colitis by altering the gut microbiota and metabolites in a manner distinct from LCD. Quantitative diet experiments confirmed the unique impact of KD relative to LCD with a reproducible increase in Akkermansia, whereas the opposite was observed for Escherichia/Shigella. After colitis induction, the KD protected intestinal barrier function, and reduced the production of RORγt+CD3- group 3 innate lymphoid cells (ILC3s) and related inflammatory cytokines (IL-17α, IL-18, IL-22, Ccl4). Finally, fecal microbiota transplantation into germ-free mice revealed that the KD- mediated colitis inhibition and ILC3 regulation were dependent on the modification of gut microbiota. Taken together, our study presents a global view of microbiome-metabolomics changes that occur during KD colitis treatment, and identifies the regulation of gut microbiome and ILC3s as novel targets involving in IBD dietary therapy.}, }
@article {pmid33887125, year = {2021}, author = {Bayoumy, AB and Mulder, CJJ and Mol, JJ and Tushuizen, ME}, title = {Gut fermentation syndrome: A systematic review of case reports.}, journal = {United European gastroenterology journal}, volume = {9}, number = {3}, pages = {332-342}, pmid = {33887125}, issn = {2050-6414}, abstract = {BACKGROUND: The gut fermentation syndrome (GFS), also known as the endogenous alcohol fermentation syndrome or auto brewery syndrome, is a rare and underdiagnosed medical condition where consumed carbohydrates are converted to alcohol by the microbiota in the gastrointestinal or urinary tract. The symptoms of GFS can have severe impact on patients' wellbeing and can have social and legal consequences. Unfortunately, not much is reported about GFS. The aim of this systematic review was to assess the evidence for GFS, causal micro-organisms, diagnostics, and possible treatments.<br><br>METHODS: A protocol was developed prior to initiation of the systematic review (PROSPERO 207182). We performed a literature search for clinical studies on 1 September 2020 using PubMed and Embase. We included all clinical studies, including case reports that described the GFS.<br><br>RESULTS: In total, 17 case reports were included, consisting of 20 patients diagnosed with GFS. The species that caused the GFS included Klebsiella pneumoniae, Candida albicans, C. glabrata, Saccharomyces cerevisiae, C. intermedia, C. parapsilosis, and C. kefyr.<br><br>CONCLUSIONS: GFS is a rare but underdiagnosed disease in daily practice. The disease is mostly reported by Saccharomyces and Candida genera, and some cases were previously treated with antibiotics. Studies in Nonalcoholic Fatty Liver disease suggest a bacterial origin of endogenous alcohol-production, which might also be causal micro-organisms in GFS. Current treatments for GFS include antibiotics, antifungal medication, low carbohydrate diet, and probiotics. There might be a potential role of fecal microbiota transplant in the treatment of GFS.}, }
@article {pmid33883174, year = {2021}, author = {de Clercq, NC and van den Ende, T and Prodan, A and Hemke, R and Davids, M and Pedersen, HK and Nielsen, HB and Groen, AK and de Vos, WM and van Laarhoven, HWM and Nieuwdorp, M}, title = {Fecal Microbiota Transplantation from Overweight or Obese Donors in Cachectic Patients with Advanced Gastroesophageal Cancer: A Randomized, Double-blind, Placebo-Controlled, Phase II Study.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {27}, number = {13}, pages = {3784-3792}, doi = {10.1158/1078-0432.CCR-20-4918}, pmid = {33883174}, issn = {1557-3265}, abstract = {PURPOSE: Cachexia is a multifactorial syndrome, associated with poor survival in patients with cancer, and is influenced by the gut microbiota. We investigated the effects of fecal microbiota transplantation (FMT) on cachexia and treatment response in patients with advanced gastroesophageal cancer.<br><br>EXPERIMENTAL DESIGN: In a double-blind randomized placebo-controlled trial performed in the Amsterdam University Medical Center, we assigned 24 cachectic patients with metastatic HER2-negative gastroesophageal cancer to either allogenic FMT (healthy obese donor) or autologous FMT, prior to palliative chemotherapy (capecitabine and oxaliplatin). Primary objective was to assess the effect of allogenic FMT on satiety. Secondary outcomes were other features of cachexia, along with disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and toxicity. Finally, exploratory analyses were performed on the effect of FMT on gut microbiota composition (metagenomic sequencing) and metabolites (untargeted metabolomics).<br><br>RESULTS: Allogenic FMT did not improve any of the cachexia outcomes. Patients in the allogenic group (n = 12) had a higher DCR at 12 weeks (P = 0.035) compared with the autologous group (n = 12), longer median OS of 365 versus 227 days [HR = 0.38; 95% confidence interval (CI), 0.14-1.05; P = 0.057] and PFS of 204 versus 93 days (HR = 0.50; 95% CI, 0.21-1.20; P = 0.092). Patients in the allogenic group showed a significant shift in fecal microbiota composition after FMT (P = 0.010) indicating proper engraftment of the donor microbiota.<br><br>CONCLUSIONS: FMT from a healthy obese donor prior to first-line chemotherapy did not affect cachexia, but may have improved response and survival in patients with metastatic gastroesophageal cancer. These results provide a rational for larger FMT trials.}, }
@article {pmid33883079, year = {2021}, author = {Rinott, E and Youngster, I and Meir, AY and Tsaban, G and Kaplan, A and Zelicha, H and Rubin, E and Koren, O and Shai, I}, title = {Autologous fecal microbiota transplantation can retain the metabolic achievements of dietary interventions.}, journal = {European journal of internal medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ejim.2021.03.038}, pmid = {33883079}, issn = {1879-0828}, abstract = {BACKGROUND: We recently reported that autologous fecal microbiota transplantation (aFMT), derived from the time of maximal weight-loss and administrated in the regain-phase, might preserve weight loss and glycemic control in moderately obese subjects, and is associated with specific microbiome signatures. Here, we sought to explore the global effect of aFMT on adipokines, inflammatory markers and blood cholesterol and on the overall gut microbiome preservation.<br><br>METHODS: In the DIRECT-PLUS weight-loss trial, abdominally obese participants were randomized to three distinct weight-loss diets. Following the expected weight loss phase (0-6 m), 90 participants were randomized to receive their personal frozen fecal microbiota or placebo oral capsules (ten 1 g-capsules over ten sessions-total=100 g) during the expected weight regain phase (8-14 m).<br><br>RESULTS: Of the 90 participants (age=52 yr; 0-6 m weight loss=-8.3 kg), 95.6% ingested at least 80/100 oral aFMT/placebo capsules over 6 months. Overall, the gut microbiome community structure was associated with plasma levels of leptin, cholesterol and interleukin-6 at baseline and after 6 m, whereas 6 m (weight loss phase) changes in specific microbiome species associated with the dynamic of leptin and inflammatory biomarkers. Following the 8-14 m aFMT administration phase, aFMT maintained decreased levels of leptin (ΔaFMT=-3.54 ng/mL vs. Δplacebo=-0.82 ng/mL;P = 0.04), C-reactive-protein (ΔaFMT=-1.45 mg/L vs. Δplacebo=-0.66 mg/L;P = 0.009), Interleukin-6 (ΔaFMT=-0.03pg/mL vs. Δplacebo=1.11pg/mL;P = 0.03) and total cholesterol (ΔaFMT=2.2 mg/dl vs. Δplacebo=13.1 mg/dl;P = 0.04) achieved in the weight loss phase. Overall, aFMT induced a significant preservatory effect on personal gut microbiome global composition (P = 0.03;Jensen-Shannon distance), as compared to placebo.<br><br>CONCLUSIONS: aFMT treatment in the regain phase might retain weight-loss induced metabolic benefits. These findings may suggest a novel aFMT treatment approach for personal metabolic attainment preservation.}, }
@article {pmid33882637, year = {2021}, author = {Van Lier, YF and Van den Brink, MRM and Hazenberg, MD and Markey, KA}, title = {The post-hematopoietic cell transplantation microbiome: relationships with transplant outcome and potential therapeutic targets.}, journal = {Haematologica}, volume = {106}, number = {8}, pages = {2042-2053}, pmid = {33882637}, issn = {1592-8721}, abstract = {Microbiota injury occurs in many patients undergoing allogeneic hematopoietic cell transplantation, likely as a consequence of conditioning regimens involving chemo- and radiotherapy, the widespread use of both prophylactic and therapeutic antibiotics, and profound dietary changes during the peri-transplant period. Peri-transplant dysbiosis is characterized by a decrease in bacterial diversity, loss of commensal bacteria and single-taxon domination (e.g., with Enterococcal strains). Clinically, deviation of the post-transplant microbiota from a normal, high-diversity, healthy state has been associated with increased risk of bacteremia, development of graft-versus-host disease and decreases in overall survival. A number of recent clinical trials have attempted to target the microbiota in allogeneic hematopoietic cell transplantation patients via dietary interventions, selection of therapeutic antibiotics, administration of pre- or pro-biotics, or by performing fecal microbiota transplantation. These strategies have yielded promising results but the mechanisms by which these interventions influence transplant-related complications remain largely unknown. In this review we summarize the current approaches to targeting the microbiota, discuss potential underlying mechanisms and highlight the key outstanding areas that require further investigation in order to advance microbiota- targeting therapies.}, }
@article {pmid33881598, year = {2021}, author = {Metta, V and Leta, V and Mrudula, KR and Prashanth, LK and Goyal, V and Borgohain, R and Chung-Faye, G and Chaudhuri, KR}, title = {Gastrointestinal dysfunction in Parkinson's disease: molecular pathology and implications of gut microbiome, probiotics, and fecal microbiota transplantation.}, journal = {Journal of neurology}, volume = {}, number = {}, pages = {}, pmid = {33881598}, issn = {1432-1459}, abstract = {Gastrointestinal symptoms and gut dysbiosis may occur before the onset of motor symptoms in Parkinson's disease (PD). Prediagnostic and prodromal features, such as constipation and α-synuclein pathology, can be detected several years before the clinical diagnosis of PD and have the potential to develop as early PD biomarkers. Environmental toxins and gut dysbiosis may trigger oxidative stress and mucosal inflammation, and initiate α-synuclein accumulation in the enteric nervous system, early in PD. Chronic gut inflammation can lead to a leaky gut and systemic inflammation, neuro inflammation, and neuro degeneration via gut-vagus-brain signaling or through blood-brain barrier permeability. Concepts regarding the gut-brain signaling in PD pathogenesis are changing rapidly and more investigation is required. The gut microbiota interacts with the human body by modulating the enteric and central nervous systems, and immune activity. Understanding the immune responses between gut microbiota and human body might help in elucidating the PD pathogenesis. As changes in gut microbiota composition might be associated with different clinical phenotypes of PD, gut microbiota-modulating interventions, such as probiotics and fecal microbiota transplantation (FMT), have the potential to restore the gut dysbiosis, reduce inflammation, and possibly modulate the clinical PD phenotype.}, }
@article {pmid33880565, year = {2021}, author = {Golob, JL and Rao, K}, title = {Signal Versus Noise: How to Analyze the Microbiome and Make Progress on Antimicrobial Resistance.}, journal = {The Journal of infectious diseases}, volume = {223}, number = {Supplement_3}, pages = {S214-S221}, pmid = {33880565}, issn = {1537-6613}, support = {R01 HS027431/HS/AHRQ HHS/United States ; U01 AI124255/AI/NIAID NIH HHS/United States ; }, abstract = {Antimicrobial resistance has become a worldwide medical challenge [1], so impactful that vancomycin-resistant Enterococcus (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) have entered the common vernacular. We have attempted to reduce the selective pressure through antimicrobial stewardship, curtail the spread by identifying and isolating carriers and individuals with symptomatic infection, and treat antibiotic-resistant organisms (AROs) by developing novel antimicrobials. Despite these extraordinary measures, the challenge of AROs continues to grow. The gut microbiome, the ecosystem of microbes (ie, the microbiota) and metabolites present upon and within all humans, is an emerging target for both the risk for colonization and defense against infection with AROs. Here, informed from experiences and successes with understanding the role of the microbiome in mediating risk of Clostridioides difficile infection (CDI), we (1) review our understanding of the risk from ARO acquisition; (2) review our current understanding of the gut microbiome's ability to resist colonization with AROs; (3) describe how experimental model systems can test these initial, global insights to arrive at more granular, mechanistic ones; and (4) suggest a path forward to make further progress in the field.}, }
@article {pmid33879696, year = {2021}, author = {Wang, N and Yao, W and Ma, R and Ren, F}, title = {The efficacy of a multistrain probiotic on cognitive function and risk of falls in patients with cirrhosis: A protocol for systematic review and meta-analysis.}, journal = {Medicine}, volume = {100}, number = {16}, pages = {e25535}, doi = {10.1097/MD.0000000000025535}, pmid = {33879696}, issn = {1536-5964}, support = {2015GSF121033//Shandong province key research and development project/ ; }, mesh = {Accidental Falls/*prevention &amp; control ; Cognition ; Cognitive Dysfunction/microbiology/*prevention &amp; control ; Female ; Humans ; Liver Cirrhosis/microbiology/*psychology/*therapy ; Male ; Meta-Analysis as Topic ; Probiotics/*therapeutic use ; Randomized Controlled Trials as Topic ; Research Design ; Risk Factors ; Systematic Reviews as Topic ; Treatment Outcome ; }, abstract = {OBJECTIVE: The effect of probiotics on cognitive function and the risk of falling in cirrhosis patients have not been previously evaluated. We perform this protocol for systematic review and meta-analysis to evaluate the effect of a multistrain probiotic on cognitive function and the risk of falls in patients with cirrhosis.<br><br>METHODS: An all-round retrieval will be performed in 5 electronic journal databases from their inception to March 2021, which comprise Medline, Pubmed, Embase, ScienceDirect, and the Cochrane Library by 2 independent reviewers. Data extraction was performed independently, and any conflict was resolved before final analysis. Only randomized clinical trials were included in this study. The main endpoints were cognitive function and risk of falls, and the secondary endpoints were fall incidence, health-related quality of life (HRQOL), systemic inflammatory response, gut barrier, bacterial translocation, and fecal microbiota. The risk of bias assessment of the included studies was performed by 2 authors independently using the tool recommended in the Cochrane Handbook for Systematic Reviews of Interventions.<br><br>RESULTS: We hypothesized that the multistrain probiotic improved cognitive function, risk of falls, and inflammatory response in patients with cirrhosis and cognitive dysfunction.<br><br>CONCLUSION: This study expects to provide credible and scientific clinical evidence for the efficacy and safety of a multistrain probiotic on cognitive function and the risk of falls in patients with cirrhosis.<br><br>OSF REGISTRATION NUMBER: 10.17605/OSF.IO/JKMTP.}, }
@article {pmid33878733, year = {2021}, author = {Zhang, J and Chen, Z and Yu, H and Lu, Y and Yu, W and Miao, M and Shi, H}, title = {Anti-aging effects of a functional food via the action of gut microbiota and metabolites in aging mice.}, journal = {Aging}, volume = {13}, number = {13}, pages = {17880-17900}, pmid = {33878733}, issn = {1945-4589}, mesh = {Aging/genetics/*physiology ; Animals ; Antioxidants/metabolism ; Body Weight ; CA1 Region, Hippocampal/growth &amp; development/metabolism ; Diet ; Eating ; Feces/microbiology ; *Functional Food ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*metabolism/*microbiology ; Lymphocyte Count ; Male ; Mice ; Mice, Inbred Strains ; Nervous System Physiological Phenomena ; }, abstract = {Wushen (WS) is a mixed food containing 55 natural products that is beneficial to human health. This study aimed to reveal the preventive effect of WS on aging via a combined analysis of gut microbiome and metabolome. Senescence-accelerated mouse prone 8 (SAMP8) mice were used as aging model and senescence-accelerated mouse resistant 1 (SAMR1) mice as control. The mice were fed four diet types; control diet (for SAMR1 mice), standard diet (for SAMP8 mice, as SD group), WS diet, and fecal microbiota transplantation (FMT; transplanted from aging-WS mice). Our results showed that the weight, food intake, neurological function, and general physical conditions significantly improved in WS-fed mice compared to those fed with SD. The CA1 hippocampal region in WS-fed aged mice showed fewer shriveled neurons and increased neuronal layers compared to that of the SD group. WS-fed mice showed a decrease in malondialdehyde and an increase in superoxide dismutase levels in the brain; additionally, IL-6 and TNF-α levels significantly decreased, whereas IL-2 levels and the proportion of lymphocytes, CD3+CD8+ T, and CD4+IFNγ+T cells increased in WS-fed mice. After fed with WS, the abundance of Ruminococcus and Butyrivibrio markedly increased, whereas Lachnoclostridium and Ruminiclostridium significantly decreased in the aging mice. In addition, 887 differentially expressed metabolites were identified in fecal samples, among these, Butyrivibrio was positively correlated with D-glucuronic acid and Ruminococcus was positively associated with 5-acetamidovalerate. These findings provide mechanistic insight into the impact of WS on aging, and WS may be a valuable diet for preventing aging.}, }
@article {pmid33872339, year = {2021}, author = {Gal, A and Barko, PC and Biggs, PJ and Gedye, KR and Midwinter, AC and Williams, DA and Burchell, RK and Pazzi, P}, title = {One dog's waste is another dog's wealth: A pilot study of fecal microbiota transplantation in dogs with acute hemorrhagic diarrhea syndrome.}, journal = {PloS one}, volume = {16}, number = {4}, pages = {e0250344}, pmid = {33872339}, issn = {1932-6203}, abstract = {Canine acute hemorrhagic diarrhea syndrome (AHDS) has been associated in some studies with Clostridioides perfringens overgrowth and toxin-mediated necrosis of the intestinal mucosa. We aimed to determine the effect of a single fecal microbiota transplantation (FMT) on clinical scores and fecal microbiomes of 1 and 7 dogs with AHDS from New Zealand and South Africa. We hypothesized that FMT would improve AHDS clinical scores and increase microbiota alpha-diversity and short-chain fatty acid (SCFA)-producing microbial communities' abundances in dogs with AHDS after FMT. We sequenced the V3-V4 region of the 16S-rRNA gene in the feces of AHDS FMT-recipients and sham-treated control dogs, and their healthy donors at admission, discharge, and 30 days post-discharge. There were no significant differences in median AHDS clinical scores between FMT-recipients and sham-treated controls at admission or discharge (P = 0.22, P = 0.41). At admission, the Shannon diversity index (SDI) was lower in AHDS dogs than healthy donors (P = 0.002). The SDI did not change from admission to 30 days in sham-treated dogs yet increased in FMT-recipients from admission to discharge (P = 0.04) to levels not different than donors (P = 0.33) but significantly higher than sham-treated controls (P = 0.002). At 30 days, the SDI did not differ between FMT recipients, sham-treated controls, and donors (P = 0.88). Principal coordinate analysis of the Bray-Curtis index separated post-FMT and donor dogs from pre-FMT and sham-treated dogs (P = 0.009) because of increased SCFA-producing genera's abundances after FMT. A single co-abundance subnetwork contained many of the same OTUs found to be differentially abundant in FMT-recipients, and the abundance of this module was increased in FMT-recipients at discharge and 30 days, compared to sham-treated controls. We conclude in this small pilot study FMT did not have any clinical benefit. A single FMT procedure has the potential to increase bacterial communities of SCFA-producing genera important for intestinal health up to 30 days post-FMT.}, }
@article {pmid33869077, year = {2021}, author = {Gao, Y and Zhang, J and Xiao, X and Ren, Y and Yan, X and Yue, J and Wang, T and Wu, Z and Lv, Y and Wu, R}, title = {The Role of Gut Microbiota in Duodenal-Jejunal Bypass Surgery-Induced Improvement of Hepatic Steatosis in HFD-Fed Rats.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {640448}, pmid = {33869077}, issn = {2235-2988}, mesh = {Animals ; *Diet, High-Fat ; Duodenum ; *Gastrointestinal Microbiome ; Jejunum ; Male ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Bariatric surgery including duodenal-jejunal bypass surgery (DJB) improves insulin sensitivity and reduces obesity-associated inflammation. However, the underlying mechanism for such an improvement is still incompletely understood. Our objective was to investigate the role of the gut microbiota in DJB-associated improvement of hepatic steatosis in high fat diet (HFD)-fed rats. To study this, hepatic steatosis was induced in male adult Sprague-Dawley rats by feeding them with a 60% HFD. At 8 weeks after HFD feeding, the rats were subjected to either DJB or sham operation. HFD was resumed 1 week after the surgery for 3 more weeks. In additional groups of animals, feces were collected from HFD-DJB rats at 2 weeks after DJB. These feces were then transplanted to HFD-fed rats without DJB at 8 weeks after HFD feeding. Hepatic steatosis and fecal microbiota were analyzed at 4 weeks after surgery or fecal transplantation. Our results showed that DJB alleviated hepatic steatosis in HFD-fed rats. Fecal microbiota analysis showed that HFD-fed and standard diet-fed rats clustered differently. DJB induced substantial compositional changes in the gut microbiota. The fecal microbiota of HFD-fed rats received fecal transplant from DJB rats overlapped with that of HFD-DJB rats. Treatment of rats with HFD-induced liver lesions by fecal transplant from DJB-operated HFD-fed rats also attenuated hepatic steatosis. Thus, alterations in the gut microbiota after DJB surgery are sufficient to attenuate hepatic steatosis in HFD-fed rats. Targeting the gut microbiota could be a promising approach for preventing or treating human NAFLD.}, }
@article {pmid33864273, year = {2021}, author = {Pomares Bascuñana, RÁ and Veses, V and Sheth, CC}, title = {Effectiveness of fecal microbiota transplant for the treatment of Clostridioides difficile diarrhea: a systematic review and meta-analysis.}, journal = {Letters in applied microbiology}, volume = {73}, number = {2}, pages = {149-158}, doi = {10.1111/lam.13486}, pmid = {33864273}, issn = {1472-765X}, mesh = {Administration, Oral ; Capsules/administration &amp; dosage ; Clostridioides difficile ; Clostridium Infections/microbiology/*therapy ; Diarrhea/microbiology/*therapy ; Enema ; Fecal Microbiota Transplantation/adverse effects/*methods ; Gastrointestinal Microbiome ; Humans ; Treatment Outcome ; }, abstract = {Clostridioides difficile is a major cause of health-care related infections and antibiotic-associated diarrhea. High recurrence rates following antibiotic treatment, along with the emergence of hypervirulent and multidrug resistant ribotypes makes essential the development of safe, effective, novel therapies for the treatment of C. difficile infections. The primary outcome evaluated in this meta-analysis was the effectiveness of fecal microbiota transplantation (FMT). Secondary outcomes were the proportion of patients suffering adverse effects along with the most effective administration route. The mean treatment effectiveness was 82% (95% CI: 75-89). Overall, patients receiving FMT via colonoscopy experienced more adverse effects than patients whom received enema, or oral capsules (71·6% vs 40·2%, and 35·3% respectively). Comparing administration of FMT by colonoscopy versus enema resulted in a Hedges' g of -0·74 (95% CI of -0·9 to -0·58), indicating a slight advantage in favor of colonoscopy. The comparison between colonoscopy and capsule returned a Hedges' g of 0·44 (95% CI of 0·20-0·69), indicating that delivery of the FMT by capsule was statistically significantly more effective. FMT provides an effective and safe treatment for C. difficile diarrhea. Further research into the efficacy of different preparation protocols is needed.}, }
@article {pmid33864057, year = {2021}, author = {Zipkin, M}, title = {Fecal microbiota potentiate checkpoint inhibitors, unleash microbiome startups.}, journal = {Nature biotechnology}, volume = {39}, number = {5}, pages = {529-532}, doi = {10.1038/d41587-021-00002-w}, pmid = {33864057}, issn = {1546-1696}, mesh = {*Fecal Microbiota Transplantation ; Feces/*microbiology ; Humans ; Immune Checkpoint Inhibitors/*therapeutic use ; Microbiota/genetics ; Neoplasms/microbiology/*therapy ; }, }
@article {pmid33863898, year = {2021}, author = {Li, X and Su, C and Jiang, Z and Yang, Y and Zhang, Y and Yang, M and Zhang, X and Du, Y and Zhang, J and Wang, L and Jiang, J and Hong, B}, title = {Berberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-N-oxide production via manipulating the gut microbiome.}, journal = {NPJ biofilms and microbiomes}, volume = {7}, number = {1}, pages = {36}, pmid = {33863898}, issn = {2055-5008}, mesh = {Animals ; Atherosclerosis/*etiology/*metabolism/pathology ; Berberine/*pharmacology ; Choline/*adverse effects ; Diet ; Disease Models, Animal ; Disease Susceptibility ; Dysbiosis ; Gastrointestinal Microbiome/*drug effects ; Methylamines/*metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout, ApoE ; }, abstract = {Trimethylamine-N-oxide (TMAO), a derivative from the gut microbiota metabolite trimethylamine (TMA), has been identified to be an independent risk factor for promoting atherosclerosis. Evidences suggest that berberine (BBR) could be used to treat obesity, diabetes and atherosclerosis, however, its mechanism is not clear mainly because of its poor oral bioavailability. Here, we show that BBR attenuated TMA/TMAO production in the C57BL/6J and ApoE KO mice fed with choline-supplemented chow diet, and mitigated atherosclerotic lesion areas in ApoE KO mice. Inhibition of TMA/TMAO production by BBR-modulated gut microbiota was proved by a single-dose administration of d9-choline in vivo. Metagenomic analysis of cecal contents demonstrated that BBR altered gut microbiota composition, microbiome functionality, and cutC/cntA gene abundance. Furthermore, BBR was shown to inhibit choline-to-TMA conversion in TMA-producing bacteria in vitro and in gut microbial consortium from fecal samples of choline-fed mice and human volunteers, and the result was confirmed by transplantation of TMA-producing bacteria in mice. These results offer new insights into the mechanisms responsible for the anti-atherosclerosis effects of BBR, which inhibits commensal microbial TMA production via gut microbiota remodeling.}, }
@article {pmid33863483, year = {2021}, author = {Albuhairi, S and Rachid, R}, title = {Biologics and Novel Therapies for Food Allergy.}, journal = {Immunology and allergy clinics of North America}, volume = {41}, number = {2}, pages = {271-283}, doi = {10.1016/j.iac.2021.01.002}, pmid = {33863483}, issn = {1557-8607}, abstract = {Food allergy is a significant public health burden affecting around 10% of adults and 8% of children. Although the first peanut oral immunotherapy product received Food and Drug Administration approval in 2020, there is still an unmet need for more effective therapeutic options that minimize the risk of anaphylaxis, nutritional deficiencies, and patient's quality of life. Biologics are promising modalities, as they may improve compliance, target multiple food allergies, and treat other concomitant atopic diseases. Although omalizumab has been evaluated extensively, most biologics are more novel and have broader immunologic impact. Careful evaluation of their safety profile should therefore be conducted.}, }
@article {pmid33856024, year = {2021}, author = {Wang, Q and Luo, Y and Chaudhuri, KR and Reynolds, R and Tan, EK and Pettersson, S}, title = {The role of gut dysbiosis in Parkinson's disease: mechanistic insights andtherapeutic options.}, journal = {Brain : a journal of neurology}, volume = {}, number = {}, pages = {}, doi = {10.1093/brain/awab156}, pmid = {33856024}, issn = {1460-2156}, abstract = {Parkinson's disease is a common neurodegenerative disease in which gastrointestinal symptoms may appear prior to motor symptoms. The gut microbiota of patients with Parkinson's disease shows unique changes, which may be used as early biomarkers of disease. Alteration in gut microbiota composition may be related to the cause or effect of motor or non-motor symptoms, but the specific pathogenic mechanisms are unclear. The gut microbiota and its metabolites have been suggested to be involved in the pathogenesis of Parkinson's disease by regulating neuroinflammation, barrier function and neurotransmitter activity. There is bidirectional communication between the enteric nervous system and the central nervous system, and the microbiota-gut-brain axis may provide a pathway for the transmission of α-synuclein. We highlight recent discoveries and alterations of the gut microbiota in Parkinson's disease, and highlight current mechanistic insights on the microbiota-gut-brain axis in disease pathophysiology. We discuss the interactions between production and transmission of α-synuclein and gut inflammation and neuroinflammation. In addition, we also draw attention to diet modification, use of probiotics and prebiotics and fecal microbiota transplantation as potential therapeutic approaches that may lead to a new treatment paradigm for Parkinson's disease.}, }
@article {pmid33852207, year = {2021}, author = {Ballif, A and Gerber, S and Carrez, L and Audry, M and Sadeghipour, F and Mitouassiwou, A and Croxatto, A and Opota, O and Prod'hom, G and Henchoz, S and Schoepfer, A and Cavassini, M and Galpérine, T}, title = {[Fecal microbiota transplantation: from the evidence to the realty of the field].}, journal = {Revue medicale suisse}, volume = {17}, number = {734}, pages = {726-731}, pmid = {33852207}, issn = {1660-9379}, mesh = {*Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; Recurrence ; Treatment Outcome ; }, abstract = {In clinical practice, fecal microbiota transplantation (FMT) has been established as an unparalleled therapy to date for multiple recurrent Clostridioides difficile infections (CDI). The implementation of the FMT in practice requires a significant investment to meet legal, security and financial requirements. Research on the microbiota is booming and multiple investigations on FMT in indications other than CDI are ongoing.}, }
@article {pmid33851215, year = {2021}, author = {Cappetto, CM}, title = {Successful use of early, repeat fecal microbiota transplantation for initial treatment of severe, refractory Clostridioides difficile colitis.}, journal = {American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists}, volume = {78}, number = {15}, pages = {1374-1381}, doi = {10.1093/ajhp/zxab161}, pmid = {33851215}, issn = {1535-2900}, abstract = {PURPOSE: There is a paucity of literature surrounding the use of early fecal microbiota transplantation (FMT) for patients presenting with an initial episode of severe, refractory Clostridioides difficile infection (CDI). Information on optimal antibiotic dosing and therapy duration surrounding FMT during an acute, initial episode of CDI is also limited. Described here is a case of successful treatment of CDI after 4 FMTs during an acute, initial episode of severe, refractory Clostridioides difficile colitis.<br><br>SUMMARY: A 69-year-old community-dwelling, Caucasian male presented after 48 hours of vomiting and diarrhea. A stool sample was collected and resulted positive for Clostridioides difficile by both polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). The patient was treated with several days of oral and rectal vancomycin therapy in addition to intravenous metronidazole, but those treatments failed. His clinical and nutrition status deteriorated over the course of several days until salvage therapy was ordered, with administration of 1 inpatient nasogastric FMT and 1 inpatient colonoscopic FMT followed by outpatient colonoscopic FMTs on 2 consecutive days within 2 weeks of hospital discharge.<br><br>CONCLUSION: This case suggests a role for early, repeat FMT during an initial presentation of a severe Clostridioides difficile colitis episode refractory to pharmacologic antimicrobial therapy. It also adds to emerging literature regarding the timing of antibiotic cessation surrounding FMT.}, }
@article {pmid33847139, year = {2021}, author = {Khanna, S and Kraft, CS}, title = {The interplay of SARS-CoV-2 and Clostridioides difficile infection.}, journal = {Future microbiology}, volume = {16}, number = {}, pages = {439-443}, doi = {10.2217/fmb-2020-0275}, pmid = {33847139}, issn = {1746-0921}, mesh = {*COVID-19/epidemiology/transmission ; Clostridioides difficile/isolation &amp; purification ; *Clostridium Infections/diagnosis/epidemiology/therapy ; *Coinfection/diagnosis/epidemiology ; Cross Infection/*prevention &amp; control ; Fecal Microbiota Transplantation ; *Feces/microbiology/virology ; Humans ; Infection Control ; Pandemics/*prevention &amp; control ; SARS-CoV-2/isolation &amp; purification ; }, abstract = {The COVID-19 pandemic has changed the way we practice medicine and lead our lives. In addition to pulmonary symptoms; COVID-19 as a syndrome has multisystemic involvement including frequent gastrointestinal symptoms such as diarrhea. Due to microbiome alterations with COVID-19 and frequent antibiotic exposure, COVID-19 can be complicated by Clostridioides difficile infection. Co-infection with these two can be associated with a high risk of complications. Infection control measures in hospitals is enhanced due to the COVID-19 pandemic which in turn appears to reduce the incidence of hospital-acquired infections such as C. difficile infection. Another implication of COVID-19 and its potential transmissibility by stool is microbiome-based therapies. Potential stool donors should be screened COVID-19 symptoms and be tested for COVID-19.}, }
@article {pmid33844988, year = {2021}, author = {Monaghan, TM and Seekatz, AM and Markham, NO and Yau, TO and Hatziapostolou, M and Jilani, T and Christodoulou, N and Roach, B and Birli, E and Pomenya, O and Louie, T and Lacy, DB and Kim, P and Lee, C and Kao, D and Polytarchou, C}, title = {Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection Associates With Functional Alterations in Circulating microRNAs.}, journal = {Gastroenterology}, volume = {161}, number = {1}, pages = {255-270.e4}, doi = {10.1053/j.gastro.2021.03.050}, pmid = {33844988}, issn = {1528-0012}, support = {I01 BX002943/BX/BLRD VA/United States ; R37 AI095755/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND AND AIMS: The molecular mechanisms underlying successful fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (rCDI) remain poorly understood. The primary objective of this study was to characterize alterations in microRNAs (miRs) following FMT for rCDI.<br><br>METHODS: Sera from 2 prospective multicenter randomized controlled trials were analyzed for miRNA levels with the use of the Nanostring nCounter platform and quantitative reverse-transcription (RT) polymerase chain reaction (PCR). In addition, rCDI-FMT and toxin-treated animals and ex vivo human colonoids were used to compare intestinal tissue and circulating miRs. miR inflammatory gene targets in colonic epithelial and peripheral blood mononuclear cells were evaluated by quantitative PCR (qPCR) and 3'UTR reporter assays. Colonic epithelial cells were used for mechanistic, cytoskeleton, cell growth, and apoptosis studies.<br><br>RESULTS: miRNA profiling revealed up-regulation of 64 circulating miRs 4 and 12 weeks after FMT compared with screening, of which the top 6 were validated in the discovery cohort by means of RT-qPCR. In a murine model of relapsing-CDI, RT-qPCR analyses of sera and cecal RNA extracts demonstrated suppression of these miRs, an effect reversed by FMT. In mouse colon and human colonoids, C difficile toxin B (TcdB) mediated the suppressive effects of CDI on miRs. CDI dysregulated DROSHA, an effect reversed by FMT. Correlation analyses, qPCR ,and 3'UTR reporter assays revealed that miR-23a, miR-150, miR-26b, and miR-28 target directly the 3'UTRs of IL12B, IL18, FGF21, and TNFRSF9, respectively. miR-23a and miR-150 demonstrated cytoprotective effects against TcdB.<br><br>CONCLUSIONS: These results provide novel and provocative evidence that modulation of the gut microbiome via FMT induces alterations in circulating and intestinal tissue miRs. These findings contribute to a greater understanding of the molecular mechanisms underlying FMT and identify new potential targets for therapeutic intervention in rCDI.}, }
@article {pmid33840331, year = {2021}, author = {Madsen, M and Kimer, N and Bendtsen, F and Petersen, AM}, title = {Fecal microbiota transplantation in hepatic encephalopathy: a systematic review.}, journal = {Scandinavian journal of gastroenterology}, volume = {56}, number = {5}, pages = {560-569}, doi = {10.1080/00365521.2021.1899277}, pmid = {33840331}, issn = {1502-7708}, abstract = {Hepatic encephalopathy (HE) is a reversible neurocognitive dysfunction that ranges in severity from subclinical alterations to coma. Patients with chronic liver disease are predisposed to HE due to metabolic failure and portosystemic shunting of toxins, of which ammonia is believed to be the main toxic chemical. Fecal microbiota transplantation (FMT) may reduce ammonia synthesis by altering the gut microbiota composition to a taxon low in urease, diminish uptake of ammonia by reestablishing the integrity of the intestinal barrier and increase ammonia clearance by improving liver function. In this systematic review, we summarize the insights of the current literature examining FMT as a treatment for HE.PubMed and EMBASE were searched on 08 February 2021 using the MeSH terms 'fecal microbiota transplantation &amp; hepatic encephalopathy' and the abbreviations 'FMT &amp; HE'.Eight studies fulfilled our inclusion criteria, comprising two randomized clinical trials, three case reports and three rodent studies. Thirty-nine patients with HE were treated with FMT. Thirty-nine rodents received FMT in laboratory tests. FMT improved neurocognitive test results in four human studies and two rodent studies. Microbiota originating from donors was found in human recipients one year post-FMT. Readmission of patients was lower after treatment with FMT compared to standard of care.FMT may improve neurocognitive function and reduce serious adverse events in patients with HE, but the studies conducted so far have been small and their long-term follow-up is limited. Large-scale, randomized and controlled trials are needed to validate and help standardize the clinical application of FMT in cases of HE.}, }
@article {pmid33836037, year = {2021}, author = {Björkqvist, O and Rangel, I and Serrander, L and Magnusson, C and Halfvarson, J and Norén, T and Bergman-Jungeström, M}, title = {Faecalibacterium prausnitzii increases following fecal microbiota transplantation in recurrent Clostridioides difficile infection.}, journal = {PloS one}, volume = {16}, number = {4}, pages = {e0249861}, pmid = {33836037}, issn = {1932-6203}, abstract = {OBJECTIVE: Fecal microbiota transplantation (FMT) is a highly effective treatment for Clostridioides difficile infection (CDI). However, the fecal transplant's causal components translating into clearance of the CDI are yet to be identified. The commensal bacteria Faecalibacterium prausnitzii may be of great interest in this context, since it is one of the most common species of the healthy gut microbiota and produces metabolites with anti-inflammatory properties. Although there is mounting evidence that F. prausnitzii is an important regulator of intestinal homeostasis, data about its role in CDI and FMT are relatively scarce.<br><br>METHODS: Stool samples from patients with recurrent CDI were collected to investigate the relative abundance of F. prausnitzii before and after FMT. Twenty-one patients provided fecal samples before the FMT procedure, at 2 weeks post-FMT, and at 2-4 months post-FMT. The relative abundance of F. prausnitzii was determined using quantitative polymerase chain reaction.<br><br>RESULTS: The abundance of F. prausnitzii was elevated in samples (N = 9) from donors compared to pre-FMT samples (N = 15) from patients (adjusted P<0.001). No significant difference in the abundance of F. prausnitzii between responders (N = 11) and non-responders (N = 4) was found before FMT (P = 0.85). In patients with CDI, the abundance of F. prausnitzii significantly increased in the 2 weeks post-FMT samples (N = 14) compared to the pre-FMT samples (N = 15, adjusted P<0.001). The increase persisted 2-4 months post-FMT (N = 15) compared to pre-FMT samples (N = 15) (adjusted P<0.001).<br><br>CONCLUSIONS: FMT increases the relative abundance of F. prausnitzii in patients with recurrent CDI, and this microbial shift remains several months later. The baseline abundance of F. prausnitzii in donors or recipients was not associated with future treatment response, although a true predictive capacity cannot be excluded because of the limited sample size. Further studies are needed to discern whether F. prausnitzii plays an active role in the resolution of CDI.}, }
@article {pmid33834162, year = {2020}, author = {Grigoryan, Z and Shen, MJ and Twardus, SW and Beuttler, MM and Chen, LA and Bateman-House, A}, title = {Fecal microbiota transplantation: Uses, questions, and ethics.}, journal = {Medicine in microecology}, volume = {6}, number = {}, pages = {}, pmid = {33834162}, issn = {2590-0978}, support = {K23 DK119544/DK/NIDDK NIH HHS/United States ; }, abstract = {Fecal microbiota transplantation (FMT) has rapidly grown in notoriety and popularity worldwide as a treatment for both recurrent and refractory C. difficile infection (CDI), as well as for a myriad of other indications, with varying levels of evidence to justify its use. At present, FMT use in the U.S. has not received marketing approval from the U.S. Food and Drug Administration (FDA), but is permitted under "enforcement discretion" for CDI not responding to standard therapy. Meanwhile, the rising interest in the gut microbiome throughout mainstream media has paved the way for "do-it-yourself" (DIY) adaptations of the procedure. This access and unregulated use, often outside any clinical supervision, has quickly outpaced the medical community's research and regulatory efforts. While some studies have been able to demonstrate the success of FMT in treating conditions other than CDI-studies on ulcerative colitis have been particularly promising-little is still known about the treatmen's mechanism of action or long-term side effects. Likewise, screening of donor stool is in its early stages in terms of protocol standardization. In this paper, we explore the regulatory and ethical concerns that arise from the need to balance access to a nascent but promising innovative treatment with the need for research into its efficacy, risk profile, and long-term impact.}, }
@article {pmid33832129, year = {2021}, author = {Fang, S and Wu, S and Ji, L and Fan, Y and Wang, X and Yang, K}, title = {The combined therapy of fecal microbiota transplantation and laxatives for functional constipation in adults: A systematic review and meta-analysis of randomized controlled trials.}, journal = {Medicine}, volume = {100}, number = {14}, pages = {e25390}, pmid = {33832129}, issn = {1536-5964}, support = {112123A12201/001/002//Graduate Science Research Fund of Zhejiang Chinese Medical University/ ; }, mesh = {Adult ; Aged ; Case-Control Studies ; China/epidemiology ; Combined Modality Therapy/adverse effects/*methods ; Constipation/*physiopathology/psychology/*therapy ; Data Management ; Fecal Microbiota Transplantation/adverse effects/*methods ; Female ; Humans ; Laxatives/adverse effects/*therapeutic use ; Male ; Middle Aged ; Quality of Life ; Randomized Controlled Trials as Topic ; Safety ; Treatment Outcome ; }, abstract = {OBJECTIVE: Functional constipation is a prevalent, burdensome gastrointestinal disorder whose treatment remains challenging. Combined therapy uniting multiple treatments may be promising. Fecal microbiota transplantation (FMT) which tends to be an etiological treatment has been increasingly investigated in its management. Meanwhile, laxatives are widely used to relieve constipation temporarily, but their overall efficacy is poor. Therefore, we performed meta-analyses of randomized controlled trials to evaluate the joint efficacy of FMT and laxatives in functional constipation.<br><br>METHODS: We performed a systematic literature search of 6 electronic databases as of August 11, 2020. Randomized controlled trial of FMT together with laxatives vs laxatives alone in functional constipation in adults were included. Two reviewers independently performed the screening, data extraction, and bias assessment. Dichotomous outcome data were synthesized by risk ratio, and measurement data by weighted mean difference (WMD).<br><br>RESULTS: A total of 1400 records were identified, of which 5 were eligible (409 patients). Overall, compared to laxatives alone, combined therapy of FMT and laxatives more significantly improved total effective rate (risk ratio: 1.35; 95% confidence interval [CI]: 1.14, 1.60; I2 = 13%), Bristol stool form scale score (WMD: 1.04; 95% CI: 0.57, 1.51; I2 = 76%), reduce Wexner score (WMD: -3.25; 95% CI: -5.58, -0.92; I2 = 92%), Knowles-Eccersley-Scott-Symptom (KESS) score (WMD: -5.65; 95% CI: -7.62, -3.69; I2 = 0%) and patient assessment of constipation quality of life score (WMD: -18.56; 95%; CI: -26.43, -10.68; I2 = 78%). No serious adverse events were reported. The majority of included studies had poor methodological quality.<br><br>CONCLUSION: Combined therapy of FMT and laxatives may be a reasonably effective and safe treatment for people with functional constipation. However, caution is needed with the interpretation of these data due to the small sample size, high heterogeneity, and low quality of the studies. Besides, we expect that more studies will be performed exploring the efficacy and safety of combined therapy for functional constipation.}, }
@article {pmid33827161, year = {2021}, author = {Dixon, CE and Bedenice, D and Restifo, M and Mazan, M and Brewer, P and Knafo, SE}, title = {NEONATAL INTENSIVE CARE OF 10 HOSPITALIZED GIRAFFE CALVES (GIRAFFA CAMELOPARDALIS) REQUIRING HAND-REARING.}, journal = {Journal of zoo and wildlife medicine : official publication of the American Association of Zoo Veterinarians}, volume = {52}, number = {1}, pages = {57-66}, doi = {10.1638/2019-0021}, pmid = {33827161}, issn = {1042-7260}, mesh = {Animal Husbandry/*methods ; Animals ; *Animals, Newborn ; Critical Care/*methods ; Female ; *Giraffes ; Hospitals, Animal ; Male ; Retrospective Studies ; }, abstract = {This retrospective case series describes the clinicopathologic findings, diagnoses, treatment, and outcomes of 10 hand-reared newborn giraffe (Giraffa camelopardalis) calves admitted to a university teaching hospital for intensive care. Ten calves (five males, five females; nine reticulated giraffes [Giraffa camelopardalis reticulata], one Masai giraffe [G. c. tippelskirchi]), were admitted under 2 days of age. Inadequate transfer of passive immunity was suspected in 5 of 10 calves based on assessment of serum total solids and globulin values. These calves were treated with oral frozen bovine colostrum and/or intravenous hyperimmune bovine plasma. Diarrhea occurred in 6 of 10 calves and was managed with supportive care, fecal microbiota transplantation, and limiting milk intake (offering 10% body weight [BW] in milk per day, while feeding <2 L per meal at 2- to 4-hr intervals). Less common diagnoses included pneumonia (n = 3) and mycoplasma-associated septic arthritis (n = 1). Eight calves received systemic antimicrobial therapy. Hyperlactatemia (lactate > 5 mmol/L; n = 8) and hypercreatininemia (creatinine > 2.0 mg/dl, n = 7) were the most common presenting laboratory abnormalities, which resolved with intravenous fluid therapy. All neonatal giraffes survived to discharge after a median hospitalization of 9.5 days (range, 5-37 days) and were successfully hand-reared at their place of birth. In conclusion, neonatal giraffe calves can be intensively managed in a hospital environment. Diarrhea was a common clinical problem and can be related to feeding regimens. Intravenous hyperimmune bovine plasma infusion was well tolerated to manage failure of transfer of passive immunity in calves with inadequate colostrum administration. The current study supports that compromised neonatal giraffe calves may carry an excellent prognosis after early, intensive intervention.}, }
@article {pmid33827154, year = {2021}, author = {Park, SY and Seo, GS}, title = {Fecal Microbiota Transplantation: Is It Safe?.}, journal = {Clinical endoscopy}, volume = {54}, number = {2}, pages = {157-160}, pmid = {33827154}, issn = {2234-2400}, abstract = {Fecal microbiota transplantation (FMT) is an accepted procedure for the management of recurrent Clostridioides difficile infections. FMT is generally considered safe and well-tolerated - even in high-risk patients. Most short-term risks are mild and known to be associated with delivery methods. Long-term side effects have not been established, and no signs of harm have been found to date. However, causality for several microbiome-associated diseases has to be established. Even though FMT is generally considered safe with strict donor screening, serious adverse events have been recently associated with the FMT product from the stool bank, where screening for multi-drug resistant organisms is not included in protocols. Here, we discuss the adverse events associated with FMT and safety issues.}, }
@article {pmid33824200, year = {2021}, author = {Xiao, L and Yan, J and Yang, T and Zhu, J and Li, T and Wei, H and Chen, J}, title = {Fecal Microbiome Transplantation from Children with Autism Spectrum Disorder Modulates Tryptophan and Serotonergic Synapse Metabolism and Induces Altered Behaviors in Germ-Free Mice.}, journal = {mSystems}, volume = {6}, number = {2}, pages = {}, pmid = {33824200}, issn = {2379-5077}, abstract = {To determine the relationship of the gut microbiota and its metabolites with autism spectrum disorder (ASD)-like behaviors and preliminarily explore the potential molecular mechanisms, the fecal microbiota from donors with ASD and typically developing (TD) donors were transferred into germ-free (GF) mice to obtain ASD-FMT mice and TD-FMT mice, respectively. Behavioral tests were conducted on these mice after 3 weeks. 16S rRNA gene sequencing of the cecal contents and untargeted metabolomic analysis of the cecum, serum, and prefrontal cortex were performed. Untargeted metabolomics was also used to analyze fecal samples of TD and ASD children. Western blotting detected the protein expression levels of tryptophan hydroxylase 1 (TPH1), serotonin transporter (SERT), and serotonin 1A receptor (5-HT1AR) in the colon and TPH2, SERT, and 5-HT1AR in the prefrontal cortex of mice. ASD-FMT mice showed ASD-like behavior and a microbial community structure different from that of TD-FMT mice. Tryptophan and serotonin metabolisms were altered in both ASD and TD children and ASD-FMT and TD-FMT mice. Some microbiota may be related to tryptophan and serotonin metabolism. Compared with TD-FMT mice, ASD-FMT mice showed low SERT and 5-HT1AR and high TPH1 expression levels in the colon. In the prefrontal cortex, the expression levels of TPH2 and SERT were increased in the ASD-FMT group relative to the TD-FMT group. Therefore, the fecal microbiome of ASD children can lead to ASD-like behaviors, different microbial community structures, and altered tryptophan and serotonin metabolism in GF mice. These changes may be related to changes in some key proteins involved in the synthesis and transport of serotonin.IMPORTANCE The relationship between the gut microbiota and ASD is not yet fully understood. Numerous studies have focused on the differences in intestinal microbial and metabolism profiles between TD and ASD children. However, it is still not clear if these microbes and metabolites cause the development of ASD symptoms. Here, we collected fecal samples from TD and ASD children, transplanted them into GF mice, and found that the fecal microbiome of ASD children can lead to ASD-like behaviors, different microbial community structures, and altered tryptophan and serotonin metabolism in GF mice. We also demonstrated that tryptophan and serotonin metabolism was also altered in ASD and TD children. Together, these findings confirm that the microbiome from children with ASD may lead to ASD-like behavior of GF mice through metabolites, especially tryptophan and serotonin metabolism.}, }
@article {pmid33820996, year = {2021}, author = {Wilkinson, JE and Franzosa, EA and Everett, C and Li, C and ,  and ,  and Hu, FB and Wirth, DF and Song, M and Chan, AT and Rimm, E and Garrett, WS and Huttenhower, C}, title = {A framework for microbiome science in public health.}, journal = {Nature medicine}, volume = {27}, number = {5}, pages = {766-774}, pmid = {33820996}, issn = {1546-170X}, support = {P30 DK046200/DK/NIDDK NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; C10674/A27140/CRUK_/Cancer Research UK/United Kingdom ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Biomedical Research/*methods ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*physiology ; Health Status ; Humans ; Prebiotics/administration &amp; dosage ; Probiotics/therapeutic use ; Public Health/education/*methods ; }, abstract = {Human microbiome science has advanced rapidly and reached a scale at which basic biology, clinical translation and population health are increasingly integrated. It is thus now possible for public health researchers, practitioners and policymakers to take specific action leveraging current and future microbiome-based opportunities and best practices. Here we provide an outline of considerations for research, education, interpretation and scientific communication concerning the human microbiome and public health. This includes guidelines for population-scale microbiome study design; necessary physical platforms and analysis methods; integration into public health areas such as epidemiology, nutrition, chronic disease, and global and environmental health; entrepreneurship and technology transfer; and educational curricula. Particularly in the near future, there are both opportunities for the incorporation of microbiome-based technologies into public health practice, and a growing need for policymaking and regulation around related areas such as prebiotic and probiotic supplements, novel live-cell therapies and fecal microbiota transplants.}, }
@article {pmid33812983, year = {2021}, author = {Wang, F and Song, M and Lu, X and Zhu, X and Deng, J}, title = {Gut microbes in gastrointestinal cancers.}, journal = {Seminars in cancer biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.semcancer.2021.03.037}, pmid = {33812983}, issn = {1096-3650}, abstract = {Gut microbes (GMs), dominated by bacteria, play important roles in many physiological processes. The structures and functions of GMs are closely related to human health, the occurrence and development of diseases and the rapid recovery of the body. Gastrointestinal cancers are the major diseases affecting human health worldwide. With the development of metagenomic technology and the wide application of new generation sequencing technology, a large number of studies suggest that complex GMs are related to the occurrence and development of gastrointestinal cancers. Fecal microbiota transplantation (FMT) and probiotics can treat and prevent the occurrence of gastrointestinal cancers. This article reviews the latest research progress of microbes in gastrointestinal cancers from the perspectives of the correlation, the influence mechanism and the application, so as to provide new directions for the prevention, early diagnosis and treatment of gastrointestinal cancers.}, }
@article {pmid33809421, year = {2021}, author = {Kazemian, N and Kao, D and Pakpour, S}, title = {Fecal Microbiota Transplantation during and Post-COVID-19 Pandemic.}, journal = {International journal of molecular sciences}, volume = {22}, number = {6}, pages = {}, pmid = {33809421}, issn = {1422-0067}, mesh = {COVID-19/*epidemiology ; Clostridium Infections/therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Gastrointestinal Microbiome ; Humans ; Lung/physiopathology ; *Pandemics ; Treatment Outcome ; }, abstract = {COVID-19 is a major pandemic facing the world today, which has implications on current microbiome-based treatments such as fecal microbiota transplantation (FMT) used for recurrent Clostridioides difficile infections. The bidirectional relationship between the inhabitants of our gut, the gut microbiota, and COVID-19 pathogenesis, as well as the underlying mechanism involved, must be elucidated in order to increase FMT safety and efficacy. In this perspective, we discuss the crucial cross-talk between the gut microbiota and the lungs, known as the gut-lung axis, during COVID-19 infection, as well as the putative effect of these microorganisms and their functional activity (i.e., short chain fatty acids and bile acids) on FMT treatment. In addition, we highlight the urgent need to investigate the possible impact of COVID-19 on FMT safety and efficacy, as well as instilling stringent screening protocols of donors and recipients during COVID-19 and post-COVID-19 pandemic to produce a cohesive and optimized FMT treatment plan across all centers and in all countries across the globe.}, }
@article {pmid33806843, year = {2021}, author = {Basson, AR and Cominelli, F and Rodriguez-Palacios, A}, title = {'Statistical Irreproducibility' Does Not Improve with Larger Sample Size: How to Quantify and Address Disease Data Multimodality in Human and Animal Research.}, journal = {Journal of personalized medicine}, volume = {11}, number = {3}, pages = {}, pmid = {33806843}, issn = {2075-4426}, support = {DK118373/NH/NIH HHS/United States ; P30DK097948/NH/NIH HHS/United States ; P01DK091222/NH/NIH HHS/United States ; T32DK083251/NH/NIH HHS/United States ; F32DK117585/NH/NIH HHS/United States ; }, abstract = {Poor study reproducibility is a concern in translational research. As a solution, it is recommended to increase sample size (N), i.e., add more subjects to experiments. The goal of this study was to examine/visualize data multimodality (data with >1 data peak/mode) as cause of study irreproducibility. To emulate the repetition of studies and random sampling of study subjects, we first used various simulation methods of random number generation based on preclinical published disease outcome data from human gut microbiota-transplantation rodent studies (e.g., intestinal inflammation and univariate/continuous). We first used unimodal distributions (one-mode, Gaussian, and binomial) to generate random numbers. We showed that increasing N does not reproducibly identify statistical differences when group comparisons are repeatedly simulated. We then used multimodal distributions (>1-modes and Markov chain Monte Carlo methods of random sampling) to simulate similar multimodal datasets A and B (t-test-p = 0.95; N = 100,000), and confirmed that increasing N does not improve the 'reproducibility of statistical results or direction of the effects'. Data visualization with violin plots of categorical random data simulations with five-integer categories/five-groups illustrated how multimodality leads to irreproducibility. Re-analysis of data from a human clinical trial that used maltodextrin as dietary placebo illustrated multimodal responses between human groups, and after placebo consumption. In conclusion, increasing N does not necessarily ensure reproducible statistical findings across repeated simulations due to randomness and multimodality. Herein, we clarify how to quantify, visualize and address disease data multimodality in research. Data visualization could facilitate study designs focused on disease subtypes/modes to help understand person-person differences and personalized medicine.}, }
@article {pmid33805552, year = {2021}, author = {Pham, VT and Calatayud, M and Rotsaert, C and Seifert, N and Richard, N and Van den Abbeele, P and Marzorati, M and Steinert, RE}, title = {Antioxidant Vitamins and Prebiotic FOS and XOS Differentially Shift Microbiota Composition and Function and Improve Intestinal Epithelial Barrier In Vitro.}, journal = {Nutrients}, volume = {13}, number = {4}, pages = {}, pmid = {33805552}, issn = {2072-6643}, mesh = {Adult ; Antioxidants/*pharmacology ; Bacteria/classification/drug effects ; Caco-2 Cells ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects ; Glucuronates/*pharmacology ; HT29 Cells ; Humans ; Intestinal Mucosa/drug effects/microbiology ; Male ; Oligosaccharides/*pharmacology ; Oxidation-Reduction ; *Prebiotics ; Vitamins/*pharmacology ; }, abstract = {Human gut microbiota (HGM) play a significant role in health and disease. Dietary components, including fiber, fat, proteins and micronutrients, can modulate HGM. Much research has been performed on conventional prebiotics such as fructooligosaccharides (FOS) and galactooligosaccharides (GOS), however, novel prebiotics or micronutrients still require further validation. We assessed the effect of FOS, xylooligosaccharides (XOS) and a mixture of an antioxidant vitamin blend (AOB) on gut microbiota composition and activity, and intestinal barrier in vitro. We used batch fermentations and tested the short-term effect of different products on microbial activity in six donors. Next, fecal inocula from two donors were used to inoculate the simulator of the human microbial ecosystem (SHIME) and after long-term exposure of FOS, XOS and AOB, microbial activity (short- and branched-chain fatty acids and lactate) and HGM composition were evaluated. Finally, in vitro assessment of intestinal barrier was performed in a Transwell setup of differentiated Caco-2 and HT29-MTX-E12 cells exposed to fermentation supernatants. Despite some donor-dependent differences, all three tested products showed beneficial modulatory effects on microbial activity represented by an increase in lactate and SCFA levels (acetate, butyrate and to a lesser extent also propionate), while decreasing proteolytic markers. Bifidogenic effect of XOS was consistent, while AOB supplementation appears to exert a specific impact on reducing F. nucleatum and increasing butyrate-producing B. wexlerae. Functional and compositional microbial changes were translated to an in vitro host response by increases of the intestinal barrier integrity by all the products and a decrease of the redox potential by AOB supplementation.}, }
@article {pmid33804928, year = {2021}, author = {Schmidt, EKA and Raposo, PJF and Madsen, KL and Fenrich, KK and Kabarchuk, G and Fouad, K}, title = {What Makes a Successful Donor? Fecal Transplant from Anxious-Like Rats Does Not Prevent Spinal Cord Injury-Induced Dysbiosis.}, journal = {Biology}, volume = {10}, number = {4}, pages = {}, pmid = {33804928}, issn = {2079-7737}, support = {542589//Craig H. Neilsen Foundation/ ; }, abstract = {Spinal cord injury (SCI) causes gut dysbiosis and an increased prevalence of depression and anxiety. Previous research showed a link between these two consequences of SCI by using a fecal transplant from healthy rats which prevented both SCI-induced microbiota changes and the subsequent development of anxiety-like behaviour. However, whether the physical and mental state of the donor are important factors in the efficacy of FMT therapy after SCI remains unknown. In the present study, rats received a fecal transplant following SCI from uninjured donors with increased baseline levels of anxiety-like behaviour and reduced proportion of Lactobacillus in their stool. This fecal transplant increased intestinal permeability, induced anxiety-like behaviour, and resulted in minor but long-term alterations in the inflammatory state of the recipients compared to vehicle controls. There was no significant effect of the fecal transplant on motor recovery in rehabilitative training, suggesting that anxiety-like behaviour did not affect the motivation to participate in rehabilitative therapy. The results of this study emphasize the importance of considering both the microbiota composition and the mental state of the donor for fecal transplants following spinal cord injury.}, }
@article {pmid33804464, year = {2021}, author = {Mocanu, V and Rajaruban, S and Dang, J and Kung, JY and Deehan, EC and Madsen, KL}, title = {Repeated Fecal Microbial Transplantations and Antibiotic Pre-Treatment Are Linked to Improved Clinical Response and Remission in Inflammatory Bowel Disease: A Systematic Review and Pooled Proportion Meta-Analysis.}, journal = {Journal of clinical medicine}, volume = {10}, number = {5}, pages = {}, pmid = {33804464}, issn = {2077-0383}, abstract = {The response of patients with inflammatory bowel disease (IBD) to fecal microbial transplantation (FMT) has been inconsistent possibly due to variable engraftment of donor microbiota. This failure to engraft has resulted in the use of several different strategies to attempt optimization of the recipient microbiota following FMT. The purpose of our study was to evaluate the effects of two distinct microbial strategies-antibiotic pre-treatment and repeated FMT dosing-on IBD outcomes. A systematic literature review was designed and implemented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A medical librarian conducted comprehensive searches in MEDLINE, Embase, Scopus, Web of Science Core Collection, and Cochrane Library on 25 November 2019 and updated on 29 January 2021. Primary outcomes of interest included comparing relapse and remission rates in patients with IBD for a single FMT dose, repeated FMT dosages, and antibiotic pre-treatment groups. Twenty-eight articles (six randomized trials, 20 cohort trials, two case series) containing 976 patients were identified. Meta-analysis revealed that both repeated FMT and antibiotic pre-treatment strategies demonstrated improvements in pooled response and remission rates. These clinical improvements were associated with increases in fecal microbiota richness and α-diversity, as well as the enrichment of several short-chain fatty acid (SCFA)-producing anaerobes including Bifidobacterium, Roseburia, Lachnospiraceae, Prevotella, Ruminococcus, and Clostridium related species.}, }
@article {pmid33804226, year = {2021}, author = {Lorente-Picón, M and Laguna, A}, title = {New Avenues for Parkinson's Disease Therapeutics: Disease-Modifying Strategies Based on the Gut Microbiota.}, journal = {Biomolecules}, volume = {11}, number = {3}, pages = {}, pmid = {33804226}, issn = {2218-273X}, support = {LCF/BQ/PR19/11700005//La Caixa Banking Foundation/ ; }, abstract = {Parkinson's disease (PD) is a multifactorial neurodegenerative disorder that currently affects 1% of the population over the age of 60 years, and for which no disease-modifying treatments exist. Neurodegeneration and neuropathology in different brain areas are manifested as both motor and non-motor symptoms in patients. Recent interest in the gut-brain axis has led to increasing research into the gut microbiota changes in PD patients and their impact on disease pathophysiology. As evidence is piling up on the effects of gut microbiota in disease development and progression, another front of action has opened up in relation to the potential usage of microbiota-based therapeutic strategies in treating gastrointestinal alterations and possibly also motor symptoms in PD. This review provides status on the different strategies that are in the front line (i.e., antibiotics; probiotics; prebiotics; synbiotics; dietary interventions; fecal microbiota transplantation, live biotherapeutic products), and discusses the opportunities and challenges the field of microbiome research in PD is facing.}, }
@article {pmid33800841, year = {2021}, author = {Ooijevaar, RE and van Nood, E and Goorhuis, A and Terveer, EM and van Prehn, J and Verspaget, HW and van Beurden, YH and Dijkgraaf, MGW and Keller, JJ}, title = {Ten-Year Follow-Up of Patients Treated with Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection from a Randomized Controlled Trial and Review of the Literature.}, journal = {Microorganisms}, volume = {9}, number = {3}, pages = {}, pmid = {33800841}, issn = {2076-2607}, abstract = {Fecal microbiota transplantation (FMT) has become a well-established treatment for recurrent Clostridioides difficile infection (rCDI). While short-term outcomes and adverse events relating to FMT have been well documented, there still is a paucity of data with regard to long-term safety. In this report, we describe the long-term follow-up of the prospective cohort of the first randomized controlled trial of FMT for rCDI, and review the existing literature. A total of 34 patients were treated with FMT for rCDI. Seven patients were still alive after a follow-up of more than 10 years and three patients were lost to follow-up. None of the 34 patients had experienced a new-onset autoimmune, gastrointestinal, or malignant disorder during follow-up. We did not find any deterioration or amelioration of pre-existing medical conditions. Furthermore, no deaths directly attributable to FMT could be identified. These findings are in accordance with the data in available literature. In conclusion, no long-term adverse events or complications directly attributable to FMT were found in our prospective cohort. Review of the available literature does not point to long-term risks associated with FMT in this elderly population, provided that carefully screened fecal suspensions are being used. No firm conclusion on the long-term safety of FMT in younger patients could be drawn.}, }
@article {pmid33795620, year = {2021}, author = {Leung, J and Pham, S}, title = {A Systematic Review of Fecal Microbiota Transplantation Versus Vancomycin for Treatment of Recurrent Clostridioides difficile Infection.}, journal = {Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates}, volume = {44}, number = {2}, pages = {106-115}, doi = {10.1097/SGA.0000000000000529}, pmid = {33795620}, issn = {1538-9766}, abstract = {Clostridioides difficile infection is a major clinical challenge, which may be associated with severe complications. Clostridioides difficile infection may result in repeated episodes of diarrhea, abdominal pain, and dehydration, leading to an increased risk of mortality. Increasingly high rates of recurrent Clostridioides difficile-associated diarrhea, refractory to antibiotic therapy, are difficult to treat. The suboptimal response to antibiotic therapy has led to the need for fecal microbiota transplantation in addition to the more commonly prescribed antibiotic, vancomycin. This systematic review aims to evaluate the effectiveness of fecal microbiota transplantation in the resolution of recurrent Clostridioides difficile infection in adults, compared with an oral vancomycin regimen alone. A systematic literature search was performed, resulting in three randomized control studies. Results from the studies are conflicting, with different variations of study outcomes. In two of the three randomized control trials, fecal microbiota transplantation was statistically significant in effectively resolving Clostridioides difficile infection, but not significant in the third. Although fecal microbiota transplantation results are promising, there are many different variables within the studies, and further research is recommended to explore the effects of these variables within larger sample sizes.}, }
@article {pmid33795522, year = {2021}, author = {Wang, H and Ren, S and Lv, H and Cao, L}, title = {Gut microbiota from mice with cerebral ischemia-reperfusion injury affects the brain in healthy mice.}, journal = {Aging}, volume = {13}, number = {7}, pages = {10058-10074}, pmid = {33795522}, issn = {1945-4589}, mesh = {Animals ; Anxiety/metabolism ; Behavior, Animal/physiology ; Brain/*metabolism ; Brain Ischemia/*metabolism ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Male ; Memory/physiology ; Metagenome ; Mice ; Neuronal Plasticity/physiology ; Reperfusion Injury ; }, abstract = {Gut microorganisms can profoundly influence brain function in the host and their behavior. Since altered brain functional connectivity (FC) has been implicated in various cerebrovascular disorders, including cerebral ischemia-reperfusion (I/R) injury, we hypothesized that gut microbiota in mice with cerebral I/R injury would affect brain FC when transplanted into germ-free mice. Metagenomic analysis of germ-free male C57BL/6J mice colonized with microbiota from mice with and without cerebral I/R injury showed a clear distinction in microbiota composition between mice colonized with control and I/R microbiota. The I/R microbiota-colonized mice showed decreased FC in the cingulate cortex, hippocampus, and thalamus, and exhibited increased anxiety as well as diminished spatial learning and memory and short-term object recognition memory. I/R microbiota-colonized mice also had significantly reduced dendritic spine density and synaptic protein levels and exhibited increased hippocampal inflammation. These results indicate that gut microbiota components from mice with cerebral I/R injury can alter animal behavior, brain functional connectivity, hippocampal neuronal plasticity, and neuroinflammation. Moreover, they increase our understanding of the mechanisms through which the gut microbiome contributes to the pathobiology of cerebrovascular diseases.}, }
@article {pmid33794724, year = {2021}, author = {Manrique, P and Zhu, Y and van der Oost, J and Herrema, H and Nieuwdorp, M and de Vos, WM and Young, M}, title = {Gut bacteriophage dynamics during fecal microbial transplantation in subjects with metabolic syndrome.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1-15}, pmid = {33794724}, issn = {1949-0984}, support = {R01 GM117361/GM/NIGMS NIH HHS/United States ; }, abstract = {Metabolic Syndrome (MetS) is a growing public health concern worldwide. Individuals with MetS have an increased risk for cardiovascular (CV) disease and type 2 diabetes (T2D). These diseases - in part preventable with the treatment of MetS - increase the chances of premature death and pose a great economic burden to health systems. A healthy gut microbiota is associated with a reduction in MetS, T2D, and CV disease. Treatment of MetS with fecal microbiota transplantation (FMT) can be effective, however, its success rate is intermediate and difficult to predict. Because bacteriophages significantly affect the microbiota membership and function, the aim of this pilot study was to explore the dynamics of the gut bacteriophage community after FMT in MetS subjects. We performed a longitudinal study of stool bacteriophages from healthy donors and MetS subjects before and after FMT treatment. Subjects were assigned to either a control group (self-stool transplant, n = 3) or a treatment group (healthy-donor-stool transplant; n-recipients = 6, n-donors = 5). Stool samples were collected over an 18-week period and bacteriophage-like particles were purified and sequenced. We found that FMT from healthy donors significantly alters the gut bacteriophage community. Subjects with better clinical outcome clustered closer to the heathy donor group, suggesting that throughout the treatment, their bacteriophage community was more similar to healthy donors. Finally, we identified bacteriophage groups that could explain these differences and we examined their prevalence in individuals from a larger cohort of MetS FMT trial.Trial information- http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2705; NTR 2705.}, }
@article {pmid33793160, year = {2021}, author = {Qian, Q and He, W and Tang, R and Ma, X}, title = {Implications of gut microbiota in autoimmune liver diseases.}, journal = {Minerva gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.23736/S2724-5985.21.02860-9}, pmid = {33793160}, issn = {2724-5365}, abstract = {Autoimmune liver diseases (AILD) is a group of immune-mediated liver inflammatory diseases with three major forms including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Interaction of both genetic and environmental factors leads to the breakdown of self-tolerance, hence resulting in hyper-responsive of autoantibodies and aggressive autoreactive immune cells. Genetic studies have identified dozens of risk loci associated with initiation and development of AILD. However, the role of exogenous factors remains unclear. Recently, both infectious and inflammatory diseases have been associated with microbiota, which colonizes multiple mucosal surfaces and participates in human physiological process and function in immune system, particularly influencing liver and biliary system via gut-liver axis. Emerging evidence on the role of gut microbiota has expanded our knowledge of AILD in both pathogenesis and potential therapeutic targets, along with putative diagnosis biomarkers. Herein we review the relationship between host and gut microbiota, discuss their potential roles in disease onset and progression, and summarize the compositional and functional alterations of the microbiota in AILD. We also highlight the microbiotabased therapeutics such as antibiotics and fecal microbiota transplantation (FMT).}, }
@article {pmid33785319, year = {2021}, author = {Bui, TPN and de Vos, WM}, title = {Next-generation therapeutic bacteria for treatment of obesity, diabetes, and other endocrine diseases.}, journal = {Best practice &amp; research. Clinical endocrinology &amp; metabolism}, volume = {35}, number = {3}, pages = {101504}, doi = {10.1016/j.beem.2021.101504}, pmid = {33785319}, issn = {1878-1594}, abstract = {The human gut microbiota has appeared as an important factor affecting host health and intestinal bacteria have recently emerged as potential therapeutics to treat diabetes and other endocrine diseases. These mainly anaerobic bacteria have been identified either via comparative "omics" analysis of the intestinal microbiota in healthy and diseased subjects or of data collected by fecal microbiota transplantation studies. Both approaches require advanced and in-depth sequencing technologies to perform massive genomic screening to select bacteria with potential benefits. It has been shown that these potentially therapeutic bacteria can either produce bioactive products that directly influence the host patho-physiology and endocrine systems or produce specific signaling molecules that may do so. These bioactive compounds can be formed via degradation of dietary or host-derived components or the conversion of intermediate compounds produced by fermentation of intestinal bacteria. Several of these bacteria have shown causality in preclinical models and entered clinical phase studies, while their mode of action is being analyzed. In this review, we summarize the research on the most promising bacterial candidates with therapeutic properties with a specific focus on diabetes.}, }
@article {pmid33777828, year = {2021}, author = {Li, C and Pi, G and Li, F}, title = {The Role of Intestinal Flora in the Regulation of Bone Homeostasis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {579323}, pmid = {33777828}, issn = {2235-2988}, mesh = {*Gastrointestinal Microbiome ; Homeostasis ; Humans ; Intestines ; Prebiotics ; *Probiotics ; }, abstract = {Intestinal flora located within the intestinal tract comprises a large number of cells, which are referred to as the second gene pool of the human body and form a complex symbiotic relationship with the host. The knowledge of the complex interaction between the intestinal flora and various life activities of the host is a novel and rapidly expanding field. Recently, many studies are being conducted on the relationship between the intestinal flora and bone homeostasis and indicate that the intestinal flora can regulate bone homeostasis via the host immune, metabolic, and endocrine systems. What's more, based on several clinical and preclinical pieces of evidence, changing the composition and function of the host intestinal flora through the application of probiotics, prebiotics, and fecal microbiota transplantation is being considered to be a potential novel target for the regulation of bone homeostasis. Here, we searched relevant literature and reviewed the role of the intestinal flora in the regulation of bone homeostasis and its modulating interventions.}, }
@article {pmid33776811, year = {2021}, author = {Qi, Z and Lyu, M and Yang, L and Yuan, H and Cao, Y and Zhai, L and Dang, W and Liu, J and Yang, F and Li, Y}, title = {A Novel and Reliable Rat Model of Autism.}, journal = {Frontiers in psychiatry}, volume = {12}, number = {}, pages = {549810}, pmid = {33776811}, issn = {1664-0640}, abstract = {Background: Autism spectrum disorders (ASD) is a complex neurodevelopmental disorder that lacks an ideal animal model to recapitulate the disease state of ASD. Previous studies have reported that transplanting gut microbiota of ASD patients into pregnant mice is sufficient to promote the changes of autism-like behavior in offspring. This study aims to explore whether fecal microbiota transplantation (FMT) can be used as a new method to establish the ASD animal model. Methods: We transplanted the fecal sample extract of ASD children into pregnant rats (rFMT) repeatedly to establish an ASD rat model (oFMT) and compare it with the classical valproic acid (VPA) model (oVPA). Results: First, we reveal that oFMT shows hypoevolutism and typical behavioral characteristics of ASD, consistent with the previous study. Second, the gut microbiota of oFMT mainly consists of Firmicutes and Bacteroidetes, recapitulating the abnormal gut microbiota of ASD. In oFMT, the abundance of Lactobacillus and Collinsella increased (Lactobacillus: oFMT 60.16%, oVPA 64.13%, oCON 40.11%; Collinsella: oFMT 3.73%, oVPA 1.39%, oCON 1.28%), compared with oVPA, gut microbiota also showed high consistency. Third, the expression of 5-hydroxytryptamine (5-HT) in oFMT serum increased, γ-aminobutyric acid (GABA) and norepinephrine (NE) in oFMT serum decreased. Fourth, the gut microbiota of oFMT also has some ASD characteristic gut microbiota not found in oVPA. Fifth, pregnant rat with VPA showed significant immune activation, while those with FMT showed relatively minor immune activation. Limitations: Although the mechanism of establishing FMT autism rat model (oFMT) has not clearly defined, the data show that the model has high structural validity, and FMT model is likely to be a new and reliable potential animal model of ASD, and will have potential value in studying gut microbiota of ASD. Conclusions: The FMT autism rat model has high structural validity, and the FMT model is likely to be a new and reliable potential animal model of ASD.}, }
@article {pmid33775619, year = {2021}, author = {Farhadfar, N and Gharaibeh, RZ and Dahl, WJ and Mead, L and Alabasi, KM and Newsome, R and IrizarryGatell, V and Weaver, MT and Al-Mansour, Z and Jobin, C and Lyon, D and Wingard, JR and Kelly, DL}, title = {Gut Microbiota Dysbiosis Associated with Persistent Fatigue in Hematopoietic Cell Transplantation Survivors.}, journal = {Transplantation and cellular therapy}, volume = {27}, number = {6}, pages = {498.e1-498.e8}, doi = {10.1016/j.jtct.2021.02.017}, pmid = {33775619}, issn = {2666-6367}, mesh = {Adenosine Deaminase ; Adult ; Cross-Sectional Studies ; Dysbiosis ; Fatigue ; *Gastrointestinal Microbiome ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Intercellular Signaling Peptides and Proteins ; Quality of Life ; RNA, Ribosomal, 16S ; Survivors ; }, abstract = {Fatigue is one of the most prevalent and distressing complications among hematopoietic stem cell transplantation (HCT) survivors, negatively affecting physical, social, and emotional domains of quality of life. Chronic systemic inflammation has been linked to alterations in nervous system activity and initiation of distressing symptoms, such as fatigue. Damage to gut mucosa due to alteration in gut microbiota (GM) composition and microbial translocation has been shown to increase systemic proinflammatory cytokines. The aim of this study was to evaluate the relationship between fatigue and GM by measuring the differences in GM composition in HCT survivors with and without persistent fatigue. This cross-sectional study included 30 adults who underwent HCT for a hematologic disease and were at least 1 year post-HCT. Patients with chronic graft-versus-host disease were excluded. Fatigue severity was assessed by the Brief Fatigue Inventory (BFI). Based on the BFI score, patients were grouped into 2 categories: 0 to 3 (without fatigue) and ≥4 (with fatigue). The V1 to V3 region of the 16S rRNA gene from fecal specimens was sequenced using the Illumina MiSeq. Sequencing reads were processed, denoised, and replicated, chimeras were filtered, amplicon sequence variants (ASVs) were generated, and taxonomy was assigned using DADA2. Beta diversity analysis through principal coordinate analysis was generated using the Bray-Curtis dissimilarity matrix, and the difference was tested using linear model with generalized least squares in R. An alpha diversity analysis was performed using Chao1. Linear discriminant analysis effect size (LEfSe) was used to find markers that differ between the 2 groups. Based on the BFI results, patients were categorized into 2 cohorts: with fatigue (n = 14) and without fatigue (n = 16). The 2 cohorts were similar in terms of demographics, disease, and transplant characteristics. Based on the GM analysis, there was a significant difference in GM composition (beta diversity) between the 2 cohorts (P = .001). Alpha diversity (richness) was also significantly lower in survivors with fatigue (P =.002). LEfSe analysis identified 46 discriminative features (P < .05; linear discriminant analysis score >2) whose relative abundance varied significantly among individuals with fatigue and those without fatigue. Ten ASVs were associated with the patients with fatigue, and 36 ASVs were associated with those without fatigue. Several ASVs enriched in survivors with fatigue included organisms such as Klebsiella and Enterococcus, which have been implicated in inflammatory bowel diseases. The ASVs enriched in the cohort without fatigue were members of the Ruminococcaceae family (Oscillospira spp) and the Lachnospiraceae family (Fusicatenibacter and Coprococcus spp), which are known to have the ability to ferment complex plant carbohydrates. These findings show an association between GM composition and fatigue and suggest a microbial contribution to clinically significant fatigue post-HCT, which may guide the development of new approaches to treating fatigue based on manipulation of the GM.}, }
@article {pmid33775068, year = {2021}, author = {Karolewska-Bochenek, K and Lazowska-Przeorek, I and Grzesiowski, P and Dziekiewicz, M and Dembinski, L and Albrecht, P and Radzikowski, A and Banaszkiewicz, A}, title = {Faecal Microbiota Transfer - a new concept for treating cytomegalovirus colitis in children with ulcerative colitis.}, journal = {Annals of agricultural and environmental medicine : AAEM}, volume = {28}, number = {1}, pages = {56-60}, doi = {10.26444/aaem/118189}, pmid = {33775068}, issn = {1898-2263}, mesh = {Adolescent ; Child ; Child, Preschool ; Colitis, Ulcerative/microbiology/*therapy/virology ; Colon/microbiology/virology ; Cytomegalovirus/*physiology ; Cytomegalovirus Infections/microbiology/*therapy/virology ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; Humans ; Male ; Pilot Projects ; Prospective Studies ; }, abstract = {INTRODUCTION: Cytomegalovirus (CMV) infection in patients with inflammatory bowel disease (IBD) is reactivated by the use of immunosuppressive drugs. CMV infection may produce IBD flares refractory to standard therapy.<br><br>OBJECTIVE: The aim of our study was to assess the efficacy and safety of faecal microbiota transplantation (FMT) for the treatment of CMV colitis in patients with ulcerative colitis (UC) flare.<br><br>MATERIAL AND METHODS: A total of 8 children, with mild to severe UC, positive for CMV PCR in colonic biopsies, received 50-100 ml FMT by nasogastric tube on 5 consecutive days in each of 2 weeks. During the study, the subjects were treated with 5ASA and FMT. Immunosuppressant therapy was withdrawn, when CMV colitis was diagnosed by positive DNA PCR in colonic tissues. The clinical response was defined as a decrease of Paediatric UC Activity Index by ≥20 points.<br><br>RESULTS: At the 6th week of the study, negative colonic CMV DNA PCR was measured after 10 infusions in 7/8 patients. For one boy, 20 infusions were administered to assess CMV elimination from colonic biopsies. A clinical response was observed in 3/8 patients, with clinical remission in 3/8 patients. Faecal calprotectin decreased significantly in 3 patients. CRP normalized in 2 patients after 6 weeks. No serious adverse effects were observed during and after infusions.<br><br>CONCLUSIONS: FMT seems to be an effective and safe treatment option for CMV colitis in children with UC. This is the first study to demonstrate the application of FMT as a new therapeutic option for CMV colitis.}, }
@article {pmid33773125, year = {2021}, author = {Zaman, A and Qazi, T and Pai, P and Peters, P and Nicolaysen, S and Olesen, SW}, title = {Carriage rates of multidrug-resistant organisms among prospective stool donors.}, journal = {The Lancet. Infectious diseases}, volume = {21}, number = {4}, pages = {454-455}, doi = {10.1016/S1473-3099(21)00091-8}, pmid = {33773125}, issn = {1474-4457}, mesh = {Carrier State/epidemiology ; *Drug Resistance, Multiple, Bacterial ; *Fecal Microbiota Transplantation ; Feces ; Humans ; Prospective Studies ; Quarantine ; Retrospective Studies ; }, }
@article {pmid33766699, year = {2021}, author = {Munshi, S}, title = {A depressed gut makes for a depressed brain via vagal transmission.}, journal = {Brain, behavior, and immunity}, volume = {95}, number = {}, pages = {15-16}, doi = {10.1016/j.bbi.2021.03.017}, pmid = {33766699}, issn = {1090-2139}, mesh = {Animals ; Brain ; *Depression ; *Fecal Microbiota Transplantation ; Mice ; Mice, Knockout ; Phenotype ; Vagus Nerve ; alpha7 Nicotinic Acetylcholine Receptor ; }, }
@article {pmid33765728, year = {2021}, author = {Moon, CM and Hong, SN}, title = {Fecal Microbiota Transplantation beyond Clostridioides Difficile Infection.}, journal = {Clinical endoscopy}, volume = {54}, number = {2}, pages = {149-151}, pmid = {33765728}, issn = {2234-2400}, abstract = {With advancing analytical methods for gut microbes, many studies have been conducted, revealing that gut microbes cause various diseases, including gastrointestinal and non-gastrointestinal diseases. Accordingly, studies have been actively conducted to analyze the effects on the prevention and treatment of these diseases through changes in intestinal microbes and control of dysbiosis. Fecal microbiota transplantation (FMT) is an effort and is currently being applied to Clostridioides difficile treatment in Korea. Many studies have demonstrated the application of FMT in inflammatory bowel disease, irritable bowel syndrome, non-alcoholic fatty liver disease, metabolic syndrome, obesity, and diabetes. With further studies and accumulation of evidence, FMT could help treat presently untreatable diseases in clinical practice.}, }
@article {pmid33763383, year = {2021}, author = {Chen, ZJ and Liang, CY and Yang, LQ and Ren, SM and Xia, YM and Cui, L and Li, XF and Gao, BL}, title = {Association of Parkinson's Disease With Microbes and Microbiological Therapy.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {619354}, pmid = {33763383}, issn = {2235-2988}, mesh = {Catechol O-Methyltransferase ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Levodopa ; *Parkinson Disease/drug therapy ; }, abstract = {Parkinson's disease (PD) is the most common movement disorder in the world, affecting 1-2 per 1,000 of the population. The main pathological changes of PD are damage of dopaminergic neurons in substantia nigra of the central nervous system and formation of Lewy bodies. These pathological changes also occur in the intestinal tract and are strongly associated with changes in intestinal flora. By reviewing the research progress in PD and its association with intestinal flora in recent years, this review expounded the mechanism of action between intestinal flora and PD as well as the transmission mode of α - synuclein in neurons. In clinical studies, β diversity of intestinal flora in PD patients was found to change significantly, with Lactobacillusaceae and Verrucomicrobiaceae being significantly increased and Lachnospiraceae and Prevotellaceae being significantly decreased. In addition, a longer PD course was associated with fewer bacteria and probiotics producing short chain fatty acids, but more pathogenic bacteria. Moreover, the motor symptoms of PD patients may be related to Enterobacteriaceae and bacteria. Most importantly, catechol-O-methyltransferase inhibitors and anticholinergic drugs could change the intestinal flora of PD patients and increase the harmful flora, whereas other anti-PD drugs such as levodopa, dopamine agonist, monoamine oxidase inhibitors, and amantadine did not have these effects. Probiotics, prebiotics, and synbiotics treatment had some potential values in improving the constipation of PD patients, promoting the growth of probiotics, and improving the level of intestinal inflammation. At present, there were only a few case studies and small sample studies which have found certain clinical efficacy of fecal microbiome transplants. Further studies are necessary to elaborate the relationship of PD with microbes.}, }
@article {pmid33761228, year = {2021}, author = {Gweon, TG and Na, SY}, title = {Next Generation Fecal Microbiota Transplantation.}, journal = {Clinical endoscopy}, volume = {54}, number = {2}, pages = {152-156}, pmid = {33761228}, issn = {2234-2400}, abstract = {Fecal microbiota transplantation (FMT) is considered as an effective treatment for Clostridioides difficile infection. However, the precise mechanism of FMT is yet to be determined. Human stool consists of the gut microbiota, bacterial debris, and metabolic products. Of these, the intestinal microbiota is the most important factor that exerts therapeutic efficacy in FMT. Fresh donor stool, blended with normal saline, has been employed for traditional FMT. Nevertheless, stool processing is a major impediment in FMT. Frozen stool and capsule formulations have similar efficacy to that of fresh stool. In addition, several novel stool products have been identified. A stool bank that provides stool products with pre-screened donor stool has been established to help physicians and thereby facilitate FMT. Recent next-generation sequencing techniques have been key in facilitating the detailed analysis of the microbiota and gut environment of individual donors and recipients.}, }
@article {pmid33759066, year = {2021}, author = {Cheng, F and Huang, Z and Wei, W and Li, Z}, title = {Fecal microbiota transplantation for Crohn's disease: a systematic review and meta-analysis.}, journal = {Techniques in coloproctology}, volume = {25}, number = {5}, pages = {495-504}, pmid = {33759066}, issn = {1128-045X}, mesh = {*Crohn Disease/therapy ; Fecal Microbiota Transplantation ; Feces ; Humans ; *Inflammatory Bowel Diseases ; Intestines ; Treatment Outcome ; }, abstract = {BACKGROUND: Crohn's disease (CD) is a chronic idiopathic inflammatory intestinal disorder associated with fecal dysbiosis. Fecal microbiota transplantation (FMT) is an emerging treatment approach for CD. But its efficacy and safety remain controversial. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of FMT in CD patients.<br><br>METHODS: Electronic databases were searched for studies that reported efficacy and/or safety of FMT for CD. Clinical remission was established as the primary outcome. Secondary outcome was clinical response. Odds ratios with 95% confidence intervals (CIs) were reported.<br><br>RESULTS: In all, 12 trials were included in our study. Pooled analysis showed that 0.62 (95% CI 0.48, 0.81) of CD patients achieved clinical remission and 0.79 (95% CI 0.71, 0.89) of CD patients achieved clinical response post-FMT. Sub-analyses suggested the rate of clinical remission with fresh stool FMT was higher than with frozen stool FMT (73% vs 43%; p < 0.05). Most adverse events were minor and self-resolving and no major FMT-related adverse event has been reported so far.<br><br>CONCLUSIONS: The evidence showed that FMT is an effective and safe therapy for CD. FMT may be successful because it increases the overall diversity of enteric microbiome. Additional randomized controlled studies are needed.}, }
@article {pmid33758177, year = {2021}, author = {Wang, W and Zhai, D and Bai, Y and Xue, K and Deng, L and Ma, L and Du, T and Ye, Z and Qu, D and Xiang, A and Chen, G and Zhao, Y and Wang, L and Lu, Z}, title = {Loss of QKI in macrophage aggravates inflammatory bowel disease through amplified ROS signaling and microbiota disproportion.}, journal = {Cell death discovery}, volume = {7}, number = {1}, pages = {58}, pmid = {33758177}, issn = {2058-7716}, abstract = {Inflammatory bowel disease (IBD) is a refractory chronic inflammatory illness of the gastrointestinal (GI) tract. Macrophage exerts an important role in IBD development. QKI, as an RNA binding protein, was related with inflammatory responses in bacterial infections by regulating the polarization of macrophages. Therefore, we suspected that QKI-regulated macrophages have the potential to play a certain role in IBD and the underlying mechanism. Our results demonstrated that the mice with macrophage-specific deletion of QKI induced with dextran sodium sulfate (DSS) are more susceptible to IBD development, exhibited a severe leaky gut barrier phenotype and higher intense oxidative stress, which are rescued by treating with butylated hydroxyanisole (BHA), an agonist of NRF2. Mechanically, we observed that Keap1 mRNA in the nucleus was exported to the cytoplasm after LPS stimuli in parallel with QKI reductions, and the removal of QKI by shRNA facilitated Keap1 mRNA nuclear exporting and expression in cytoplasm, consequently NRF2 activation in nucleus was weakened, and led to the impaired antioxidant abilities. In addition, mice models of fecal microbiota transplant (FMT) and the co-culturing of mice epithelia cells with feces derived from the DSS-treated QKI-deficit mice revealed consistently aggravated colitis along with a severe oxidative stress; 16S sequencing analysis substantiated the altered compositions of commensal bacteria too. Overall, the current study represents the first effort to explore the anti-oxidant role of QKI in the intestinal macrophage via post-transcriptional regulation of Keap1 mRNA localization and the relevant NRF2 antioxidant signaling, and the disproportional changes in the microbiota were attributable to the mediation of pathogenic damage in the IBD development of QKI-deficit mice.}, }
@article {pmid33757553, year = {2021}, author = {Santiago, M and Olesen, SW}, title = {16S rRNA sequencing of samples from universal stool bank donors.}, journal = {BMC research notes}, volume = {14}, number = {1}, pages = {108}, pmid = {33757553}, issn = {1756-0500}, mesh = {*Clostridium Infections ; *Fecal Microbiota Transplantation ; Feces ; Humans ; RNA, Ribosomal, 16S/genetics ; Tissue Donors ; }, abstract = {OBJECTIVES: Universal stool banks provide stool to physicians for use in treating recurrent Clostridioides difficile infection via fecal microbiota transplantation. Stool donors providing the material are rigorously screened for diseases and disorders with a potential microbiome etiology, and they are likely healthier than the controls in most microbiome datasets. 16S rRNA sequencing was performed on samples from a selection of stool donors at a large stool bank, OpenBiome, to characterize their gut microbial community and to compare samples across different timepoints and sequencing runs.<br><br>DATA DESCRIPTION: 16S rRNA sequencing was performed on 200 samples derived from 170 unique stool donations from 86 unique donors. Samples were sequenced on 11 different sequencing runs. We are making this data available because rigorously screened, likely very healthy stool donors may be useful for characterizing and understanding microbial community differences across different populations and will help shed light into the how the microbiome community promotes health and disease.}, }
@article {pmid33757127, year = {2021}, author = {Zhang, Y and Zhang, S and Li, B and Luo, Y and Gong, Y and Jin, X and Zhang, J and Zhou, Y and Zhuo, X and Wang, Z and Zhao, X and Han, X and Gao, Y and Yu, H and Liang, D and Zhao, S and Sun, D and Wang, D and Xu, W and Qu, G and Bo, W and Li, D and Wu, Y and Li, Y}, title = {Gut microbiota dysbiosis promotes age-related atrial fibrillation by lipopolysaccharide and glucose-induced activation of NLRP3-inflammasome.}, journal = {Cardiovascular research}, volume = {}, number = {}, pages = {}, doi = {10.1093/cvr/cvab114}, pmid = {33757127}, issn = {1755-3245}, abstract = {AIMS: Aging is the most significant contributor to the increasing prevalence of atrial fibrillation (AF). The gut microbiota dysbiosis is involved in age-related diseases. However, whether the aged-associated dysbiosis contributes to age-related AF is still unknown. Direct demonstration that the aged gut microbiota is sufficient to transmit the enhanced AF susceptibility in a young host via microbiota-intestinal barrier-atria axis has not yet been reported. This study aimed to determine whether gut microbiota dysbiosis affects age-related AF.<br><br>METHODS AND RESULTS: Herein, by using a fecal microbiota transplantation (FMT) rat model, we demonstrated that the high AF susceptibility of aged rats could be transmitted to a young host. Specially, we found the dramatically increased levels of circulating lipopolysaccharide (LPS) and glucose led to the up-regulated expression of NLR family pyrin domain containing 3 (NLRP3)-inflammasome, promoting the development of AF which depended on the enhanced atrial fibrosis in recipient host. Inhibition of inflammasome by a potent and selective inhibitor of the NLRP3 inflammasome, MCC950, resulted in a lower atrial fibrosis and AF susceptibility. Then we conducted cross-sectional clinical studies to explore the effect of aging on the altering trends with glucose levels and circulating LPS among clinical individuals in two China hospitals. We found that both of serum LPS and glucose levels were progressively increased in elderly patients as compared with those young. Furthermore, the aging phenotype of circulating LPS and glucose levels, intestinal structure and atrial NLRP3-inflammasome of rats were also confirmed in clinical AF patients. Finally, aged rats colonized with youthful microbiota restored intestinal structure and atrial NLRP3-inflammasome activity, which suppressed the development of aged-related AF.<br><br>CONCLUSIONS: Collectively, these studies described a novel causal role of aberrant gut microbiota in the pathogenesis of age-related AF, which indicates that the microbiota-intestinal barrier-atrial NLRP3 inflammasome axis may be a rational molecular target for the treatment of aged-related arrhythmia disease.<br><br>TRANSLATIONAL PERSPECTIVE: The current study demonstrates that aged-associated microbiota dysbiosis promotes AF in part through a microbiota-gut-atria axis. Increased AF susceptibility due to enhanced atrial NLRP3-inflammasome activity by LPS and high glucose was found in an aged FMT rat model, and also confirmed within elderly clinical individuals. In a long-term FMT rat study, the AF susceptibility was ameliorated by treatment with youthful microbiota. The present findings can further increase our understanding of aged-related AF and address a promising therapeutic strategy that involves modulation of gut microbiota composition.}, }
@article {pmid33754054, year = {2021}, author = {Zhang, SL and Mao, YQ and Zhang, ZY and Li, ZM and Kong, CY and Chen, HL and Cai, PR and Han, B and Ye, T and Wang, LS}, title = {Pectin supplement significantly enhanced the anti-PD-1 efficacy in tumor-bearing mice humanized with gut microbiota from patients with colorectal cancer.}, journal = {Theranostics}, volume = {11}, number = {9}, pages = {4155-4170}, pmid = {33754054}, issn = {1838-7640}, mesh = {Aged ; Animals ; Antibodies, Monoclonal/*therapeutic use ; Bacteria ; CD8-Positive T-Lymphocytes/drug effects/metabolism ; Cell Line, Tumor ; Colorectal Neoplasms/*drug therapy/*metabolism ; Fatty Acids, Volatile/metabolism ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Pectins/*administration &amp; dosage ; Programmed Cell Death 1 Receptor/*antagonists &amp; inhibitors ; RNA, Ribosomal, 16S/metabolism ; Tumor Microenvironment/drug effects ; }, abstract = {Background: Anti-PD-1-based immunotherapy has emerged as a promising therapy for several cancers. However, it only benefits a small subset of colorectal cancer (CRC) patients. Mounting data supports the pivotal role of gut microbiota in shaping immune system. Pectin, a widely consumed soluble fiber, has been reported to ameliorate the imbalance of gut microbiota. Therefore, we aimed to explore the effect and the underlying mechanisms of pectin in improving anti-PD-1 mAb efficacy. Methods: The C57BL/6 mice were treated with a broad-spectrum antibiotic (ATB) cocktail to depleted endogenous gut microbiota and subsequently humanized with feces from healthy controls or newly diagnosed CRC patients. The antitumor efficacies of anti-PD-1 mAb combined with or without pectin were assessed using these mice. Flow cytometry and immunohistochemistry (IHC) were conducted to investigate the tumor immune microenvironment after treatment. The gut microbiota profiles and short-chain fatty acids (SCFAs) levels were determined by 16S ribosomal RNA (16S rRNA) gene sequencing and gas chromatography-mass spectrometry (GC-MS), respectively. The effect of gut microbiota on anti-PD-1 mAb efficacy after pectin supplement was further tested by fecal microbiota transplantation (FMT). Results: The anti-PD-1 mAb efficacy was largely impaired in the mice humanized with feces from newly diagnosed CRC patients compared to those from healthy controls. However, pectin significantly enhanced the anti-PD-1 mAb efficacy in the tumor-bearing mice humanized with CRC patient gut microbiota. Flow cytometry and IHC analysis revealed increased T cell infiltration and activation in the tumor microenvironment of mice treated with anti-PD-1 mAb plus pectin. In vivo depletion of CD8+ T cells diminished the anti-tumor effect of anti-PD-1 mAb combined with pectin. 16S rRNA gene sequencing showed that pectin significantly increased gut microbial diversity and beneficially regulated microbial composition. In addition, we identified unique bacterial modules that were significantly enriched in the anti-PD-1 mAb + pectin group, which composed of butyrate-producing bacteria indicative of good response to immunotherapy. Meanwhile, GC-MS showed that pectin altered the level of SCFA butyrate. Furthermore, butyrate, a main product of dietary fiber in gut microbial fermentation, was found to be sufficient to promote T cells infiltration and thus enhance the efficacy of anti-PD-1 mAb. In addition, FMT demonstrated the effects of pectin were dependent on gut microbiota. Importantly, the beneficial effects of pectin were confirmed in the mice humanized with gut microbiota from patient with resistance to anti-PD-1 mAb. Conclusion: Pectin facilitated the anti-PD-1 mAb efficacy in CRC via regulating the T cell infiltration in the tumor microenvironment, which was potentially mediated by the metabolite butyrate.}, }
@article {pmid33754024, year = {2021}, author = {Lu, J and Chen, PP and Zhang, JX and Li, XQ and Wang, GH and Yuan, BY and Huang, SJ and Liu, XQ and Jiang, TT and Wang, MY and Liu, WT and Ruan, XZ and Liu, BC and Ma, KL}, title = {GPR43 deficiency protects against podocyte insulin resistance in diabetic nephropathy through the restoration of AMPKα activity.}, journal = {Theranostics}, volume = {11}, number = {10}, pages = {4728-4742}, pmid = {33754024}, issn = {1838-7640}, abstract = {Rationale: Albuminuria is an early clinical feature in the progression of diabetic nephropathy (DN). Podocyte insulin resistance is a main cause of podocyte injury, playing crucial roles by contributing to albuminuria in early DN. G protein-coupled receptor 43 (GPR43) is a metabolite sensor modulating the cell signalling pathways to maintain metabolic homeostasis. However, the roles of GPR43 in podocyte insulin resistance and its potential mechanisms in the development of DN are unclear. Methods: The experiments were conducted by using kidney tissues from biopsied DN patients, streptozotocin (STZ) induced diabetic mice with or without global GPR43 gene knockout, diabetic rats treated with broad-spectrum oral antibiotics or fecal microbiota transplantation, and cell culture model of podocytes. Renal pathological injuries were evaluated by periodic acid-schiff staining and transmission electron microscopy. The expression of GPR43 with other podocyte insulin resistance related molecules was checked by immunofluorescent staining, real-time PCR, and Western blotting. Serum acetate level was examined by gas chromatographic analysis. The distribution of gut microbiota was measured by 16S ribosomal DNA sequencing with faeces. Results: Our results demonstrated that GPR43 expression was increased in kidney samples of DN patients, diabetic animal models, and high glucose-stimulated podocytes. Interestingly, deletion of GPR43 alleviated albuminuria and renal injury in diabetic mice. Pharmacological inhibition and knockdown of GPR43 expression in podocytes increased insulin-induced Akt phosphorylation through the restoration of adenosine 5'-monophosphate-activated protein kinase α (AMPKα) activity. This effect was associated with the suppression of AMPKα activity through post-transcriptional phosphorylation via the protein kinase C-phospholipase C (PKC-PLC) pathway. Antibiotic treatment-mediated gut microbiota depletion, and faecal microbiota transplantation from the healthy donor controls substantially improved podocyte insulin sensitivity and attenuated glomerular injury in diabetic rats accompanied by the downregulation of the GPR43 expression and a decrease in the level of serum acetate. Conclusion: These findings suggested that dysbiosis of gut microbiota-modulated GPR43 activation contributed to albuminuria in DN, which could be mediated by podocyte insulin resistance through the inhibition of AMPKα activity.}, }
@article {pmid33749411, year = {2021}, author = {Beyaz Coşkun, A and Sağdiçoğlu Celep, AG}, title = {Therapeutic modulation methods of gut microbiota and gut-liver axis.}, journal = {Critical reviews in food science and nutrition}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/10408398.2021.1902263}, pmid = {33749411}, issn = {1549-7852}, abstract = {Liver diseases are considered global health problems that cause more than 1 million deaths each year. Due to the increase in the prevalence of liver diseases worldwide, studies on different treatment methods have increased. Some of these methods is diagnostic and therapeutic applications based on the examination of the intestinal and intestinal microbiota. In this study, research articles, systematic review and review in the literature were examined in order to determine gut-liver axis relationship and treatment methods for liver diseases with gut modulation methods. Studies related to the subject have been searched in Google Scholar and Pubmed databases. The keywords "liver disease" and "gut-liver axis" and "microbiota" and "gut modulation methods" or "probiotic" or "prebiotic" or "symbiotic" or "antibiotic" or "bile acid regulation" or "adsorbent" or "fecal microbiota transplantation" were used in the searches. Improvements have been achieved in biomarkers of liver diseases by providing intestinal modulation with probiotic, prebiotic, symbiotic, antibiotic and adsorbents applications, bile acid regulation and fecal microbiota transplantation. In the results of experimental and clinical studies, it was seen that the therapeutic potential of the treatments performed by applying probiotics, prebiotics and symbiotics was higher.}, }
@article {pmid33748913, year = {2021}, author = {Tixier, EN and Verheyen, E and Luo, Y and Grinspan, LT and Du, CH and Ungaro, RC and Walsh, S and Grinspan, AM}, title = {Systematic Review with Meta-Analysis: Fecal Microbiota Transplantation for Severe or Fulminant Clostridioides difficile.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, pmid = {33748913}, issn = {1573-2568}, abstract = {BACKGROUND: Severe and fulminant Clostridioides difficile infection (CDI) is associated with significant morbidity and mortality. While fecal microbiota transplantation (FMT) has proved to be a highly effective treatment for recurrent CDI, its efficacy in severe or fulminant CDI remains uncertain.<br><br>AIMS: To perform a systematic review with meta-analysis evaluating clinical outcomes and safety of FMT in severe and fulminant CDI.<br><br>METHODS: A systemic review with meta-analysis was performed through comprehensive search of Embase, Medline (Ovid), trial registers, and conference abstracts through January 2020. Studies on FMT in severe and fulminant CDI were included. Meta-analysis was done with random effects models given heterogeneity to estimate rates of cure, mortality, and colectomy. Publication bias was assessed using Egger's test.<br><br>RESULTS: Sixteen studies comprised of one randomized controlled trial, four cohort studies, and eleven case series were analyzed. In total, 676 patients underwent FMT for severe or fulminant CDI. The overall rate of clinical cure after single FMT was 61.3% (95% CI 43.2-78.0%) with 10.9% (95% CI 0.2-30.2%) of patients experiencing major adverse events. The overall pooled colectomy rate after FMT was 8.2% (95% CI 0.1-23.7%) with a pooled all-cause mortality rate after FMT of 15.6% (95% CI 7.8-25.0%).<br><br>CONCLUSION: Low-quality data support the use of fecal microbiota transplantation in patients with severe and fulminant Clostridioides difficile infection.}, }
@article {pmid33744565, year = {2021}, author = {Chu, Q and Zhang, S and Yu, X and Wang, Y and Zhang, M and Zheng, X}, title = {Fecal microbiota transplantation attenuates nano-plastics induced toxicity in Caenorhabditis elegans.}, journal = {The Science of the total environment}, volume = {779}, number = {}, pages = {146454}, doi = {10.1016/j.scitotenv.2021.146454}, pmid = {33744565}, issn = {1879-1026}, mesh = {Animals ; *Caenorhabditis elegans ; Caenorhabditis elegans Proteins ; *Fecal Microbiota Transplantation ; Microplastics/*toxicity ; }, abstract = {Current studies simply focus on the toxicity of nano-plastics, while the correlation between their toxicity and bio-distribution, as well as intestinal microorganisms is still blank. Therefore, we systematically evaluated the toxicity based on the accumulation characteristics of nano-plastics in C. elegans. Meanwhile, for the first time, human fecal microbiota was transplanted into the gut of C. elegans and found that nano-plastics can through the intestinal barrier to the whole body after oral intake and can't be drastically excreted until die, thus causing toxic effects; while human fecal microbiota transplantation can significantly improve the living state via activating PMK-1/SKN-1 pathway to promote the production of intracellular glutathione, and exogenous glutathione addition can also markedly protect nematodes against nano-plastics induced toxicity. Our results not only provide a fully understand between the accumulation characteristic and health risk of nano-plastics, but also take C. elegans and intestinal flora into the field of toxicity evolution of nanomaterials.}, }
@article {pmid33742731, year = {2021}, author = {Rao, J and Xie, R and Lin, L and Jiang, J and Du, L and Zeng, X and Li, G and Wang, C and Qiao, Y}, title = {Fecal microbiota transplantation ameliorates gut microbiota imbalance and intestinal barrier damage in rats with stress-induced depressive-like behavior.}, journal = {The European journal of neuroscience}, volume = {53}, number = {11}, pages = {3598-3611}, doi = {10.1111/ejn.15192}, pmid = {33742731}, issn = {1460-9568}, mesh = {Animals ; Brain ; Depression/therapy ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Rats ; Stress, Psychological/therapy ; }, abstract = {The gut-microbiota-brain axis is the most important complex and bidirectional pathway between the gastrointestinal tract and the central nervous system. This study investigated the potential of microbe-induced gut-to-brain signaling to modulate the effect of stress on depressive-like behavior, intestinal barrier, and neuroinflammation. Result showed that fecal microbiota transplantation increased the consumption of sucrose solutions and decreased the immobility time in forced swimming test. This treatment also increased Firmicutes and decreased Bacteroidetes and Desulfobacterota at phylum levels; reduced the loss of villi and epithelial cells; suppressed the inflammatory cell infiltration in the ileum; increased the expression of ZO-1, occludin; protected the mucosal layer function; and suppressed the high levels of inflammasomes (NLRP3, ASC, caspase-1, and IL-1β) in rat brain. In summary, fecal microbiota transplantation improves the depressive-like behavior, alters the gut microbiota imbalance, and alleviates the intestinal tract inflammation, intestinal mucosa disruption, and neuroinflammation in rats induced by chronic unpredictable mild stress.}, }
@article {pmid33741982, year = {2021}, author = {Agranyoni, O and Meninger-Mordechay, S and Uzan, A and Ziv, O and Salmon-Divon, M and Rodin, D and Raz, O and Koman, I and Koren, O and Pinhasov, A and Navon-Venezia, S}, title = {Gut microbiota determines the social behavior of mice and induces metabolic and inflammatory changes in their adipose tissue.}, journal = {NPJ biofilms and microbiomes}, volume = {7}, number = {1}, pages = {28}, pmid = {33741982}, issn = {2055-5008}, abstract = {The link between the gut microbiota and social behavior has been demonstrated, however the translational impact of a certain microbiota composition on stable behavioral patterns is yet to be elucidated. Here we employed an established social behavior mouse model of dominance (Dom) or submissiveness (Sub). A comprehensive 16S rRNA gene sequence analysis of Dom and Sub mice revealed a significantly different gut microbiota composition that clearly distinguishes between the two behavioral modes. Sub mice gut microbiota is significantly less diverse than that of Dom mice, and their taxa composition uniquely comprised the genera Mycoplasma and Anaeroplasma of the Tenericutes phylum, in addition to the Rikenellaceae and Clostridiaceae families. Conversely, the gut microbiota of Dom mice includes the genus Prevotella of the Bacteriodetes phylum, significantly less abundant in Sub mice. In addition, Sub mice show lower body weight from the age of 2 weeks and throughout their life span, accompanied with lower epididymis white adipose tissue (eWAT) mass and smaller adipocytes together with substantially elevated expression of inflammation and metabolic-related eWAT adipokines. Finally, fecal microbiota transplantation into germ-free mice show that Sub-transplanted mice acquired Sub microbiota and adopted their behavioral and physiological features, including depressive-like and anti-social behaviors alongside reduced eWAT mass, smaller adipocytes, and a Sub-like eWAT adipokine profile. Our findings demonstrate the critical role of the gut microbiome in determining dominance vs. submissiveness and suggest an association between gut microbiota, the eWAT metabolic and inflammatory profile, and the social behavior mode.}, }
@article {pmid33738808, year = {2021}, author = {Xi, W and Gao, X and Zhao, H and Luo, X and Li, J and Tan, X and Wang, L and Zhao, JB and Wang, J and Yang, G and Liu, LY and Wang, YY and Peng, L and Zou, LP and Yang, Y}, title = {Depicting the composition of gut microbiota in children with tic disorders: an exploratory study.}, journal = {Journal of child psychology and psychiatry, and allied disciplines}, volume = {}, number = {}, pages = {}, doi = {10.1111/jcpp.13409}, pmid = {33738808}, issn = {1469-7610}, abstract = {BACKGROUND: Symptom improvement in children with tic disorder (TD) following fecal microbiota transplantation led us to investigate the gut microbiota in TD. This exploratory study aims to depict the gut microbial profile in patients with TD and explore the impact of dopamine receptor antagonist (DRA) drugs on the composition and metabolic function of the gut microbiota.<br><br>METHODS: The gut microbiota were profiled in fecal samples of 49 children with TD and 50 matched healthy controls (HC) using shotgun metagenomic sequencing. A random forest (RF) model was constructed using the gut bacterial species to distinguish TD from HC. Associations between clinical metadata and microbial abundance or function were analyzed using MaAsLin2 and Spearman correlation.<br><br>RESULTS: The gut microbiota in children with TD was featured by higher abundances of Bacteroides plebeius and Ruminococcus lactaris (a potential pro-inflammatory taxon) and lower abundances of Prevotella stercorea and Streptococcus lutetiensis compared to HC. The constructed RF model accurately distinguished TD from HC based on the gut microbiota profile, resulting in an AUC of 0.884. Significant correlations were observed between tic symptom severity and the abundances of multiple bacterial species and gut microbiota metabolic functions. Multivariate analysis identified an upregulation of 4-aminobutanoate (GABA) degradation in the gut microbiota associated with TD status. The gut microbiota of DRA-treated TD children showed a distinct gut microbiota compared to the treatment-naïve group, represented by an increase in some potential enteric pathogens such as Escherichia coli, a decline in several species including Akkermansia muciniphila, and alterations in various metabolic functions.<br><br>CONCLUSIONS: Bacterial species promoting inflammatory responses and those modulating neurotransmitters such as GABA may be involved in the pathogenesis of TD. The use of DRA drugs is likely to induce overgrowth of some enteric pathogens and alter the gut microbiota metabolism.}, }
@article {pmid33734496, year = {2021}, author = {Li, H and Zhuang, P and Zhang, Y and Shou, Q and Lu, Y and Wang, G and Qiu, J and Wang, J and He, L and Chen, J and Jiao, J}, title = {Mixed conjugated linoleic acid sex-dependently reverses high-fat diet-induced insulin resistance via the gut-adipose axis.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {35}, number = {4}, pages = {e21466}, doi = {10.1096/fj.202002161RR}, pmid = {33734496}, issn = {1530-6860}, mesh = {Adipose Tissue/*metabolism ; Animals ; Body Weight/drug effects ; *Diet, High-Fat ; Gastrointestinal Microbiome/*drug effects/physiology ; Insulin Resistance/*physiology ; Linoleic Acids, Conjugated/*pharmacology ; Lipid Metabolism/drug effects ; Mice, Inbred C57BL ; Obesity/metabolism ; }, abstract = {Conjugated linoleic acid (CLA) may prevent the development of obesity and metabolic disorders. However, the effects of CLA on inflammation and glucose metabolism are controversial. The underlying mechanisms governing the gut microbiota and sexual dimorphisms have also not been elucidated. The present study assessed the effect of CLA on glucose and lipid metabolism in established obesity and examined the mechanism of action based on gut microbiota. Four-week-old C57BL/6J mice were fed a high-fat diet (HFD) for 10 weeks to induce obesity. The diet-induced obese (DIO) mice were fed an HFD supplemented with mixed CLA (50% cis-9, trans-11 isomer and 50% trans-10, cis-12 isomers, 0.2% wt/wt) for 15 weeks. CLA supplementation remarkably reversed body weight in both sexes. CLA favored anti-inflammatory microbiota in male mice, mediating increased short-chain fatty acids and decreased lipopolysaccharide (LPS) production, which alleviated global inflammation and improved insulin sensitivity via inhibition of the TLR4-NF-κB pathway in adipose tissue. CLA promoted the growth of hydrogen sulfide-producing Desulfovibrio and the release of LPS in female mice, which aggravated adipose inflammation and insulin resistance. Although CLA impaired glucose metabolism in females, brown adipose tissue was significantly activated with browning of white adipose tissue in both sexes, which led to enhanced energy expenditure. Fecal transplantation from CLA-treated mice to DIO mice mimicked the sex-dependent phenotype. In conclusion, CLA decreased body weight and increased energy expenditure but sex-dependently modulated insulin resistance via the gut-adipose axis.}, }
@article {pmid33727402, year = {2021}, author = {Jin, G and Tang, Q and Ma, J and Liu, X and Zhou, B and Sun, Y and Pang, X and Guo, Z and Xie, R and Liu, T and Wang, B and Cao, H}, title = {Maternal Emulsifier P80 Intake Induces Gut Dysbiosis in Offspring and Increases Their Susceptibility to Colitis in Adulthood.}, journal = {mSystems}, volume = {6}, number = {2}, pages = {}, pmid = {33727402}, issn = {2379-5077}, abstract = {Early life events can lead to multiple diseases in adulthood. Previous studies suggested that polysorbate 80 (P80) as a widely used emulsifier in pharmaceutical formulations and food industries could impair the intestinal barrier. However, whether maternal P80 (MP80) exposure could affect the long-term health of offspring remains unknown. In this study, we found that maternal P80 intake could retard intestinal development, disrupt the intestinal barrier, and cause low-grade intestinal inflammation in 3-week-old offspring. 16S rRNA sequencing and correlation analysis revealed that Mucispirillum, Clostridium XI, and Parabacteroides, which positively correlated with intestinal proliferation and differentiation, were decreased in the maternal P80 group. Interestingly, the increase in some harmful bacteria, including Proteobacteria, Helicobacteraceae, Campylobacterales, and Desulfovibrionales, persisted from the weaning period to adulthood (3 to 8 weeks). Furthermore, a fecal microbiota transplantation assay showed that the mice gavaged with feces from 3-week-old offspring of the MP80 group presented more severe intestinal inflammation and barrier disruption than the mice that received feces from the offspring of the control group. Finally, maternal P80 intake remarkably aggravated the structural disorder of intestinal crypt, increased proinflammatory factors, and exacerbated dextran sulfate sodium (DSS)-induced colitis in adulthood. Conclusively, maternal P80 intake could induce gut dysbiosis and promote colitis susceptibility in adulthood. This study provides new insights into the prevention of inflammatory bowel disease (IBD).IMPORTANCE The main findings of this research showed that maternal P80 intake could disrupt the intestinal barrier, induce gut dysbiosis, and promote colitis susceptibility in adulthood. This study will enhance understanding of the prevention of IBD.}, }
@article {pmid33723543, year = {2021}, author = {Gilca-Blanariu, GE and Stefanescu, G and Girleanu, I and Iqbal, T and Segal, J and Mullish, B and Quraishi, MN and Keller, J and Molnar, T and Megraud, F and Dumitrascu, D and Manuc, M and Iancu, LS and Marica, C and Gheorghe, C and Manzoor, S and Trifan, A}, title = {Romanian National Guideline on Translating Fecal Microbiota Transplantation Applications related to Clostridioides difficile Infections into the Local Clinical Practice.}, journal = {Journal of gastrointestinal and liver diseases : JGLD}, volume = {30}, number = {1}, pages = {147-163}, doi = {10.15403/jgld-3297}, pmid = {33723543}, issn = {1842-1121}, abstract = {Fecal microbiota transplantation involves the infusion of intestinal microorganisms via the transfer of a stool from a healthy individual into a diseased individual, with the intent of restoring normal intestinal flora. Fecal transplant is proposed for the treatment of refractory Clostridioides difficile infection. At present, recurrent Clostridioides difficile infection is the only indication supported by solid scientific evidence. Regulations by healthcare authorities vary among different countries. Considering that Romania does not have an available national guideline to offer standardization, this paper aimed to create a national fecal microbiota transplantation guideline concerning indications, techniques and donor screening, developed by international and local scientific working groups.}, }
@article {pmid33722710, year = {2021}, author = {Alghetaa, H and Mohammed, A and Zhou, J and Singh, N and Nagarkatti, M and Nagarkatti, P}, title = {Resveratrol-mediated attenuation of superantigen-driven acute respiratory distress syndrome is mediated by microbiota in the lungs and gut.}, journal = {Pharmacological research}, volume = {167}, number = {}, pages = {105548}, doi = {10.1016/j.phrs.2021.105548}, pmid = {33722710}, issn = {1096-1186}, support = {P01 AT003961/AT/NCCIH NIH HHS/United States ; P20 GM103641/GM/NIGMS NIH HHS/United States ; R01 AT006888/AT/NCCIH NIH HHS/United States ; R01 ES030144/ES/NIEHS NIH HHS/United States ; R01 AI123947/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Anti-Inflammatory Agents/*pharmacology ; Cell Line ; Colon/*drug effects/immunology/metabolism/microbiology ; Cytokines/metabolism ; Disease Models, Animal ; Dysbiosis ; *Enterotoxins ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*drug effects ; Inflammation Mediators/metabolism ; Lactobacillus reuteri/drug effects/growth &amp; development ; Lung/*drug effects/immunology/metabolism/microbiology ; Mice, Inbred C3H ; Respiratory Distress Syndrome/immunology/metabolism/microbiology/*prevention &amp; control ; Resveratrol/*pharmacology ; *Superantigens ; }, abstract = {Acute Respiratory Distress Syndrome (ARDS) is triggered by a variety of agents, including Staphylococcal Enterotoxin B (SEB). Interestingly, a significant proportion of patients with COVID-19, also develop ARDS. In the absence of effective treatments, ARDS results in almost 40% mortality. Previous studies from our laboratory demonstrated that resveratrol (RES), a stilbenoid, with potent anti-inflammatory properties can attenuate SEB-induced ARDS. In the current study, we investigated the role of RES-induced alterations in the gut and lung microbiota in the regulation of ARDS. Our studies revealed that SEB administration induced inflammatory cytokines, ARDS, and 100% mortality in C3H/HeJ mice. Additionally, SEB caused a significant increase in pathogenic Proteobacteria phylum and Propionibacterium acnes species in the lungs. In contrast, RES treatment attenuated SEB-mediated ARDS and mortality in mice, and significantly increased probiotic Actinobacteria phylum, Tenericutes phylum, and Lactobacillus reuteri species in both the colon and lungs. Colonic Microbiota Transplantation (CMT) from SEB-injected mice that were treated with RES as well as the transfer of L. reuteri into recipient mice inhibited the production of SEB-mediated induction of pro-inflammatory cytokines such as IFN-γ and IL-17 but increased that of anti-inflammatory IL-10. Additionally, such CMT and L. reuteri recipient mice exposed to SEB, showed a decrease in lung-infiltrating mononuclear cells, cytotoxic CD8+ T cells, NKT cells, Th1 cells, and Th17 cells, but an increase in the population of regulatory T cells (Tregs) and Th3 cells, and increase in the survival of mice from SEB-mediated ARDS. Together, the current study demonstrates that ARDS induced by SEB triggers dysbiosis in the lungs and gut and that attenuation of ARDS by RES may be mediated, at least in part, by alterations in microbiota in the lungs and the gut, especially through the induction of beneficial bacteria such as L. reuteri.}, }
@article {pmid33722220, year = {2021}, author = {Tang, X and Wang, W and Hong, G and Duan, C and Zhu, S and Tian, Y and Han, C and Qian, W and Lin, R and Hou, X}, title = {Gut microbiota-mediated lysophosphatidylcholine generation promotes colitis in intestinal epithelium-specific Fut2 deficiency.}, journal = {Journal of biomedical science}, volume = {28}, number = {1}, pages = {20}, pmid = {33722220}, issn = {1423-0127}, support = {81330014//National Natural Science Foundation of China/ ; 81974068//National Natural Science Foundation of China/ ; 81900580//National Natural Science Foundation of China/ ; 81800467//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND AND AIMS: Previous study disclosed Fucosyltransferase 2 (Fut2) gene as a IBD risk locus. This study aimed to explore the mechanism of Fut2 in IBD susceptibility and to propose a new strategy for the treatment of IBD.<br><br>METHODS: Intestinal epithelium-specific Fut2 knockout (Fut2△IEC) mice was used. Colitis was induced by dextran sulfate sodium (DSS). The composition and diversity of gut microbiota were assessed via 16S rRNA analysis and the metabolomic findings was obtained from mice feces via metabolite profiling. The fecal microbiota transplantation (FMT) experiment was performed to confirm the association of gut microbiota and LPC. WT mice were treated with Lysophosphatidylcholine (LPC) to verify its impact on colitis.<br><br>RESULTS: The expression of Fut2 and α-1,2-fucosylation in colonic tissues were decreased in patients with UC (UC vs. control, P = 0.036) and CD (CD vs. control, P = 0.031). When treated with DSS, in comparison to WT mice, more severe intestinal inflammation and destructive barrier functions in Fut2△IEC mice was noted. Lower gut microbiota diversity was observed in Fut2△IEC mice compared with WT mice (p < 0.001). When exposed to DSS, gut bacterial diversity and composition altered obviously in Fut2△IEC mice and the fecal concentration of LPC was increased. FMT experiment revealed that mice received the fecal microbiota from Fut2△IEC mice exhibited more severe colitis and higher fecal LPC concentration. Correlation analysis showed that the concentration of LPC was positively correlated with four bacteria-Escherichia, Bilophila, Enterorhabdus and Gordonibacter. Furthermore, LPC was proved to promote the release of pro-inflammatory cytokines and damage epithelial barrier in vitro and in vivo.<br><br>CONCLUSION: Fut2 and α-1,2-fucosylation in colon were decreased not only in CD but also in UC patients. Gut microbiota in Fut2△IEC mice is altered structurally and functionally, promoting generation of LPC which was proved to promote inflammation and damage epithelial barrier.}, }
@article {pmid33718398, year = {2021}, author = {Delli Bovi, AP and Marciano, F and Mandato, C and Siano, MA and Savoia, M and Vajro, P}, title = {Oxidative Stress in Non-alcoholic Fatty Liver Disease. An Updated Mini Review.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {595371}, pmid = {33718398}, issn = {2296-858X}, abstract = {Non-alcoholic fatty liver disease (NAFLD) is a challenging disease caused by multiple factors, which may partly explain why it remains still orphan of an adequate therapeutic strategy. Herein we focus on the interplay between oxidative stress (OS) and the other causal pathogenetic factors. Different reactive oxygen species (ROS) generators contribute to NAFLD inflammatory and fibrotic progression, which is quite strictly linked to the lipotoxic liver injury from fatty acids and/or a wide variety of their biologically active metabolites in the context of either a two-hit or a (more recent) multiple parallel hits theory. An antioxidant defense system is usually able to protect hepatic cells from damaging effects caused by ROS, including those produced into the gastrointestinal tract, i.e., by-products generated by usual cellular metabolic processes, normal or dysbiotic microbiota, and/or diet through an enhanced gut-liver axis. Oxidative stress originating from the imbalance between ROS generation and antioxidant defenses is under the influence of individual genetic and epigenetic factors as well. Healthy diet and physical activity have been shown to be effective on NAFLD also with antioxidant mechanisms, but compliance to these lifestyles is very low. Among several considered antioxidants, vitamin E has been particularly studied; however, data are still contradictory. Some studies with natural polyphenols proposed for NAFLD prevention and treatment are encouraging. Probiotics, prebiotics, diet, or fecal microbiota transplantation represent new therapeutic approaches targeting the gut microbiota dysbiosis. In the near future, precision medicine taking into consideration genetic or environmental epigenetic risk factors will likely assist in further selecting the treatment that could work best for a specific patient.}, }
@article {pmid33718277, year = {2021}, author = {Żebrowska, P and Łaczmańska, I and Łaczmański, Ł}, title = {Future Directions in Reducing Gastrointestinal Disorders in Children With ASD Using Fecal Microbiota Transplantation.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {630052}, pmid = {33718277}, issn = {2235-2988}, mesh = {*Autism Spectrum Disorder ; Child ; Fecal Microbiota Transplantation ; *Gastrointestinal Diseases ; *Gastrointestinal Microbiome ; Humans ; *Inflammatory Bowel Diseases ; }, abstract = {Research on the use of fecal microbiota transplantation (FMT) in the treatment of disorders related to digestive system ailments in children with autism spectrum disorders (ASDs) is a new attempt in a therapeutic approach. There are very little scientific evidences available on this emerging alternative method. However, it appears to be interesting not only because of its primary outcome, relieving the gastrointestinal (GI) symptoms, but also secondary therapeutic effect of alleviating autistic behavioral symptoms. FMT seems to be also promising method in the treatment of another group of pediatric patients, children with inflammatory bowel disease (IBD). The aim of this study is to discuss the potential use of FMT and modified protocols (MTT, microbiota transfer therapy) in the treatment of GI disorders in ASD children supported by reports on another disease, IBD concerning pediatric patients. Due to the few reports of the use of FMT in the treatment of children, these two patients groups were selected, although suffering from distant health conditions: neurodevelopmental disorder and gastrointestinal tract diseases, because of the the fact that they seem related in aspects of the presence of GI symptoms, disturbed intestinal microbiota, unexplained etiology of the condition and age range of patients. Although the outcomes for all are promising, this type of therapy is still an under-researched topic, studies in the group of pediatric patients are sparse, also there is a high risk of transmission of infectious and noninfectious elements during the procedure and no long-term effects on global health are known. For those reasons all obtained results should be taken with a great caution. However, in the context of future therapeutic directions for GI observed in neurodevelopmental disorders and neurodegenerative diseases, the topic seems worthy of attention.}, }
@article {pmid33713592, year = {2021}, author = {Cortés, P and Bi, Y and Stancampiano, F and Valery, JR and Cooper, JH and Harris, DM}, title = {Clostridioides Difficile Infection: A comprehensive review for primary providers.}, journal = {Romanian journal of internal medicine = Revue roumaine de medecine interne}, volume = {}, number = {}, pages = {}, doi = {10.2478/rjim-2021-0010}, pmid = {33713592}, issn = {2501-062X}, abstract = {Clostridioides Difficile infection (CDI) is an issue of great concern due to its rising incidence, recurrence, morbidity and impact on healthcare spending. Treatment guidelines have changed in the last few years, and new therapies are being considered. This is a practical review for the primary care practitioner of the latest guidelines for CDI diagnosis, treatment and emerging therapies.}, }
@article {pmid33711509, year = {2021}, author = {Qian, XH and Song, XX and Liu, XL and Chen, SD and Tang, HD}, title = {Inflammatory pathways in Alzheimer's disease mediated by gut microbiota.}, journal = {Ageing research reviews}, volume = {68}, number = {}, pages = {101317}, doi = {10.1016/j.arr.2021.101317}, pmid = {33711509}, issn = {1872-9649}, mesh = {*Alzheimer Disease/therapy ; Amyloid ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Probiotics/therapeutic use ; }, abstract = {In the past decade, numerous studies have demonstrated the close relationship between gut microbiota and the occurrence and development of Alzheimer's disease (AD). However, the specific mechanism is still unclear. Both the neuroinflammation and systemic inflammation serve as the key hubs to accelerate the process of AD by promoting pathology and damaging neuron. What's more, the gut microbiota is also crucial for the regulation of inflammation. Therefore, this review focused on the role of gut microbiota in AD through inflammatory pathways. Firstly, this review summarized the relationship and interaction among gut microbiota, inflammation, and AD. Secondly, the direct and indirect regulatory effects of gut microbiota on AD through inflammatory pathways were described. These effects were mainly mediated by the component of the gut microbiota (lipopolysaccharides (LPS) and amyloid peptides), the metabolites of bacteria (short-chain fatty acids, branched amino acids, and neurotransmitters) and functional by-products (bile acids). In addition, potential treatments (fecal microbiota transplantation, antibiotics, probiotics, prebiotics, and dietary interventions) for AD were also discussed through these mechanisms. Finally, according to the current research status, the key problems to be solved in the future studies were proposed.}, }
@article {pmid33711435, year = {2021}, author = {Long, D and Liu, M and Li, H and Song, J and Jiang, X and Wang, G and Yang, X}, title = {Dysbacteriosis induces abnormal neurogenesis via LPS in a pathway requiring NF-κB/IL-6.}, journal = {Pharmacological research}, volume = {167}, number = {}, pages = {105543}, doi = {10.1016/j.phrs.2021.105543}, pmid = {33711435}, issn = {1096-1186}, abstract = {In this study, we identified elevated levels of LPS and suppressed neurogenesis in a successfully established mouse model of gut microbiota dysbiosis. We mimicked these phenotypes using mouse and chicken embryos exposed to LPS and found that dramatic variation in gene expression was due to changes in the dorsal-ventral patterning of the neural tube. Cell survival and excess ROS were also involved in this process. Antioxidant administration alleviated LPS-activated NF-κB signaling, while directly blocking NF-κB signaling altered the LPS-induced inhibition of neurogenesis. Furthermore, IL-6 was proven to play a vital role in the expression of crucial neurogenesis-related genes and NF-κB. In summary, we found that the suppression of neurogenesis induced by dysbacteriosis-derived LPS was significantly reversed in mice with fecal microbiota transplantation. This study reveals that gut dysbacteriosis-derived LPS impairs embryonic neurogenesis, and that the NF-κB/IL-6 pathway could be one of the main factors triggering the downstream signaling cascade.}, }
@article {pmid33708514, year = {2021}, author = {Song, A and Shen, N and Gan, C and Luo, C and Luo, C and Wang, J and Cao, Q and Chen, J}, title = {Exploration of the relationship between intestinal flora changes and gut acute graft-versus-host disease after hematopoietic stem cell transplantation.}, journal = {Translational pediatrics}, volume = {10}, number = {2}, pages = {283-295}, pmid = {33708514}, issn = {2224-4344}, abstract = {Background: Acute graft-versus-host disease (aGVHD) is a life-threatening factor for post-hematopoietic stem cell transplantation (HSCT) patients. To investigate the relationship between intestinal flora changes and gut aGVHD after HSCT, we performed this cross-sectional study.<br><br>Methods: We selected children from our medical center from July 2016 to January 2017. Fifty-six samples from 42 patients and 6 samples from normal children met the study criteria and were analyzed. Fecal 16S RNA sequencing was completed before transplantation or on days 7, 28 or 100 post-transplantation. The intestinal infection and GVHD clinical data were retrospectively analyzed, and the survival risk factors were analyzed. Correlation analysis was performed with the feces bioinformatic data.<br><br>Results: The GVHD group alpha diversity was the lowest, which was significantly different than that of the non-diarrhea group (P value=0.032). A richer posttransplantation relative abundance of Moraxellaceae was conducive to survival, while that of Enterococcaceae and Alphaproteobacteria was not. Similarly, a rich relative abundance of Proteobacteria, Gammaproteobacteria and Odoribacteraceae in the intestinal flora before HSCT contributed to patient death thereafter. Regarding diarrhea, the GVHD group exhibited a richer Pasteurellales and Pasteurellaceae relative abundances, which showed strong correlations with diarrhea severity. Peptostreptococcaceae, Bifidobacteriales and Bifidobacteriaceae were richer in relative abundance in the intestinal infection group and correlated with pretransplant characteristics.<br><br>Conclusions: The gut microbiota diversity was lowest when gut aGVHD occurred, which was consistent with the clinically higher mortality rate and greater treatment difficulty. Pasteurellaceae played an important role in gut aGVHD and diarrhea severity. Bifidobacteriaceae led to infectious diarrhea after HSCT. Specific bacteria were biomarkers for survival: Moraxellaceae, Enterococcaceae and Alphaproteobacteria from the intestinal flora after HSCT and Proteobacteria, Gammaproteobacteria and Odoribacteraceae before HSCT.}, }
@article {pmid33708182, year = {2021}, author = {Su, Y and Li, X and Li, D and Sun, J}, title = {Fecal Microbiota Transplantation Shows Marked Shifts in the Multi-Omic Profiles of Porcine Post-weaning Diarrhea.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {619460}, pmid = {33708182}, issn = {1664-302X}, abstract = {Weaning is the most critical phase in pig production and is generally associated with significant impacts on intestinal morphology, structure, physiology, and immune responses, which can lead to subsequent production inefficiencies such as decreases in growth and intake and increases in morbidity and mortality. In the present study, we attempted to explore the effects of fecal microbiota transplantation (FMT) on the fecal microbiota, fecal metabolites, and transcriptome in the jejunum, colon, liver, spleen, and oral mucosa in piglets with post-weaning diarrhea and to evaluate the therapeutic potential of FMT in piglets with post-weaning diarrhea. We found that FMT partially relieved the symptoms of diarrhea in piglets, and microbiota analysis results indicated that unclassified_f_Prevotellaceae was identified as an FMT-associated bacterial family at 66 day and that the Shannon index in the healthy group at 34, 38, and 66 days were higher than that at 21 day. Functional enrichment analysis of the oral mucosa, liver, jejunum, and colon showed that most of the differentially expressed genes (DEGs) were enriched in the terms metabolic process, immune response, and inflammatory response. Moreover, the enriched fecal metabolites focused mostly on apoptosis, beta-alanine metabolism, glutathione metabolism, and sphingolipid metabolism. We tried to detect specific "metabolite-bacterium" pairs, such as "g_Catenisphaera-stigmastentriol," "p_Bacteroidetes-(6beta,22E)-6-hydroxystigmasta-4,22-dien-3-one," and "g_Prevotellaceae_NK3B31_group-stenocereol." Overall, the present study provides a theoretical basis for the alleviation of weaning stress and contributes to the realization of effective and sustainable application of FMT in the pig production industry in the future.}, }
@article {pmid33705752, year = {2021}, author = {Wang, G and Hu, YX and He, MY and Xie, YH and Su, W and Long, D and Zhao, R and Wang, J and Dai, C and Li, H and Si, ZP and Cheng, X and Li, RM and Li, Z and Yang, X}, title = {Gut-Lung Dysbiosis Accompanied by Diabetes Mellitus Leads to Pulmonary Fibrotic Change through the NF-κB Signaling Pathway.}, journal = {The American journal of pathology}, volume = {191}, number = {5}, pages = {838-856}, doi = {10.1016/j.ajpath.2021.02.019}, pmid = {33705752}, issn = {1525-2191}, mesh = {Animals ; Anti-Infective Agents/administration &amp; dosage ; Diabetes Mellitus, Experimental/chemically induced/*complications/pathology ; Disease Models, Animal ; Dysbiosis/chemically induced/*complications/pathology/therapy ; Fecal Microbiota Transplantation ; Flavonoids/administration &amp; dosage ; Gastrointestinal Microbiome ; Intestines/microbiology/pathology ; Lincomycin/adverse effects ; Lung/microbiology/pathology ; Mice ; Mice, Inbred C57BL ; *Microbiota ; NF-kappa B/genetics/*metabolism ; Pulmonary Fibrosis/etiology/*microbiology/pathology/therapy ; *Signal Transduction ; Streptozocin/adverse effects ; }, abstract = {Growing evidence shows that the lungs are an unavoidable target organ of diabetic complications. However, the pathologic mechanisms of diabetic lung injury are still controversial. This study demonstrated the dysbiosis of the gut and lung microbiome, pulmonary alveolar wall thickening, and fibrotic change in streptozotocin-induced diabetic mice and antibiotic-induced gut dysbiosis mice compared with controls. In both animal models, the NF-κB signaling pathway was activated in the lungs. Enhanced pulmonary alveolar well thickening and fibrotic change appeared in the lungs of transgenic mice expressing a constitutively active NF-κB mutant compared with wild type. When lincomycin hydrochloride-induced gut dysbiosis was ameliorated by fecal microbiota transplant, enhanced inflammatory response in the intestine and pulmonary fibrotic change in the lungs were significantly decreased compared with lincomycin hydrochloride-treated mice. Furthermore, the application of fecal microbiota transplant and baicalin could also redress the microbial dysbiosis of the gut and lungs in streptozotocin-induced diabetic mice. Taken together, these data suggest that multiple as yet undefined factors related to microbial dysbiosis of gut and lungs cause pulmonary fibrogenesis associated with diabetes mellitus through an NF-κB signaling pathway.}, }
@article {pmid33704807, year = {2021}, author = {Koretz, RL}, title = {JPEN Journal Club 61. Testing hypotheses.}, journal = {JPEN. Journal of parenteral and enteral nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1002/jpen.2099}, pmid = {33704807}, issn = {1941-2444}, }
@article {pmid33704802, year = {2021}, author = {Gu, M and Samuelson, DR and Taylor, CM and Molina, PE and Luo, M and Siggins, RW and Shellito, JE and Welsh, DA}, title = {Alcohol-associated intestinal dysbiosis alters mucosal-associated invariant T-cell phenotype and function.}, journal = {Alcoholism, clinical and experimental research}, volume = {45}, number = {5}, pages = {934-947}, pmid = {33704802}, issn = {1530-0277}, support = {P60 AA009803/AA/NIAAA NIH HHS/United States ; K99-AA026336/AA/NIAAA NIH HHS/United States ; R21 AA027199/AA/NIAAA NIH HHS/United States ; K99 AA026336/AA/NIAAA NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; U54- GM104940/GM/NIGMS NIH HHS/United States ; R24 AA019661/AA/NIAAA NIH HHS/United States ; UH2 AA026226/AA/NIAAA NIH HHS/United States ; }, abstract = {BACKGROUND: Chronic alcohol consumption is associated with a compromised innate and adaptive immune responses to infectious disease. Mucosa-associated invariant T (MAIT) cells play a critical role in antibacterial host defense. However, whether alcohol-associated deficits in innate and adaptive immune responses are mediated by alterations in MAIT cells remains unclear.<br><br>METHODS: To investigate the impact of alcohol on MAIT cells, mice were treated with binge-on-chronic alcohol for 10 days and sacrificed at day 11. MAIT cells in the barrier organs (lung, liver, and intestine) were characterized by flow cytometry. Two additional sets of animals were used to examine the involvement of gut microbiota on alcohol-induced MAIT cell changes: (1) Cecal microbiota from alcohol-fed (AF) mice were adoptive transferred into antibiotic-pretreated mice and (2) AF mice were treated with antibiotics during the experiment. MAIT cells in the barrier organs were measured via flow cytometry.<br><br>RESULTS: Binge-on-chronic alcohol feeding led to a significant reduction in the abundance of MAIT cells in the barrier tissues. However, CD69 expression on tissue-associated MAIT cells was increased in AF mice compared with pair-fed (PF) mice. The expression of Th1 cytokines and the corresponding transcriptional factor was tissue specific, showing downregulation in the intestine and increases in the lung and liver in AF animals. Transplantation of fecal microbiota from AF mice resulted in a MAIT cell profile aligned to that of AF mouse donor. Antibiotic treatment abolished the MAIT cell differences between AF and PF animals.<br><br>CONCLUSION: MAIT cells in the intestine, liver, and lung are perturbed by alcohol use and these changes are partially attributable to alcohol-associated dysbiosis. MAIT cell dysfunction may contribute to alcohol-induced innate and adaptive immunity and consequently end-organ pathophysiology.}, }
@article {pmid33694229, year = {2021}, author = {Rode, AA and Chehri, M and Krogsgaard, LR and Heno, KK and Svendsen, AT and Ribberholt, I and Helms, M and Engberg, J and Schønning, K and Tvede, M and Andersen, CØ and Jensen, US and Petersen, AM and Bytzer, P}, title = {Randomised clinical trial: a 12-strain bacterial mixture versus faecal microbiota transplantation versus vancomycin for recurrent Clostridioides difficile infections.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {53}, number = {9}, pages = {999-1009}, doi = {10.1111/apt.16309}, pmid = {33694229}, issn = {1365-2036}, mesh = {Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; Feces ; Humans ; Recurrence ; Treatment Outcome ; Vancomycin/therapeutic use ; }, abstract = {BACKGROUND: A defined bacterial mixture could be a safer alternative to faecal microbiota transplantation (FMT).<br><br>AIMS: To compare the efficacy of a 12-strain mixture termed rectal bacteriotherapy with either FMT or vancomycin for recurrent Clostridioides difficile infection (CDI) in an open-label 3-arm randomised controlled trial.<br><br>METHODS: We screened all individuals positive for C difficile from May 2017 to March 2019. Persons with laboratory-confirmed recurrent CDI were included. Before FMT and rectal bacteriotherapy, we pre-treated with vancomycin for 7-14 days. Rectal bacteriotherapy was applied by enema on three consecutive days and FMT by enema once with possible repetition for two to three infusions within 14 days. The vancomycin group was treated for 14 days with additional five weeks of tapering for multiple recurrences. The primary outcome was clinical cure within 90 days. A secondary outcome was 180-day all-cause mortality.<br><br>RESULTS: Participants in the FMT group (n = 34) were cured more often than participants receiving vancomycin (n = 31), 76% vs 45% (OR 3.9 (1.4-11.4), P < 0.01) or rectal bacteriotherapy (n = 31), 76% vs 52% (OR 3.0 (1.1-8.8), P = 0.04). Rectal bacteriotherapy and vancomycin performed similarly (P = 0.61). The mortality rate was 6% in the FMT group, 13% in the bacteriotherapy group and 23% in the vancomycin group. FMT tended to reduce mortality compared with vancomycin, OR 0.2 (0.04-1.12), P = 0.07.<br><br>CONCLUSIONS: Rectal bacteriotherapy appears as effective as vancomycin but less effective than 1-3 FMTs. FMT by enema with 1-3 infusions is superior to vancomycin for treating recurrent C difficile infections and might reduce mortality.}, }
@article {pmid33692965, year = {2021}, author = {Kaiser, T and Nalluri, H and Zhu, Z and Staley, C}, title = {Donor Microbiota Composition and Housing Affect Recapitulation of Obese Phenotypes in a Human Microbiota-Associated Murine Model.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {614218}, pmid = {33692965}, issn = {2235-2988}, support = {R01 DK122056/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Feces ; *Housing ; Humans ; Mice ; *Microbiota ; Obesity ; Phenotype ; }, abstract = {Human microbiota-associated (HMA) mouse models offer a valuable approach to study the role of intestinal microbiota in the development of obesity. In this study, we used an HMA model to evaluate whether engraftment of human obese or lean microbiota, from each of three donors, could recapitulate host phenotypes under conventional and specific-pathogen-free housing. Microbiota engraftment was correlated with donor relative abundances of the class Bacteroidia (Spearman's ρ = 0.73, P ≤ 0.001), and one obese donor resulted in significant weight gain (P ≤ 0.003) and compromised insulin sensitivity under conventional housing. SPF housing partially blunted phenotypic response. Results of this study indicate that our HMA model partially recapitulates obese phenotypes under conventional housing and highlights a need to consider donor-specific effects as well as housing conditions when studying the role of the microbiota in obesity.}, }
@article {pmid33692964, year = {2021}, author = {Liu, J and Xu, Y and Jiang, B}, title = {Novel Insights Into Pathogenesis and Therapeutic Strategies of Hepatic Encephalopathy, From the Gut Microbiota Perspective.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {586427}, pmid = {33692964}, issn = {2235-2988}, mesh = {Brain ; Dysbiosis/therapy ; *Gastrointestinal Microbiome ; *Hepatic Encephalopathy/therapy ; Humans ; *Probiotics/therapeutic use ; }, abstract = {Since the 1950s, gradual changes in the gut microbiota of patients with hepatic encephalopathy have been observed. Previous research has indicated potential associations between the gut and brain, and the gut microbiota is becoming a hot topic in research on diseases of the nervous system. However, for the past few decades, studies of hepatic encephalopathy have been restricted to controlling the gut microbiota during macroscopic manipulation, such as probiotic intervention, while its clinical use remains controversial, and the cellular mechanisms underlying this condition are still poorly understood. This thesis seeks to comprehensively understand and explain the role of gut microbiota in hepatic encephalopathy as well as analyze the effects of intervention by regulating the gut microbiota. Evidence is presented that shows that dysbiosis of the gut microbiota is the primary pathological driver of hepatic encephalopathy and impacts pathologic progression via complex regulatory networks. As a result, suggestions were identified for future mechanistic research and improvements in therapeutic strategies for hepatic encephalopathy.}, }
@article {pmid33682170, year = {2021}, author = {Gupta, S and Zhu, J and McCarty, TR and Pruce, J and Kassam, Z and Kelly, C and Fischer, M and Allegretti, JR}, title = {Cost-effectiveness analysis of sequential fecal microbiota transplantation for fulminant Clostridioides difficile infection.}, journal = {Journal of gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgh.15483}, pmid = {33682170}, issn = {1440-1746}, support = {T32DK007533-35/DK/NIDDK NIH HHS/United States ; }, abstract = {BACKGROUND AND AIM: Fulminant Clostridioides difficile infections (FCDI) account for 8% of cases and substantial healthcare burden. Fecal microbiota transplantation is recommended for recurrent CDI, but emerging data support use for FCDI. We aimed to assess the cost-effectiveness of a sequential fecal microbiota transplantation (sFMT) protocol for FCDI compared with current standard therapy.<br><br>METHODS: A Markov model simulated patients with FCDI in a 1-year time horizon. The treatment algorithm for up to three sFMTs, clinical probabilities, and direct costs were used from published sources. Outcomes were quality-adjusted life years (QALYs) and costs. The healthcare sector perspective was used with a willingness-to-pay threshold of $100 000 per QALY.<br><br>RESULTS: Sequential fecal microbiota transplantation (FMT) for FCDI was associated with lower overall cost ($28 309 vs $33 980) and higher QALY (0.765 vs 0.686) compared with standard therapy. sFMT is cost-effective in 100% of iterations. sFMT remained cost-effective at cure rates > 44.8% for the first FMT and at stool preparation cost < $6944 per instillation. We find a wide range of efficacies for the first versus second FMT at which sFMT is still preferred. Value of information analysis estimates the expected value of perfect information to be low at $1.89 per person, quantified with net monetary benefit.<br><br>CONCLUSIONS: An sFMT strategy strongly dominates standard therapy, with lower cost and higher QALY. Sensitivity analysis demonstrates benefit even if FMT cure rates are lower than expected and when multiple FMTs are required. FMT material in 2020 was priced at $1695 per treatment but remains cost-effective at a much higher cost.}, }
@article {pmid33678185, year = {2021}, author = {Jing, Y and Yu, Y and Bai, F and Wang, L and Yang, D and Zhang, C and Qin, C and Yang, M and Zhang, D and Zhu, Y and Li, J and Chen, Z}, title = {Effect of fecal microbiota transplantation on neurological restoration in a spinal cord injury mouse model: involvement of brain-gut axis.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {59}, pmid = {33678185}, issn = {2049-2618}, mesh = {Animals ; Brain/*physiology ; Fatty Acids, Volatile/metabolism ; *Fecal Microbiota Transplantation ; Feces/chemistry ; Female ; Gastrointestinal Microbiome/*physiology ; Interleukin-1beta/metabolism ; Intestines/microbiology/physiology ; Locomotion ; Mice ; Mice, Inbred C57BL ; NF-kappa B/metabolism ; Neuroprotection/*physiology ; Signal Transduction ; Spinal Cord Injuries/pathology/*therapy ; }, abstract = {BACKGROUND: Spinal cord injury (SCI) patients display disruption of gut microbiome, and gut dysbiosis exacerbate neurological impairment in SCI models. Cumulative data support an important role of gut microbiome in SCI. Here, we investigated the hypothesis that fecal microbiota transplantation (FMT) from healthy uninjured mice into SCI mice may exert a neuroprotective effect.<br><br>RESULTS: FMT facilitated functional recovery, promoted neuronal axonal regeneration, improved animal weight gain and metabolic profiling, and enhanced intestinal barrier integrity and GI motility in SCI mice. High-throughput sequencing revealed that levels of phylum Firmicutes, family Christensenellaceae, and genus Butyricimonas were reduced in fecal samples of SCI mice, and FMT remarkably reshaped gut microbiome. Also, FMT-treated SCI mice showed increased amount of fecal short-chain fatty acids (SCFAs), which correlated with alteration of intestinal permeability and locomotor recovery. Furthermore, FMT downregulated IL-1β/NF-κB signaling in spinal cord and NF-κB signaling in gut following SCI.<br><br>CONCLUSION: Our study demonstrates that reprogramming of gut microbiota by FMT improves locomotor and GI functions in SCI mice, possibly through the anti-inflammatory functions of SCFAs. Video Abstract.}, }
@article {pmid33677218, year = {2021}, author = {Rao, J and Qiao, Y and Xie, R and Lin, L and Jiang, J and Wang, C and Li, G}, title = {Fecal microbiota transplantation ameliorates stress-induced depression-like behaviors associated with the inhibition of glial and NLRP3 inflammasome in rat brain.}, journal = {Journal of psychiatric research}, volume = {137}, number = {}, pages = {147-157}, doi = {10.1016/j.jpsychires.2021.02.057}, pmid = {33677218}, issn = {1879-1379}, mesh = {Animals ; Brain/metabolism ; Depression/etiology/therapy ; Fecal Microbiota Transplantation ; *Inflammasomes/metabolism ; *NLR Family, Pyrin Domain-Containing 3 Protein ; Neuroglia ; Rats ; Stress, Psychological/therapy ; }, abstract = {BACKGROUND: Evidence from previous studies has demonstrated that the gut-microbiota-brain axis is vital in regulating of behavior and neuroinflammation in the central nervous system. Considering the putative connection among gut microbiota, neural function, and behavior, the present study investigated the potential signaling of gut microbiota to modulate depression-like behaviors and neuroinflammation.<br><br>METHODS: Rats showing depression-like behaviors induced by chronic unpredictable mild stress received fecal microbiota treatment or vehicle for 14 days, and alterations in behavior and neuroinflammation were assessed. ELISA, immunofluorescence staining and Western blot were used to analysis the activation of glial cells and NLRP3 inflammasome.<br><br>RESULTS: Treatment with fecal microbiota transplantation ameliorated depression-like behaviors. 5-Hydroxytryptamine decreased in the chronic unpredictable mild stress rat model but significantly increased after fecal microbiota transplantation. The treatment with fecal microbiota transplantation decreased the production of IL-1β and TNF-α. Moreover, fecal microbiota transplantation administration suppressed the activation of Iba1 positive microglia cells and GFAP positive astrocytes cells and reduced the expression of NLRP3, ASC, Caspase-1, and IL-1β pathway in the prefrontal cortex and hippocampus.<br><br>CONCLUSIONS: Fecal microbiota transplantation can improve depression-like behaviors induced by chronic unpredictable mild stress. The anti-depression effects of fecal microbiota transplantation were associated with the suppressed activation of glial cells and NLRP3 inflammasome in the brain.}, }
@article {pmid33670255, year = {2021}, author = {Verdier, C and Denis, S and Gasc, C and Boucinha, L and Uriot, O and Delmas, D and Dore, J and Le Camus, C and Schwintner, C and Blanquet-Diot, S}, title = {An Oral FMT Capsule as Efficient as an Enema for Microbiota Reconstruction Following Disruption by Antibiotics, as Assessed in an In Vitro Human Gut Model.}, journal = {Microorganisms}, volume = {9}, number = {2}, pages = {}, pmid = {33670255}, issn = {2076-2607}, abstract = {Fecal microbiota transplantation (FMT) is an innovative therapy already used in humans to treat Clostridioides difficile infections associated with massive use of antibiotics. Clinical studies are obviously the gold standard to evaluate FMT efficiency but remain limited by regulatory, ethics, and cost constraints. In the present study, an in vitro model of the human colon reproducing medically relevant perturbation of the colonic ecosystem by antibiotherapy was used to compare the efficiency of traditional FMT enema formulations and a new oral capsule in restoring gut microbiota composition and activity. Loss of microbial diversity, shift in bacterial populations, and sharp decrease in fermentation activities induced in vivo by antibiotherapy were efficiently reproduced in the in vitro model, while capturing inter-individual variability of gut microbiome. Oral capsule was as efficient as enema to decrease the number of disturbed days and bacterial load had no effect on enema performance. This study shows the relevance of human colon models as an alternative approach to in vivo assays during preclinical studies for evaluating FMT efficiency. The potential of this in vitro approach could be extended to FMT testing in the management of many digestive or extra-intestinal pathologies where gut microbial dysbiosis has been evidenced such as inflammatory bowel diseases, obesity or cancers.}, }
@article {pmid33669988, year = {2021}, author = {Shabbir, U and Arshad, MS and Sameen, A and Oh, DH}, title = {Crosstalk between Gut and Brain in Alzheimer's Disease: The Role of Gut Microbiota Modulation Strategies.}, journal = {Nutrients}, volume = {13}, number = {2}, pages = {}, pmid = {33669988}, issn = {2072-6643}, support = {Grant No. 22A20153713433//Brain Korea (BK) 21 Plus Project/ ; }, mesh = {Alzheimer Disease/*microbiology ; Animals ; Blood-Brain Barrier/microbiology ; Brain/*microbiology ; Diet Therapy ; Dysbiosis/metabolism/psychology/*therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Intestinal Mucosa/*metabolism ; Permeability ; Probiotics/therapeutic use ; }, abstract = {The gut microbiota (GM) represents a diverse and dynamic population of microorganisms and about 100 trillion symbiotic microbial cells that dwell in the gastrointestinal tract. Studies suggest that the GM can influence the health of the host, and several factors can modify the GM composition, such as diet, drug intake, lifestyle, and geographical locations. Gut dysbiosis can affect brain immune homeostasis through the microbiota-gut-brain axis and can play a key role in the pathogenesis of neurodegenerative diseases, including dementia and Alzheimer's disease (AD). The relationship between gut dysbiosis and AD is still elusive, but emerging evidence suggests that it can enhance the secretion of lipopolysaccharides and amyloids that may disturb intestinal permeability and the blood-brain barrier. In addition, it can promote the hallmarks of AD, such as oxidative stress, neuroinflammation, amyloid-beta formation, insulin resistance, and ultimately the causation of neural death. Poor dietary habits and aging, along with inflammatory responses due to dysbiosis, may contribute to the pathogenesis of AD. Thus, GM modulation through diet, probiotics, or fecal microbiota transplantation could represent potential therapeutics in AD. In this review, we discuss the role of GM dysbiosis in AD and potential therapeutic strategies to modulate GM in AD.}, }
@article {pmid33669557, year = {2021}, author = {Giampaolino, P and Foreste, V and Di Filippo, C and Gallo, A and Mercorio, A and Serafino, P and Improda, FP and Verrazzo, P and Zara, G and Buonfantino, C and Borgo, M and Riemma, G and Angelis, C and Zizolfi, B and Bifulco, G and Della Corte, L}, title = {Microbiome and PCOS: State-of-Art and Future Aspects.}, journal = {International journal of molecular sciences}, volume = {22}, number = {4}, pages = {}, pmid = {33669557}, issn = {1422-0067}, mesh = {Animals ; Diet ; Female ; *Gastrointestinal Microbiome ; Genitalia, Female/microbiology ; Hormones/metabolism ; Humans ; Insulin Resistance ; Polycystic Ovary Syndrome/*microbiology/therapy ; }, abstract = {Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disease. The hypothesis that alterations in the microbiome are involved in the genesis of PCOS has been postulated. Aim of this review is to summarize the available literature data about the relationship between microbiome and PCOS. A search on PubMed and Medline databases was performed from inception to November 20Most of evidence has focused on the connection of intestinal bacteria with sex hormones and insulin-resistance: while in the first case, a relationship with hyperandrogenism has been described, although it is still unclear, in the second one, chronic low-grade inflammation by activating the immune system, with increased production of proinflammatory cytokines which interfere with insulin receptor function, causing IR (Insulin Resistance)/hyperinsulinemia has been described, as well as the role of gastrointestinal hormones like Ghrelin and peptide YY (PYY), bile acids, interleukin-22 and Bacteroides vulgatus have been highlighted. The lower genital tract microbiome would be affected by changes in PCOS patients too. The therapeutic opportunities include probiotic, prebiotics and synbiotics, as well as fecal microbiota transplantation and the use of IL-22, to date only in animal models, as a possible future drug. Current evidence has shown the involvement of the gut microbiome in PCOS, seen how humanized mice receiving a fecal transplant from women with PCOS develop ovarian dysfunction, immune changes and insulin resistance and how it is capable of disrupting the secondary bile acid biosynthesis. A future therapeutic approach for PCOS may involve the human administration of IL-22 and bile acid glycodeoxycholic acid.}, }
@article {pmid33668518, year = {2021}, author = {Ciernikova, S and Mego, M and Chovanec, M}, title = {Exploring the Potential Role of the Gut Microbiome in Chemotherapy-Induced Neurocognitive Disorders and Cardiovascular Toxicity.}, journal = {Cancers}, volume = {13}, number = {4}, pages = {}, pmid = {33668518}, issn = {2072-6694}, support = {APVV-19-0411 and APVV-15-0086//Agentúra na Podporu Výskumu a Vývoja/ ; 2/0052/18 and 1/0327/19//Vedecká Grantová Agentúra MŠVVaŠ SR a SAV/ ; }, abstract = {Chemotherapy, targeting not only malignant but also healthy cells, causes many undesirable side effects in cancer patients. Due to this fact, long-term cancer survivors often suffer from late effects, including cognitive impairment and cardiovascular toxicity. Chemotherapy damages the intestinal mucosa and heavily disrupts the gut ecosystem, leading to gastrointestinal toxicity. Animal models and clinical studies have revealed the associations between intestinal dysbiosis and depression, anxiety, pain, impaired cognitive functions, and cardiovascular diseases. Recently, a possible link between chemotherapy-induced gut microbiota disruption and late effects in cancer survivors has been proposed. In this review, we summarize the current understanding of preclinical and clinical findings regarding the emerging role of the microbiome and the microbiota-gut-brain axis in chemotherapy-related late effects affecting the central nervous system (CNS) and heart functions. Importantly, we provide an overview of clinical trials evaluating the relationship between the gut microbiome and cancer survivorship. Moreover, the beneficial effects of probiotics in experimental models and non-cancer patients with neurocognitive disorders and cardiovascular diseases as well as several studies on microbiota modulations via probiotics or fecal microbiota transplantation in cancer patients are discussed.}, }
@article {pmid33667294, year = {2021}, author = {Ranallo, RT and McDonald, LC and Halpin, AL and Hiltke, T and Young, VB}, title = {The State of Microbiome Science at the Intersection of Infectious Diseases and Antimicrobial Resistance.}, journal = {The Journal of infectious diseases}, volume = {223}, number = {Supplement_3}, pages = {S187-S193}, pmid = {33667294}, issn = {1537-6613}, abstract = {Along with the rise in modern chronic diseases, ranging from diabetes to asthma, there are challenges posed by increasing antibiotic resistance, which results in difficult-to-treat infections, as well as sepsis. An emerging and unifying theme in the pathogenesis of these diverse public health threats is changes in the microbial communities that inhabit multiple body sites. Although there is great promise in exploring the role of these microbial communities in chronic disease pathogenesis, the shorter timeframe of most infectious disease pathogenesis may allow early translation of our basic scientific understanding of microbial ecology and host-microbiota-pathogen interactions. Likely translation avenues include development of preventive strategies, diagnostics, and therapeutics. For example, as basic research related to microbial pathogenesis continues to progress, Clostridioides difficile infection is already being addressed clinically through at least 2 of these 3 avenues: targeted antibiotic stewardship and treatment of recurrent disease through fecal microbiota transplantation.}, }
@article {pmid33666892, year = {2021}, author = {El-Salhy, M and Patcharatrakul, T and Gonlachanvit, S}, title = {The role of diet in the pathophysiology and management of irritable bowel syndrome.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {40}, number = {2}, pages = {111-119}, pmid = {33666892}, issn = {0975-0711}, support = {40415//Helse Fonna/ ; }, abstract = {Irritable bowel syndrome (IBS) is a chronic gastrointestinal (GI) disorder that reportedly affects 5% to 20% of the world population. The etiology of IBS is not completely understood, but diet appears to play an important role in its pathophysiology. Asian diets differ considerably from those in Western countries, which might explain differences in the prevalence, sex, and clinical presentation seen between patients with IBS in Asian and Western countries. Dietary regimes such as a low-fermentable oligo-, di-, monosaccharides, and polyols (FODMAP) diet and the modified National Institute for Health and Care Excellence (NICE) diet improve both symptoms and the quality of life in a considerable proportion of IBS patients. It has been speculated that diet is a prebiotic for the intestinal microbiota and favors the growth of certain bacteria. These bacteria ferment the dietary components, and the products of fermentation act upon intestinal stem cells to influence their differentiation into enteroendocrine cells. The resulting low density of enteroendocrine cells accompanied by low levels of certain hormones gives rise to intestinal dysmotility, visceral hypersensitivity, and abnormal secretion. This hypothesis is supported by the finding that changing to a low-FODMAP diet restores the density of GI cells to the levels in healthy subjects. These changes in gut endocrine cells caused by low-FODMAP diet are also accompanied by improvements in symptoms and the quality of life.}, }
@article {pmid33663713, year = {2021}, author = {Kopper, JJ and Alexander, TL and Kogan, CJ and Berreta, AR and Burbick, CR}, title = {In Vitro Evaluation of the Effect of Storage at -20°C and Proximal Gastrointestinal Conditions on Viability of Equine Fecal Microbiota Transplant.}, journal = {Journal of equine veterinary science}, volume = {98}, number = {}, pages = {103360}, doi = {10.1016/j.jevs.2020.103360}, pmid = {33663713}, issn = {0737-0806}, mesh = {Animals ; Dysbiosis/veterinary ; Fecal Microbiota Transplantation/veterinary ; Feces ; *Gastrointestinal Microbiome ; *Horse Diseases ; Horses ; *Microbiota ; }, abstract = {Fecal microbiota transplant (FMT), a technique used to restore normal intestinal microbial communities, has been successful in treating humans with Clostridioides difficile colitis. Subsequently, FMT is being used in veterinary patients with suspected intestinal dysbiosis. Unfortunately, little data are available regarding best practices for FMT in horses. The objective of this study was to evaluate the effects of storing manure prepared for equine FMT (MP-FMT) at -20°C for up to 4 weeks and passage through a simulated proximal gastrointestinal (GI) tract on the viability of MP-FMT. The results of this study indicate that storage at -20°C for greater than 1 week and exposure to conditions consistent with the proximal GI tract significantly decreased viability of the microbial population, with gram-negative enteric bacteria most significantly impacted. This preliminary evaluation indicates that further work is necessary to determine best practices to preserve the viability MP-FMT in horses.}, }
@article {pmid33662679, year = {2021}, author = {Xu, JY and Liu, MT and Tao, T and Zhu, X and Fei, FQ}, title = {The role of gut microbiota in tumorigenesis and treatment.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {138}, number = {}, pages = {111444}, doi = {10.1016/j.biopha.2021.111444}, pmid = {33662679}, issn = {1950-6007}, mesh = {Animals ; Carcinogenesis/drug effects/*metabolism ; Cell Transformation, Neoplastic/drug effects/metabolism ; Dysbiosis/*metabolism/*therapy ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/drug effects/*physiology ; Gastrointestinal Neoplasms/*metabolism/*therapy ; Humans ; Probiotics/administration &amp; dosage ; Treatment Outcome ; }, abstract = {A large number of microbial communities exist in normal human intestinal tracts, which maintain a relatively stable dynamic balance under certain conditions. Gut microbiota are closely connected with human health and the occurrence of tumors. The colonization of certain intestinal bacteria on specific sites, gut microbiota disturbance and intestinal immune disorders can induce the occurrence of tumors. Meanwhile, gut microbiota can also play a role in tumor therapy by participating in immune regulation, influencing the efficacy of anti-tumor drugs, targeted therapy of engineered probiotics and fecal microbiota transplantation. This article reviews the role of gut microbiota in the occurrence, development, diagnosis and treatment of tumors. A better understanding of how gut microbiota affect tumors will help us find more therapies to treat the disease.}, }
@article {pmid33660961, year = {2021}, author = {Mikolašević, I and Hauser, G and Abram, M and Filipec Kanižaj, T and Radić, M and Krznarić Zrnić, I}, title = {Fecal microbiota transplantation - where are we?.}, journal = {Croatian medical journal}, volume = {62}, number = {1}, pages = {52-58}, pmid = {33660961}, issn = {1332-8166}, mesh = {*Fecal Microbiota Transplantation ; Feces ; Humans ; Treatment Outcome ; }, }
@article {pmid33659945, year = {2020}, author = {Khurana, S and Kahl, A and Yu, K and DuPont, AW}, title = {Recent advances in the treatment of Clostridioides difficile infection: the ever-changing guidelines.}, journal = {Faculty reviews}, volume = {9}, number = {}, pages = {13}, pmid = {33659945}, issn = {2732-432X}, abstract = {Clostridioides difficile infection (CDI), formerly known as Clostridium difficile, continues to be the most common healthcare-associated infection worldwide. With the shifting epidemiology towards higher a incidence of community-acquired CDI and the continued burden on the healthcare system posed by high rates of CDI recurrence, there has been an impetus to advance the diagnostic testing and treatment strategies. Recent advancements over the past decade have led to rapidly changing guidelines issued by the Infectious Diseases Society of America and European Society of Clinical Microbiology and Infectious Diseases. With our comprehensive review, we aim to summarize the latest advances in diagnosing and treating CDI and thus attempt to help readers guide best practices for patient care. This article also focusses on cost-effectiveness of various therapies currently available on the market and provides an analysis of the current evidence on a relatively new monoclonal antibody therapy, Bezlotoxumab, to treat recurrent CDI.}, }
@article {pmid33659796, year = {2020}, author = {Тикунов, АЮ and Морозов, ВВ and Швалов, АН and Бардашева, АВ and Шрайнер, ЕВ and Максимова, ОА and Волошина, ИО and Морозова, ВВ and Власов, ВВ and Тикунова, НВ}, title = {[Fecal microbiome change in patients with ulcerative colitis after fecal microbiota transplantation].}, journal = {Vavilovskii zhurnal genetiki i selektsii}, volume = {24}, number = {2}, pages = {168-175}, doi = {10.18699/VJ20.610}, pmid = {33659796}, issn = {2500-0462}, abstract = {Intestinal human microbiota is a dynamic system that is under the pressures of its host organism and external factors. Microbiota disruption caused by these factors can lead to severe diseases including inflammatory and oncological diseases of the gastrointestinal tract. One of the possible approaches in managing the intestinal microbiota is fecal microbiota transplantation (FT) - transfer of the microbiota from the stool of a healthy donor to the intestinal tract of a recipient patient. Currently, this procedure is recognized as an efficacious method to normalize the intestinal microbiota mainly in inflammatory diseases of the gastrointestinal tract. In Russia, pilot studies of the effectiveness of FT in patients with ulcerative colitis have been conducted for several years, and these studies were started in Novosibirsk. The aim of this study was to assess the change of intestinal microbiome in 20 patients with ulcerative colitis after a single FT procedure. The main method is a comparative analysis of 16S ribosomal RNA sequence libraries constructed using fecal samples obtained from patients with ulcerative colitis before and after FT and sequenced on the Illumina MiSeq platform. The obtained results showed that FT led to an increase in average biodiversity in samples after FT compared to samples before FT; however, the difference was not significant. In the samples studied, the proportion of Firmicutes sequences, the major gastrointestinal microbiota of healthy people, was decreased (~32 % vs. >70 %), while the proportion of Proteobacteria sequences was increased (>9 % vs. <5 %). In some samples collected before FT, sequences of pathogenic Firmicutes and Proteobacteria were detected, including Acinetobacter spp., Enterococcus spp., Klebsiella pneumoniae, Proteus mirabilis, Staphylococcus aureus, Stenotrophomonas maltophylia, Streptococcus spp. In most cases, the proportion of such sequences after FT substantially decreased in appropriate samples. The exception was the Clostridium difficile sequences, which accounted for <0.5 % of the sequences in samples from almost half of the patients and after FT, the share of such C. difficile sequences was significantly reduced only in samples from three patients. It should be noted that the proportion of Lactobacillus spp. increased ten-fold and their species composition significantly expanded. According to the obtained results, a preliminary conclusion can be made that even a single FT procedure can lead to an increase in the biodiversity of the gastrointestinal microbiota in patients and to the optimization of the taxonomic composition of the microbiota.}, }
@article {pmid33658399, year = {2021}, author = {Huang, J and Shan, W and Li, F and Wang, Z and Cheng, J and Lu, F and Guo, E and Beejadhursing, R and Xiao, R and Liu, C and Yang, B and Li, X and Fu, Y and Xi, L and Wang, S and Ma, D and Chen, G and Sun, C}, title = {Fecal microbiota transplantation mitigates vaginal atrophy in ovariectomized mice.}, journal = {Aging}, volume = {13}, number = {5}, pages = {7589-7607}, pmid = {33658399}, issn = {1945-4589}, mesh = {Animals ; Atrophy ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/genetics/physiology ; Mice ; Mice, Inbred C57BL ; Ovariectomy/*adverse effects ; RNA, Ribosomal, 16S/genetics ; Vagina/*pathology ; }, abstract = {Vulvovaginal atrophy (VVA) is a common menopause-related symptom affecting more than 50% of midlife and older women and cancer patients whose ovarian function are lost or damaged. Regardless of estrogen deficiency, whether other factors such as the gut microbiota play role in VVA have not been thoroughly investigated. To this end, we performed ovariectomy on 12-weeks' old mice and follow-up at 4 weeks after ovariectomy, and observed atrophied vagina and an altered gut microbiota in ovariectomized mice.. We further performed fecal microbiota transplantation with feces from another cohort of ovary-intact fecund female mice to the ovariectomized ones, and found that the vaginal epithelial atrophy was significantly alleviated as well as the gut microbiota was pointedly changed. All these results suggest that ovarian activity has some influence on the gut microbiota, and the latter from the ovary-intact female mice can somehow make the vagina of mice deficient in ovarian function healthier maybe by up-expressing ESR1 in vaginal cells and enhancing regeneration in vagina. This kind of association between gut microbiota and vaginal health need further exploration such that it may provide an alternative treatment by modulating gut microbiota in patients suffering from VVA but may be reluctant to hormone therapy.}, }
@article {pmid33654104, year = {2021}, author = {Liao, C and Taylor, BP and Ceccarani, C and Fontana, E and Amoretti, LA and Wright, RJ and Gomes, ALC and Peled, JU and Taur, Y and Perales, MA and van den Brink, MRM and Littmann, E and Pamer, EG and Schluter, J and Xavier, JB}, title = {Compilation of longitudinal microbiota data and hospitalome from hematopoietic cell transplantation patients.}, journal = {Scientific data}, volume = {8}, number = {1}, pages = {71}, pmid = {33654104}, issn = {2052-4463}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; R01 AI137269/AI/NIAID NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; U54 CA209975/CA/NCI NIH HHS/United States ; }, mesh = {Feces/microbiology ; *Gastrointestinal Microbiome ; *Hematopoietic Stem Cell Transplantation ; *Hospitalization ; Humans ; RNA, Ribosomal, 16S/genetics ; United States ; }, abstract = {The impact of the gut microbiota in human health is affected by several factors including its composition, drug administrations, therapeutic interventions and underlying diseases. Unfortunately, many human microbiota datasets available publicly were collected to study the impact of single variables, and typically consist of outpatients in cross-sectional studies, have small sample numbers and/or lack metadata to account for confounders. These limitations can complicate reusing the data for questions outside their original focus. Here, we provide comprehensive longitudinal patient dataset that overcomes those limitations: a collection of fecal microbiota compositions (>10,000 microbiota samples from >1,000 patients) and a rich description of the "hospitalome" experienced by the hosts, i.e., their drug exposures and other metadata from patients with cancer, hospitalized to receive allogeneic hematopoietic cell transplantation (allo-HCT) at a large cancer center in the United States. We present five examples of how to apply these data to address clinical and scientific questions on host-associated microbial communities.}, }
@article {pmid33654015, year = {2021}, author = {Dalal, RS and Allegretti, JR}, title = {Diagnosis and management of Clostridioides difficile infection in patients with inflammatory bowel disease.}, journal = {Current opinion in gastroenterology}, volume = {37}, number = {4}, pages = {336-343}, doi = {10.1097/MOG.0000000000000739}, pmid = {33654015}, issn = {1531-7056}, support = {T32 DK007533/DK/NIDDK NIH HHS/United States ; }, abstract = {PURPOSE OF REVIEW: Clostridioides difficile infection (CDI) may complicate the course of ulcerative colitis and Crohn's disease. The clinical presentation of CDI in this population is often atypical, and patients may experience exacerbations of their underlying inflammatory bowel disease (IBD) secondary to C. difficile. In this review, we aim to review the risk factors, diagnosis, and management of CDI in the context of IBD.<br><br>RECENT FINDINGS: Patients with colonic involvement of their IBD are at higher risk for CDI and colonization may be more common than in the general population. Therefore, CDI is confirmed using a two-step approach to stool testing. Oral vancomycin or fidaxomicin are the preferred agents for nonfulminant disease, and oral metronidazole is no longer recommended as first-line therapy. For all patients with CDI recurrence, fecal microbiota transplant (FMT) should be considered, as this has been shown to be safe and effective. Among those who have worsening of their underlying IBD, retrospective research suggest that outcomes are improved for those who undergo escalation of immunosuppression with appropriate antimicrobial treatment of C. difficile, however prospective data are needed.<br><br>SUMMARY: CDI may complicate the course of IBD, however the presentation may not be typical. Therefore, all patients with worsening gastrointestinal symptoms should be evaluated for both CDI and IBD exacerbation. Providers should consider FMT for all patients with recurrent CDI as well as escalation of immunosuppression for patients who fail to improve with appropriate antimicrobial therapy.}, }
@article {pmid33653967, year = {2021}, author = {Grajeda-Iglesias, C and Durand, S and Daillère, R and Iribarren, K and Lemaitre, F and Derosa, L and Aprahamian, F and Bossut, N and Nirmalathasan, N and Madeo, F and Zitvogel, L and Kroemer, G}, title = {Oral administration of Akkermansia muciniphila elevates systemic antiaging and anticancer metabolites.}, journal = {Aging}, volume = {13}, number = {5}, pages = {6375-6405}, pmid = {33653967}, issn = {1945-4589}, mesh = {Administration, Oral ; Akkermansia ; Animals ; Fatty Acids, Volatile/metabolism ; Gastrointestinal Microbiome ; Gastrointestinal Tract/metabolism ; Hydroxybutyrates/metabolism ; Liver/metabolism ; Metabolome ; Metabolomics ; Mice, Inbred C57BL ; Pasteurization ; Polyamines/metabolism ; Probiotics/*pharmacology ; Spermidine/metabolism ; }, abstract = {The presence of Akkermansia muciniphila (Akk) in the human gut is associated with good health, leanness and fitness. Mouse experimentation has demonstrated positive effects for Akk, which counteracts aging, mediates antiobesity and antidiabetic effects, dampens inflammation and improves anticancer immunosurveillance. Clinical trials have confirmed antidiabetic effects for Akk. Here, we investigated the time-dependent effects of oral administration of Akk (which was live or pasteurized) and other bacteria to mice on the metabolome of the ileum, colon, liver and blood plasma. Metabolomics was performed by a combination of chromatographic and mass spectrometric methods, yielding a total of 1.637.227 measurements. Akk had major effects on metabolism, causing an increase in spermidine and other polyamines in the gut and in the liver. Pasteurized Akk (Akk-past) was more efficient than live Akk in elevating the intestinal concentrations of polyamines, short-chain fatty acids, 2-hydroxybutyrate, as well multiple bile acids, which also increased in the circulation. All these metabolites have previously been associated with human health, providing a biochemical basis for the beneficial effects of Akk.}, }
@article {pmid33652903, year = {2021}, author = {Khor, B and Snow, M and Herrman, E and Ray, N and Mansukhani, K and Patel, KA and Said-Al-Naief, N and Maier, T and Machida, CA}, title = {Interconnections Between the Oral and Gut Microbiomes: Reversal of Microbial Dysbiosis and the Balance Between Systemic Health and Disease.}, journal = {Microorganisms}, volume = {9}, number = {3}, pages = {}, pmid = {33652903}, issn = {2076-2607}, abstract = {The human microbiota represents a complex array of microbial species that influence the balance between the health and pathology of their surrounding environment. These microorganisms impart important biological benefits to their host, such as immune regulation and resistance to pathogen colonization. Dysbiosis of microbial communities in the gut and mouth precede many oral and systemic diseases such as cancer, autoimmune-related conditions, and inflammatory states, and can involve the breakdown of innate barriers, immune dysregulation, pro-inflammatory signaling, and molecular mimicry. Emerging evidence suggests that periodontitis-associated pathogens can translocate to distant sites to elicit severe local and systemic pathologies, which necessitates research into future therapies. Fecal microbiota transplantation, probiotics, prebiotics, and synbiotics represent current modes of treatment to reverse microbial dysbiosis through the introduction of health-related bacterial species and substrates. Furthermore, the emerging field of precision medicine has been shown to be an effective method in modulating host immune response through targeting molecular biomarkers and inflammatory mediators. Although connections between the human microbiome, immune system, and systemic disease are becoming more apparent, the complex interplay and future innovations in treatment modalities will become elucidated through continued research and cross-disciplinary collaboration.}, }
@article {pmid33652261, year = {2021}, author = {Yang, S and Hu, T and Liu, H and Lv, YL and Zhang, W and Li, H and Xuan, L and Gong, LL and Liu, LH}, title = {Akebia saponin D ameliorates metabolic syndrome (MetS) via remodeling gut microbiota and attenuating intestinal barrier injury.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {138}, number = {}, pages = {111441}, doi = {10.1016/j.biopha.2021.111441}, pmid = {33652261}, issn = {1950-6007}, mesh = {Animals ; Cell Line ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*drug effects/physiology ; Humans ; Intestinal Mucosa/*drug effects/metabolism/pathology ; Male ; Metabolic Syndrome/*drug therapy/metabolism/pathology ; Mice ; Mice, Inbred C57BL ; Saponins/pharmacology/*therapeutic use ; }, abstract = {Metabolic syndrome (MetS) is a complex, multifactorial disease which lead to an increased risk of cardiovascular disease, type 2 diabetes, and stroke. However, selective, and potent drugs for the treatment of MetS are still lacking. Previous studies have found that Akebia saponin D (ASD) has beneficial effects on metabolic diseases such as obesity, atherosclerosis, and non-alcoholic fatty liver disease (NAFLD). Therefore, our study was designed to determine the effect and mechanism of action of ASD against MetS in a high-fat diet (HFD) induced mouse model. ASD significantly decreased plasma lipid and insulin resistance in these mice, and a targeted approach using metabolomic analyses of plasma and feces indicated that glucose and lipids in these mice crossed the damaged intestinal barrier into circulation. Furthermore, ASD was able to increase lipid excretion and inhibit intestinal epithelial lipid absorption. Results for gut microbiota composition showed that ASD significantly reduced HFD-associated Alistipes, Prevotella, and enhanced the proportions of Butyricimonas, Ruminococcus, and Bifidobacterium. After 14 weeks of ASD/fecal microbiota transplantation (FMT) interventions the developed gut barrier dysfunction was restored. Additionally, RNA-seq revealed that ASD reduced the lipid-induced tight junction (TJ) damage in intestinal epithelial cells via down-regulation of the PPAR-γ-FABP4 pathway in vitro and that use of the PPAR-γ inhibitor (T0070907) was able to partially block the effects of ASD, indicating that the PPAR-γ/FABP4 pathway is a critical mediator involved in the improvement of MetS. Our results demonstrated that ASD not only modifies the gut microbiome but also ameliorates the HFD-induced gut barrier disruption via down-regulation of the PPAR-γ-FABP4 pathway. These findings suggest a promising, and novel therapeutic strategy for gut protection against MetS.}, }
@article {pmid33651137, year = {2021}, author = {Ghorbani, Y and Schwenger, KJP and Allard, JP}, title = {Manipulation of intestinal microbiome as potential treatment for insulin resistance and type 2 diabetes.}, journal = {European journal of nutrition}, volume = {60}, number = {5}, pages = {2361-2379}, pmid = {33651137}, issn = {1436-6215}, mesh = {*Diabetes Mellitus, Type 2/therapy ; *Gastrointestinal Microbiome ; Humans ; *Insulin Resistance ; Prebiotics ; *Probiotics ; *Synbiotics ; }, abstract = {PURPOSE: Increasing evidence suggests that the intestinal microbiome (IM) and bacterial metabolites may influence glucose homeostasis, energy expenditure and the intestinal barrier integrity and lead to the presence of systemic low-grade inflammation, all of which can contribute to insulin resistance (IR) and type 2 diabetes (T2D). The purpose of this review is to explore the role of the IM and bacterial metabolites in the pathogenesis and treatment of these conditions.<br><br>RESULTS: This review summarizes research focused on how to modulate the IM through diet, prebiotics, probiotics, synbiotics and fecal microbiota transplant in order to treat IR and T2D.<br><br>CONCLUSION: There is an abundance of evidence suggesting a role for IM in the pathogenesis of IR and T2D based on reviewed studies using various methods to modulate IM and metabolites. However, the results are inconsistent. Future research should further assess this relationship.}, }
@article {pmid33643302, year = {2020}, author = {Liu, Y and Li, Z and Wu, Y and Jing, X and Li, L and Fang, X}, title = {Intestinal Bacteria Encapsulated by Biomaterials Enhance Immunotherapy.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {620170}, pmid = {33643302}, issn = {1664-3224}, mesh = {Administration, Oral ; Animals ; Antigen-Presenting Cells/immunology ; B-Lymphocytes/immunology ; Biocompatible Materials/*administration &amp; dosage ; *Cell Encapsulation ; DNA, Bacterial/administration &amp; dosage ; Drug Carriers/administration &amp; dosage ; *Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome/immunology/physiology ; Humans ; Immunotherapy/*methods ; Injections, Intravenous ; Macrophages/immunology ; Mice ; Mice, Inbred C57BL ; Probiotics/administration &amp; dosage ; T-Lymphocyte Subsets/immunology ; }, abstract = {The human intestine contains thousands of bacterial species essential for optimal health. Aside from their pathogenic effects, these bacteria have been associated with the efficacy of various treatments of diseases. Due to their impact on many human diseases, intestinal bacteria are receiving increasing research attention, and recent studies on intestinal bacteria and their effects on treatments has yielded valuable results. Particularly, intestinal bacteria can affect responses to numerous forms of immunotherapy, especially cancer therapy. With the development of precision medicine, understanding the factors that influence intestinal bacteria and how they can be regulated to enhance immunotherapy effects will improve the application prospects of intestinal bacteria therapy. Further, biomaterials employed for the convenient and efficient delivery of intestinal bacteria to the body have also become a research hotspot. In this review, we discuss the recent findings on the regulatory role of intestinal bacteria in immunotherapy, focusing on immune cells they regulate. We also summarize biomaterials used for their delivery.}, }
@article {pmid33639935, year = {2021}, author = {Al-Bakri, AG and Akour, AA and Al-Delaimy, WK}, title = {Knowledge, attitudes, ethical and social perspectives towards fecal microbiota transplantation (FMT) among Jordanian healthcare providers.}, journal = {BMC medical ethics}, volume = {22}, number = {1}, pages = {19}, pmid = {33639935}, issn = {1472-6939}, support = {5R25TW010026-02/TW/FIC NIH HHS/United States ; }, mesh = {Cross-Sectional Studies ; *Fecal Microbiota Transplantation ; Feces ; Health Knowledge, Attitudes, Practice ; Humans ; *Microbiota ; }, abstract = {BACKGROUND: Fecal microbiota transplant (FMT) is a treatment modality that involves the introduction of stool from a healthy pre-screened donor into the gastrointestinal tract of a patient. It exerts its therapeutic effects by remodeling the gut microbiota and treating microbial dysbiosis-imbalance. FMT is not regulated in Jordan, and regulatory effort for FMT therapy in Jordan, an Islamic conservative country, might be faced with unique cultural, social, religious, and ethical challenges. We aimed to assess knowledge, attitudes, and perceptions of ethical and social issues of FMT use among Jordanian healthcare professionals.<br><br>METHODS: An observational, cross-sectional study design was used to assess knowledge, attitudes, and perceptions of ethical and social issues of FMT among 300 Jordanian healthcare professionals.<br><br>RESULTS: A large proportion (39 %) thought that the safety and efficacy of this technique are limited and 29.3 % thought there is no evidence to support its use. Almost all (95 %) responded that they would only perform it in certain cases, if ethically justified, and 48.3 % would use it due to treatment failure of other approaches. When reporting about reasons for not using it, 40 % reported that they would not perform it due to concerns about medical litigation, fear of infections (38 %), and lack of knowledge of long safety and efficacy (31.3 %). Interestingly, all practitioners said they would perform this procedure through the lower rather than upper gastrointestinal tract modality and the majority will protect the patient's confidentiality via double-blinding (43.3 %). For a subset of participants (n = 100), the cultural constraints that might affect the choice of performing FMT were mainly due to donor's religion, followed by dietary intake, and alcohol consumption.<br><br>CONCLUSIONS: Our healthcare practitioners are generally reluctant to use the FMT modality due to religious and ethical reasons but would consider it if there was a failure of other treatment and after taking into consideration many legislative, social, ethical and practice-based challenges including safety, efficacy and absence of guidelines.}, }
@article {pmid33639698, year = {2021}, author = {Afecto, E and Ponte, A and Fernandes, S and Silva, J and Gomes, C and Correia, J and Carvalho, J}, title = {Fecal microbiota transplantation in hepatic encephalopathy : a review of the current evidence and future perspectives.}, journal = {Acta gastro-enterologica Belgica}, volume = {84}, number = {1}, pages = {87-90}, doi = {10.51821/84.1.884}, pmid = {33639698}, issn = {1784-3227}, mesh = {Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; *Hepatic Encephalopathy/therapy ; Humans ; Liver Cirrhosis ; }, abstract = {Hepatic encephalopathy (HE) is a leading cause of hospitalization and morbimortality in advanced cirrhosis with limited therapeutic options available. Given the paramount role of gut microbiota in HE, and the efficacy of fecal microbiota transplantation (FMT) in other diseases, this review intends to summarize the evidence supporting the safety, efficacy and future perspectives of FMT in HE. Current evidence, despite being scarce, points towards FMT being a safe, effective and tolerable procedure in HE. Some unanswered questions remain about the optimal dose, the administration route, the long term effects and the selection of the optimal donor. Future trials, some of which are already underway, will provide us additional evidence and hopefully the necessary answers.}, }
@article {pmid33633264, year = {2021}, author = {Staley, C and Halaweish, H and Graiziger, C and Hamilton, MJ and Kabage, AJ and Galdys, AL and Vaughn, BP and Vantanasiri, K and Suryanarayanan, R and Sadowsky, MJ and Khoruts, A}, title = {Lower endoscopic delivery of freeze-dried intestinal microbiota results in more rapid and efficient engraftment than oral administration.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {4519}, pmid = {33633264}, issn = {2045-2322}, abstract = {Fecal microbiota transplantation (FMT) is a highly effective treatment for recurrent Clostridioides difficile infection (rCDI). However, standardization of FMT products is essential for its broad implementation into clinical practice. We have developed an oral preparation of freeze-dried, encapsulated microbiota, which is ~ 80% clinically effective, but results in delayed engraftment of donor bacteria relative to administration via colonoscopy. Our objective was to measure the engraftment potential of freeze-dried microbiota without the complexity of variables associated with oral administration. We compared engraftment of identical preparations and doses of freeze-dried microbiota following colonoscopic (9 patients) versus oral administration (18 patients). Microbiota were characterized by sequencing of the 16S rRNA gene, and engraftment was determined using the SourceTracker algorithm. Oligotyping analysis was done to provide high-resolution patterns of microbiota engraftment. Colonoscopic FMT was associated with greater levels of donor engraftment within days following the procedure (ANOVA P = 0.035) and specific increases in the relative abundances of donor Lachnospiraceae, Bacteroidaceae, and Porphyromonadaceae (P ≤ 0.033). Lower relative abundances of Bacteroidaceae, Lachnospiraceae, and Ruminococcaceae families were associated with clinical failures. These results suggest that further optimization of oral capsule FMT may improve its engraftment efficiency and clinical efficacy.}, }
@article {pmid33631102, year = {2021}, author = {Kao, D and Wong, K and Franz, R and Cochrane, K and Sherriff, K and Chui, L and Lloyd, C and Roach, B and Bai, AD and Petrof, EO and Allen-Vercoe, E}, title = {The effect of a microbial ecosystem therapeutic (MET-2) on recurrent Clostridioides difficile infection: a phase 1, open-label, single-group trial.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {6}, number = {4}, pages = {282-291}, doi = {10.1016/S2468-1253(21)00007-8}, pmid = {33631102}, issn = {2468-1253}, mesh = {Aged ; Clostridium Infections/*therapy ; Disease-Free Survival ; *Fecal Microbiota Transplantation ; Female ; Humans ; Male ; Middle Aged ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is highly effective for recurrent Clostridioides difficile infection but has inherent risks. Microbial Ecosystem Therapeutic 2 (MET-2) is an oral encapsulated formulation of 40 lyophilised bacterial species initially isolated from stool of a healthy donor, but subsequently manufactured independently of donors, eliminating potential risks introduced by changes in donor health. The aim of this study was to determine MET-2 activity, safety, and tolerability.<br><br>METHODS: This phase 1, open-label, single-group feasibility study was done in Alberta, Canada. The main inclusion criteria were mild to moderate C difficile infection and at least one episode of C difficile infection recurrence (ie, two episodes of C difficile infection) within 12 months. Initial daily treatment was ten oral capsules for 2 days, then three capsules for 8 days. If C difficile infection recurred, a higher dose was offered: 20 capsules for 2 days, then three capsules for 8 days. Patients were followed for adverse events and C difficile infection recurrence up to day 130. The primary outcome was absence of C difficile infection recurrence (fewer than three unformed bowel movements in 24 h persisting for at least 2 days) at day 40 by intention-to-treat analysis. Secondary outcomes were mortality or hospitalisation due to C difficile infection, infections attributed to treatment, nausea, abdominal pain, vomiting, or diarrhoea during treatment, quality of life (C difficile Health Related Quality of Life Questionnaire) before and after treatment, and engrafted MET-2 bacteria in patient stool. Absence of C difficile infection recurrence at day 130 was an exploratory outcome. This study is registered with ClinicalTrials.gov, NCT02865616 FINDINGS: Between Sept 19, 2018, and Feb 28, 2020, we enrolled 19 adult patients with at least two episodes of mild to moderate C difficile infection (median age 65 years [IQR 56-67]; 12 women [63%], seven men [37%]). Recurrent C difficile infection was absent at day 40 in 15 (79%) of 19 patients after initial treatment, increasing to 18 (95%) 40 days after retreatment. No mortality associated with C difficile infection, infections associated with MET-2 treatment, or other serious adverse events were observed. The most common self-limited, mild to moderate symptoms reported during treatment were diarrhoea in 12 (63%) of 19 patients and abdominal cramps in 12 (63%). After MET-2 treatment, quality of life improved significantly, as did alpha diversity in stool microbial composition (p=1·93×10-6). MET-2 associated taxa were found in greater abundance in most patients after treatment compared with baseline. 16 (84%) of 19 patients did not have recurrence of C difficile infection by day 130.<br><br>INTERPRETATION: MET-2 appears to be safe, efficacious, and well tolerated among patients with recurrent C difficile infection. Results must be validated in controlled studies.<br><br>FUNDING: NuBiyota.}, }
@article {pmid33628361, year = {2021}, author = {Du, D and Tang, W and Zhou, C and Sun, X and Wei, Z and Zhong, J and Huang, Z}, title = {Fecal Microbiota Transplantation Is a Promising Method to Restore Gut Microbiota Dysbiosis and Relieve Neurological Deficits after Traumatic Brain Injury.}, journal = {Oxidative medicine and cellular longevity}, volume = {2021}, number = {}, pages = {5816837}, pmid = {33628361}, issn = {1942-0994}, abstract = {Background: Traumatic brain injury (TBI) can induce persistent fluctuation in the gut microbiota makeup and abundance. The present study is aimed at determining whether fecal microbiota transplantation (FMT) can rescue microbiota changes and ameliorate neurological deficits after TBI in rats.<br><br>Methods: A controlled cortical impact (CCI) model was used to simulate TBI in male Sprague-Dawley rats, and FMT was performed for 7 consecutive days. 16S ribosomal RNA (rRNA) sequencing of fecal samples was performed to analyze the effects of FMT on gut microbiota. Modified neurological severity score and Morris water maze were used to evaluate neurobehavioral functions. Metabolomics was used to screen differential metabolites from the rat serum and ipsilateral brains. The oxidative stress indices were measured in the brain.<br><br>Results: TBI induced significance changes in the gut microbiome, including the alpha- and beta-bacterial diversity, as well as the microbiome composition at 8 days after TBI. On the other hand, FMT could rescue these changes and relieve neurological deficits after TBI. Metabolomics results showed that the level of trimethylamine (TMA) in feces and the level of trimethylamine N-oxide (TMAO) in the ipsilateral brain and serum was increased after TBI, while FMT decreased TMA levels in the feces, and TMAO levels in the ipsilateral brain and serum. Antioxidant enzyme methionine sulfoxide reductase A (MsrA) in the ipsilateral hippocampus was decreased after TBI but increased after FMT. In addition, FMT elevated SOD and CAT activities and GSH/GSSG ratio and diminished ROS, GSSG, and MDA levels in the ipsilateral hippocampus after TBI.<br><br>Conclusions: FMT can restore gut microbiota dysbiosis and relieve neurological deficits possibly through the TMA-TMAO-MsrA signaling pathway after TBI.}, }
@article {pmid33625548, year = {2021}, author = {Wang, J and Li, X and Wu, X and Wang, Z and Zhang, C and Cao, G and Liu, S and Yan, T}, title = {Gut microbiota alterations associated with antibody-mediated rejection after kidney transplantation.}, journal = {Applied microbiology and biotechnology}, volume = {105}, number = {6}, pages = {2473-2484}, pmid = {33625548}, issn = {1432-0614}, support = {No. 32000650//National Natural Science Foundation of China/ ; No. 192102310036//Henan Provincial Scientific and Technological Research Project/ ; No. 201702191//Henan Provincial Medical Scientific and Technological Research Project/ ; }, mesh = {*Gastrointestinal Microbiome ; Humans ; Kidney ; *Kidney Transplantation/adverse effects ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Antibody-mediated rejection (AMR) has become the major challenge for kidney transplantation, and the efficacy of existing therapies was limited to prevent AMR. Increasing evidences have demonstrated the link between gut microbiota alterations and allograft outcome. However, there has been no comprehensive analysis to profile the gut microbiota associated with AMR after kidney transplantation. We performed this study to characterize the gut microbiota possibly associated with AMR. Fecal specimens were collected from 24 kidney transplantation recipients with AMR and 29 controls. DNA extracted from the specimens was processed for 16S rRNA gene sequencing using Illumina MiSeq. Gut microbial community of recipients with AMR was significantly different from that of controls based on unweighted (P = 0.001) and weighted (P = 0.02) UniFrac distances, and the bacterial richness (observed species: P = 0.0448; Chao1 index: P = 0.0450; ACE index: P = 0.0331) significantly decreased in the AMR group. LEfSe showed that 1 phylum, 5 classes, 7 families, and 10 genera were increased, whereas 1 class, 2 order, 3 families, and 4 genera were decreased in the AMR group. Specific taxa such as Clostridiales could be potentially used as biomarkers to distinguish the recipients with AMR from the controls (AUC = 0.77). PICRUSt analysis illustrated that 16 functional pathways were with significantly different abundances in the AMR and control groups. Our findings provide a foundation for further investigation on the role of gut microbiota in AMR after kidney transplantation, and potentially support novel diagnostic biomarkers and therapeutic options for AMR. KEY POINTS: • Gut microbial community of kidney recipients with AMR was different from that of controls. • Clostridiales is a potential marker to distinguish recipients with AMR from controls.}, }
@article {pmid33623056, year = {2021}, author = {Berland, M and Cadiou, J and Levenez, F and Galleron, N and Quinquis, B and Thirion, F and Gauthier, F and Le Chatelier, E and Plaza Oñate, F and Schwintner, C and Rabot, S and Lepage, P and Ehrlich, D and Doré, J and Juste, C}, title = {High engraftment capacity of frozen ready-to-use human fecal microbiota transplants assessed in germ-free mice.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {4365}, pmid = {33623056}, issn = {2045-2322}, abstract = {The number of indications for fecal microbiota transplantation is expected to rise, thus increasing the needs for production of readily available frozen or freeze-dried transplants. Using shotgun metagenomics, we investigated the capacity of two novel human fecal microbiota transplants prepared in maltodextrin-trehalose solutions (abbreviated MD and TR for maltodextrin:trehalose, 3:1, w/w, and trehalose:maltodextrin 3:1, w/w, respectively), to colonize a germ-free born mouse model. Gavage with frozen-thawed MD or TR suspensions gave the taxonomic profiles of mouse feces that best resembled those obtained with the fresh inoculum (Spearman correlations based on relative abundances of metagenomic species around 0.80 and 0.75 for MD and TR respectively), while engraftment capacity of defrosted NaCl transplants most diverged (Spearman correlations around 0.63). Engraftment of members of the family Lachnospiraceae and Ruminoccocaceae was the most challenging in all groups of mice, being improved with MD and TR transplants compared to NaCl, but still lower than with the fresh preparation. Improvement of engraftment of this important group in maintaining health represents a challenge that could benefit from further research on fecal microbiota transplant manufacturing.}, }
@article {pmid33620078, year = {2021}, author = {Sheh, A}, title = {The Gastrointestinal Microbiota of the Common Marmoset (Callithrix jacchus).}, journal = {ILAR journal}, volume = {}, number = {}, pages = {}, doi = {10.1093/ilar/ilaa025}, pmid = {33620078}, issn = {1930-6180}, abstract = {The microbiota is heavily involved in both health and disease pathogenesis, but defining a normal, healthy microbiota in the common marmoset has been challenging. The aim of this review was to systematically review recent literature involving the gastrointestinal microbiome of common marmosets in health and disease. Twelve sources were included in this review. The gut microbiome composition was reviewed across institutions worldwide, and taxonomic shifts between healthy individuals were described. Unlike the human gut microbiome, which is dominated by Firmicutes and Bacteroidetes, the marmoset gut microbiome shows great plasticity across institutions, with 5 different phyla described as dominant in different healthy cohorts. Genera shared across institutions include Anaerobiospirillum, Bacteroides, Bifidobacterium, Collinsella, Fusobacterium, Megamonas, Megasphaera, Phascolarctobacterium, and Prevotella. Shifts in the abundance of Prevotella or Bifidobacterium or invasion by pathogens like Clostridium perfringens may be associated with disease. Changes in microbial composition have been described in healthy and diseased marmosets, but factors influencing the severe changes in microbial composition have not been established. Multi-institutional, prospective, and longitudinal studies that utilize multiple testing methodologies are required to determine sources of variability in the reporting of marmoset microbiomes. Furthermore, methods of microbial manipulation, whether by diet, enrichment, fecal microbiome transplantation, etc, need to be established to modulate and maintain robust and resilient microbiome communities in marmoset colonies and reduce the incidence of idiopathic gastrointestinal disease.}, }
@article {pmid33617596, year = {2021}, author = {Rungue, M and Melo, V and Martins, D and Campos, PC and Leles, G and Galvão, I and Mendes, V and Aganetti, M and Pedersen, Á and Assis, NRG and Santos, R and Cassali, GD and Godard, ALB and Martins, FS and Oliveira, SC and Vieira, AT}, title = {NLRP6-associated host microbiota composition impacts in the intestinal barrier to systemic dissemination of Brucella abortus.}, journal = {PLoS neglected tropical diseases}, volume = {15}, number = {2}, pages = {e0009171}, pmid = {33617596}, issn = {1935-2735}, support = {R01 AI116453/AI/NIAID NIH HHS/United States ; }, mesh = {Administration, Oral ; Animals ; Anti-Bacterial Agents/administration &amp; dosage ; Brucella abortus ; Brucellosis/microbiology/*physiopathology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Host-Pathogen Interactions ; Intestines/*microbiology/*physiopathology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Permeability ; Receptors, Cell Surface/genetics ; Specific Pathogen-Free Organisms ; }, abstract = {Brucella abortus is a Gram-negative bacterium responsible for a worldwide zoonotic infection-Brucellosis, which has been associated with high morbidity rate in humans and severe economic losses in infected livestock. The natural route of infection is through oral and nasal mucosa but the invasion process through host gut mucosa is yet to be understood. Studies have examined the role of NLRP6 (NOD-like receptor family pyrin domain-containing-6 protein) in gut homeostasis and defense against pathogens. Here, we investigated the impact of gut microbiota and NLRP6 in a murine model of Ba oral infection. Nlrp6-/- and wild-type (WT) mice were infected by oral gavage with Ba and tissues samples were collected at different time points. Our results suggest that Ba oral infection leads to significant alterations in gut microbiota. Moreover, Nlrp6-/- mice were more resistant to infection, with decreased CFU in the liver and reduction in gut permeability when compared to the control group. Fecal microbiota transplantation from WT and Nlrp6-/- into germ-free mice reflected the gut permeability phenotype from the donors. Additionally, depletion of gut microbiota by broad-spectrum-antibiotic treatment prevented Ba replication in WT while favoring bacterial growth in Nlrp6-/-. Finally, we observed higher eosinophils in the gut and leukocytes in the blood of infected Nlrp6-/- compared to WT-infected mice, which might be associated to the Nlrp6-/- resistance phenotype. Altogether, these results indicated that gut microbiota composition is the major factor involved in the initial stages of pathogen host replication and partially also by the resistance phenotype observed in Nlrp6 -/- mice regulating host inflammation against Ba infection.}, }
@article {pmid33617526, year = {2021}, author = {Henson, MA}, title = {Computational modeling of the gut microbiota reveals putative metabolic mechanisms of recurrent Clostridioides difficile infection.}, journal = {PLoS computational biology}, volume = {17}, number = {2}, pages = {e1008782}, pmid = {33617526}, issn = {1553-7358}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bacteria/genetics ; Bile Acids and Salts/metabolism ; *Clostridioides difficile ; Clostridium Infections/metabolism/*physiopathology ; Cluster Analysis ; Computer Simulation ; Enterobacteriaceae ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; Middle Aged ; Principal Component Analysis ; RNA, Ribosomal, 16S/*metabolism ; Reinfection ; Reproducibility of Results ; Young Adult ; }, abstract = {Approximately 30% of patients who have Clostridioides difficile infection (CDI) will suffer at least one incident of reinfection. While the underlying causes of CDI recurrence are poorly understood, interactions between C. difficile and commensal gut bacteria are thought to play an important role. In this study, an in silico pipeline was used to process 16S rRNA gene amplicon sequence data of 225 stool samples from 93 CDI patients into sample-specific models of bacterial community metabolism. Clustered metabolite production rates generated from post-diagnosis samples generated a high Enterobacteriaceae abundance cluster containing disproportionately large numbers of recurrent samples and patients. This cluster was predicted to have significantly reduced capabilities for secondary bile acid synthesis but elevated capabilities for aromatic amino acid catabolism. When applied to 16S sequence data of 40 samples from fecal microbiota transplantation (FMT) patients suffering from recurrent CDI and their stool donors, the community modeling method generated a high Enterobacteriaceae abundance cluster with a disproportionate large number of pre-FMT samples. This cluster also was predicted to exhibit reduced secondary bile acid synthesis and elevated aromatic amino acid catabolism. Collectively, these in silico predictions suggest that Enterobacteriaceae may create a gut environment favorable for C. difficile spore germination and/or toxin synthesis.}, }
@article {pmid33615992, year = {2021}, author = {Pham, VT and Fehlbaum, S and Seifert, N and Richard, N and Bruins, MJ and Sybesma, W and Rehman, A and Steinert, RE}, title = {Effects of colon-targeted vitamins on the composition and metabolic activity of the human gut microbiome- a pilot study.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1-20}, pmid = {33615992}, issn = {1949-0984}, abstract = {An increasing body of evidence has shown that gut microbiota imbalances are linked to diseases. Currently, the possibility of regulating gut microbiota to reverse these perturbations by developing novel therapeutic and preventive strategies is being extensively investigated. The modulatory effect of vitamins on the gut microbiome and related host health benefits remain largely unclear. We investigated the effects of colon-delivered vitamins A, B2, C, D, and E on the gut microbiota using a human clinical study and batch fermentation experiments, in combination with cell models for the assessment of barrier and immune functions. Vitamins C, B2, and D may modulate the human gut microbiome in terms of metabolic activity and bacterial composition. The most distinct effect was that of vitamin C, which significantly increased microbial alpha diversity and fecal short-chain fatty acids compared to the placebo. The remaining vitamins tested showed similar effects on microbial diversity, composition, and/or metabolic activity in vitro, but in varying degrees. Here, we showed that vitamins may modulate the human gut microbiome. Follow-up studies investigating targeted delivery of vitamins to the colon may help clarify the clinical significance of this novel concept for treating and preventing dysbiotic microbiota-related human diseases. Trial registration: ClinicalTrials.gov, NCT03668964. Registered 13 September 2018 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03668964.}, }
@article {pmid33613491, year = {2021}, author = {Qi, R and Zhang, Z and Wang, J and Qiu, X and Wang, Q and Yang, F and Huang, J and Liu, Z}, title = {Introduction of Colonic and Fecal Microbiota From an Adult Pig Differently Affects the Growth, Gut Health, Intestinal Microbiota and Blood Metabolome of Newborn Piglets.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {623673}, pmid = {33613491}, issn = {1664-302X}, abstract = {Microbiota transplantation is a rapid and effective method for changing and reshaping the intestinal microbiota and metabolic profile in humans and animals. This study compared the different influences of the introduction of fecal microbes and colonic microbes from a fat, adult pig in newborn pigs. Both colonic microbiota transplantation (CMT) and fecal microbiota transplantation (FMT) promoted growth and improved gut functions in suckling pigs up to weaning. FMT was more beneficial for body weight gain and body fat deposition in piglets, while CMT was more beneficial for intestinal health and mucosal immunity. 16S rDNA sequence analysis indicated that both CMT and FMT significantly increased the abundances of beneficial or functional bacteria, such as Lactobacillus and Prevotella_2 genera, in the piglets, and reduced the abundances of harmful bacteria, such as Escherichia-Shigella. Blood metabolome analysis showed that transplantation, especially FMT, enhanced lipid metabolism in piglets. In addition, while CMT also changed amino acid metabolism and increased anti-inflammatory metabolites such as 3-indoleacetic acid and 3-indolepropionic acid in piglets, FMT did not. Of note, FMT damaged the intestinal barrier of piglets to a certain extent and increased the levels of inflammatory factors in the blood that are potentially harmful to the health of pigs. Taken together, these results suggested that intestinal and fecal microbiota transplantations elicited similar but different physiological effects on young animals, so the application of microbiota transplantation in animal production requires the careful selection and evaluation of source bacteria.}, }
@article {pmid33609303, year = {2021}, author = {Barrow, F and Khan, S and Fredrickson, G and Wang, H and Dietsche, K and Parthiban, P and Robert, S and Kaiser, T and Winer, S and Herman, A and Adeyi, O and Mouzaki, M and Khoruts, A and Hogquist, KA and Staley, C and Winer, DA and Revelo, XS}, title = {Microbiota-Driven Activation of Intrahepatic B Cells Aggravates Nonalcoholic Steatohepatitis through Innate and Adaptive Signaling.}, journal = {Hepatology (Baltimore, Md.)}, volume = {}, number = {}, pages = {}, doi = {10.1002/hep.31755}, pmid = {33609303}, issn = {1527-3350}, abstract = {BACKGROUND AND AIMS: Nonalcoholic steatohepatitis (NASH) is rapidly becoming the leading cause of liver failure and indication for liver transplantation. Hepatic inflammation is a key feature of NASH but the immune pathways involved in this process are poorly understood. B lymphocytes are cells of the adaptive immune system that are critical regulators of immune responses. However, the role of B cells in the pathogenesis of NASH and the potential mechanisms leading to their activation in the liver are unclear.<br><br>APPROACH AND RESULTS: In this study, we report that NASH livers accumulate B cells with elevated pro-inflammatory cytokine secretion and antigen-presentation ability. Single-cell and bulk RNA sequencing of intrahepatic B cells from mice with NASH unveiled a transcriptional landscape that reflects their pro-inflammatory function. Accordingly, B cell-deficiency ameliorated NASH progression and adoptively transferring B cells from NASH livers recapitulates the disease. Mechanistically, B cell activation during NASH involves signaling through the innate adaptor myeloid differentiation primary response protein 88 (MyD88) as B cell-specific deletion of MyD88 reduced hepatic T cell-mediated inflammation and fibrosis, but not steatosis. In addition, activation of intrahepatic B cells implicates B cell receptor signaling, delineating a synergy between innate and adaptive mechanisms of antigen recognition. Furthermore, fecal microbiota transplantation of human NAFLD gut microbiotas into recipient mice promoted the progression of NASH by increasing the accumulation and activation of intrahepatic B cells, suggesting that gut microbial factors drive the pathogenic function of B cells during NASH.<br><br>CONCLUSION: Our findings reveal that a gut microbiota-driven activation of intrahepatic B cells leads to hepatic inflammation and fibrosis during the progression of NASH via innate and adaptive immune mechanisms.}, }
@article {pmid33608575, year = {2021}, author = {Kazemian, N and Ramezankhani, M and Sehgal, A and Khalid, FM and Kalkhoran, AHZ and Narayan, A and Wong, GK and Kao, D and Pakpour, S}, title = {Author Correction: The trans-kingdom battle between donor and recipient gut microbiome influences fecal microbiota transplantation outcome.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {4546}, doi = {10.1038/s41598-021-82644-z}, pmid = {33608575}, issn = {2045-2322}, }
@article {pmid33607299, year = {2021}, author = {Wang, B and Zhu, S and Liu, Z and Wei, H and Zhang, L and He, M and Pei, F and Zhang, J and Sun, Q and Duan, L}, title = {Increased Expression of Colonic Mucosal Melatonin in Patients with Irritable Bowel Syndrome Correlated with Gut Dysbiosis.}, journal = {Genomics, proteomics &amp; bioinformatics}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.gpb.2020.06.013}, pmid = {33607299}, issn = {2210-3244}, abstract = {Dysregulation of the gut microbiota/gut hormone axis contributes to the pathogenesis of irritable bowel syndrome (IBS). Melatonin plays a beneficial role in gut motility and immunity. However, altered expression of local mucosal melatonin in IBS and its relationship with the gut microbiota remain unclear. Therefore, we aimed to detect the colonic melatonin levels and microbiota profiles in patients with diarrhea-predominant IBS (IBS-D) and explore their relationship in germ-free (GF) rats and BON-1 cells. Thirty-two IBS-D patients and twenty-eight healthy controls (HCs) were recruited. Fecal specimens from IBS-D patients and HCs were separately transplanted into GF rats by gavage. The levels of colon mucosal melatonin were assessed by immunohistochemical methods, and fecal microbiota communities were analyzed using 16S rDNA sequencing. The effect of butyrate on melatonin synthesis in BON-1 cells was evaluated by ELISA. Melatonin levels were significantly increased and negatively correlated with visceral hypersensitivity in IBS-D patients. GF rats inoculated with fecal microbiota from IBS-D patients had high colonic melatonin levels. Butyrate-producing Clostridium cluster XIVa species, such as Roseburia species and Lachnospira species, were positively related to colonic mucosal melatonin expression. Butyrate significantly increased melatonin secretion in BON-1 cells. Increased melatonin expression may be an adaptive protective mechanism in the development of IBS-D. Moreover, some Clostridium cluster XIVa species could increase melatonin expression via butyrate production. Modulation of the gut hormone/gut microbiota axis offers a promising target of interest for IBS in the future.}, }
@article {pmid33605497, year = {2021}, author = {Zhang, LT and Westblade, LF and Iqbal, F and Taylor, MR and Chung, A and Satlin, MJ and Magruder, M and Edusei, E and Albakry, S and Botticelli, B and Robertson, A and Alston, T and Dadhania, DM and Lubetzky, M and Hirota, SA and Greenway, SC and Lee, JR}, title = {Gut microbiota profiles and fecal beta-glucuronidase activity in kidney transplant recipients with and without post-transplant diarrhea.}, journal = {Clinical transplantation}, volume = {35}, number = {5}, pages = {e14260}, doi = {10.1111/ctr.14260}, pmid = {33605497}, issn = {1399-0012}, support = {K23 AI124464/AI/NIAID NIH HHS/United States ; }, mesh = {Diarrhea ; *Gastrointestinal Microbiome ; Glucuronidase ; Humans ; *Kidney Transplantation ; RNA, Ribosomal, 16S ; }, abstract = {Post-transplant diarrhea is a common complication after solid organ transplantation and is frequently attributed to the widely prescribed immunosuppressant mycophenolate mofetil (MMF). Given recent work identifying the relationship between MMF toxicity and gut bacterial β-glucuronidase activity, we evaluated the relationship between gut microbiota composition, fecal β-glucuronidase activity, and post-transplant diarrhea. We recruited 97 kidney transplant recipients and profiled the gut microbiota in 273 fecal specimens using 16S rRNA gene sequencing. We further characterized fecal β-glucuronidase activity in a subset of this cohort. Kidney transplant recipients with post-transplant diarrhea had decreased gut microbial diversity and decreased relative gut abundances of 12 genera when compared to those without post-transplant diarrhea (adjusted p value < .15, Wilcoxon rank sum test). Among the kidney transplant recipients with post-transplant diarrhea, those with higher fecal β-glucuronidase activity had a more prolonged course of diarrhea (≥7 days) compared to patients with lower fecal β-glucuronidase activity (91% vs 40%, p = .02, Fisher's exact test). Our data reveal post-transplant diarrhea as a complex phenomenon with decreased gut microbial diversity and commensal gut organisms. This study further links commensal bacterial metabolism with an important clinical outcome measure, suggesting fecal β-glucuronidase activity could be a novel biomarker for gastrointestinal-related MMF toxicity.}, }
@article {pmid33602945, year = {2021}, author = {Serrano-Villar, S and Talavera-Rodríguez, A and Gosalbes, MJ and Madrid, N and Pérez-Molina, JA and Elliott, RJ and Navia, B and Lanza, VF and Vallejo, A and Osman, M and Dronda, F and Budree, S and Zamora, J and Gutiérrez, C and Manzano, M and Vivancos, MJ and Ron, R and Martínez-Sanz, J and Herrera, S and Ansa, U and Moya, A and Moreno, S}, title = {Fecal microbiota transplantation in HIV: A pilot placebo-controlled study.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {1139}, pmid = {33602945}, issn = {2041-1723}, mesh = {Biodiversity ; Biomarkers/blood ; Discriminant Analysis ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; HIV Infections/blood/*microbiology/*therapy ; Humans ; Male ; Middle Aged ; Phylogeny ; Pilot Projects ; Placebos ; Tissue Donors ; }, abstract = {Changes in the microbiota have been linked to persistent inflammation during treated HIV infection. In this pilot double-blind study, we study 30 HIV-infected subjects on antiretroviral therapy (ART) with a CD4/CD8 ratio < 1 randomized to either weekly fecal microbiota capsules or placebo for 8 weeks. Stool donors were rationally selected based on their microbiota signatures. We report that fecal microbiota transplantation (FMT) is safe, not related to severe adverse events, and attenuates HIV-associated dysbiosis. FMT elicits changes in gut microbiota structure, including significant increases in alpha diversity, and a mild and transient engraftment of donor's microbiota during the treatment period. The greater engraftment seems to be achieved by recent antibiotic use before FMT. The Lachnospiraceae and Ruminococcaceae families, which are typically depleted in people with HIV, are the taxa more robustly engrafted across time-points. In exploratory analyses, we describe a significant amelioration in the FMT group in intestinal fatty acid-binding protein (IFABP), a biomarker of intestinal damage that independently predicts mortality. Gut microbiota manipulation using a non-invasive and safe strategy of FMT delivery is feasible and deserves further investigation. Trial number: NCT03008941.}, }
@article {pmid33598642, year = {2021}, author = {Hua, H and Zhang, Y and Zhao, F and Chen, K and Wu, T and Liu, Q and Huang, S and Zhang, A and Jia, Z}, title = {Celastrol inhibits intestinal lipid absorption by reprofiling the gut microbiota to attenuate high-fat diet-induced obesity.}, journal = {iScience}, volume = {24}, number = {2}, pages = {102077}, pmid = {33598642}, issn = {2589-0042}, abstract = {Celastrol, a compound extracted from traditional Chinese medicine, has been reported as a potent anti-obesity agent with controversial mechanisms. Here both C57BL/6J and leptin-deficient (ob/ob) mice fed a high-fat diet (HFD) displayed body weight loss after celastrol therapy, opposing the previous viewpoint that celastrol improves obesity by sensitizing leptin signaling. More importantly, celastrol downregulated lipid transporters in the intestine, increased lipid excretion in feces, and reduced body weight gain in HFD mice. Meanwhile, analysis of gut microbiota revealed that celastrol altered the gut microbiota composition in HFD-fed mice, and modulating gut microbiota by antibiotics or fecal microbiota transplantation blocked the celastrol effect on intestinal lipid transport and body weight gain, suggesting a critical role of the gut microbiota composition in mediating the anti-obesity role of celastrol under HFD. Together, the findings revealed that celastrol reduces intestinal lipid absorption to antagonize obesity by resetting the gut microbiota profile under HFD feeding.}, }
@article {pmid33598269, year = {2021}, author = {Zeng, J and Peng, L and Zheng, W and Huang, F and Zhang, N and Wu, D and Yang, Y}, title = {Fecal microbiota transplantation for rheumatoid arthritis: A case report.}, journal = {Clinical case reports}, volume = {9}, number = {2}, pages = {906-909}, pmid = {33598269}, issn = {2050-0904}, abstract = {No previous case of using fecal microbiota transplantation (FMT) to treat rheumatoid arthritis (RA) has been reported. We report a case of a patient with refractory RA successfully treated with FMT indicating that FMT may have a good therapeutic effect on RA.}, }
@article {pmid33595467, year = {2021}, author = {Shivaji, S}, title = {A systematic review of gut microbiome and ocular inflammatory diseases: Are they associated?.}, journal = {Indian journal of ophthalmology}, volume = {69}, number = {3}, pages = {535-542}, pmid = {33595467}, issn = {1998-3689}, mesh = {Bacteria ; Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; *Keratitis ; *Microbiota ; }, abstract = {The primary focus of this review was to establish the possible association of dysbiotic changes in the gut bacterial microbiomes with both intestinal and extra-intestinal diseases with emphasis on ocular diseases such as bacterial keratitis, fungal keratitis, uveitis, age-related macular degeneration, and ocular mucosal diseases. For this particular purpose, a systematic search was conducted using PubMed and Google Scholar for publications related to gut microbiome and human health (using the keywords: gut microbiome, ocular disease, dysbiosis, keratitis, uveitis, and AMD). The predictions are that microbiome studies would help to unravel dysbiotic changes in the gut bacterial microbiome at the taxonomic and functional level and thus form the basis to mitigate inflammatory diseases of the eye by using nutritional supplements or fecal microbiota transplantation.}, }
@article {pmid33595259, year = {2021}, author = {Li, S and Guo, H and Xu, X and Hua, R and Zhao, Q and Li, J and Lv, J and Li, J}, title = {Therapeutic Methods for Gut Microbiota Modification in Lipopolysaccharide-Associated Encephalopathy.}, journal = {Shock (Augusta, Ga.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/SHK.0000000000001758}, pmid = {33595259}, issn = {1540-0514}, abstract = {OBJECTIVE: To compare the efficacy of four therapeutic methods to modify gut microbiota dysbiosis and brain dysfunction in septic rats.<br><br>METHODS: Rats were treated with fecal microbiota transplantation, prebiotics, probiotics, and synbiotics after exposure to lipopolysaccharide. The diversity and composition of gut microbiota, electroencephalogram values, and the concentrations of TNF-α, IL-1β, and IL-6 in the cortex were analyzed.<br><br>RESULTS: Fecal microbiota transplantation was the most efficacious method to restore intestinal microbial diversity and exert the best corrective effects in modulating microbial composition in septic rats. More interestingly, fecal microbiota transplantation exerted the best protective effects in brain dysfunction in septic rats.<br><br>CONCLUSION: Among the four methods, fecal microbiota transplantation was the most useful method to modify the dysbiosis of intestinal microbiota and improve brain function in septic rats. These findings reveal the protective consequence of microbiota modification, and the findings suggest opportunities to improve brain function in sepsis.}, }
@article {pmid33593727, year = {2021}, author = {Brooks, EF and Bhatt, AS}, title = {The gut microbiome: a missing link in understanding the gastrointestinal manifestations of COVID-19?.}, journal = {Cold Spring Harbor molecular case studies}, volume = {7}, number = {2}, pages = {}, pmid = {33593727}, issn = {2373-2873}, mesh = {Abdominal Pain/diagnosis/*etiology/microbiology/pathology ; Animals ; COVID-19/*complications/diagnosis/microbiology/pathology ; Diarrhea/diagnosis/*etiology/microbiology/pathology ; Feces/microbiology/virology ; *Gastrointestinal Microbiome ; Humans ; Nausea/diagnosis/*etiology/microbiology/pathology ; SARS-CoV-2/isolation &amp; purification ; Vomiting/diagnosis/*etiology/microbiology/pathology ; }, abstract = {Coronavirus disease 2019 (COVID-19), which is caused by infection with SARS-CoV-2, presents with a broad constellation of both respiratory and nonrespiratory symptoms, although it is primarily considered a respiratory disease. Gastrointestinal symptoms-including nausea, abdominal pain, vomiting, and diarrhea-rank chief among these. When coupled with the presence of viral RNA in fecal samples, the presence of gastrointestinal symptoms raises relevant questions regarding whether SARS-CoV-2 can productively infect the upper or lower gastrointestinal tract. Despite the well-documented prevalence of gastrointestinal symptoms and the high rate of SARS-CoV-2 fecal RNA shedding, the biological, clinical, and epidemiological relevance of these findings is unclear. Furthermore, the isolation of replication-competent virus from fecal samples has not been reproducibly and rigorously demonstrated. Although SARS-CoV-2 shedding likely occurs in a high proportion of patients, gastrointestinal symptoms affect only a subset of individuals. Herein, we summarize what is known about gastrointestinal symptoms and fecal viral shedding in COVID-19, explore the role of the gut microbiome in other respiratory diseases, speculate on the role of the gut microbiota in COVID-19, and discuss potential future directions. Taking these concepts together, we propose that studying gut microbiota perturbations in COVID-19 will enhance our understanding of the symptomology and pathophysiology of this novel devastating disease.}, }
@article {pmid33593430, year = {2021}, author = {Langdon, A and Schwartz, DJ and Bulow, C and Sun, X and Hink, T and Reske, KA and Jones, C and Burnham, CD and Dubberke, ER and Dantas, G and , }, title = {Microbiota restoration reduces antibiotic-resistant bacteria gut colonization in patients with recurrent Clostridioides difficile infection from the open-label PUNCH CD study.}, journal = {Genome medicine}, volume = {13}, number = {1}, pages = {28}, pmid = {33593430}, issn = {1756-994X}, support = {1U1CI000033 301/CC/CDC HHS/United States ; R01AI123394//National Institute of Allergy and Infectious Diseases/ ; R01HD092414//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; TL1 TR000449/NH/NIH HHS/United States ; St. Jude Fellowship in Basic Research//Pediatric Infectious Diseases Society/ ; T32 HG000045/HG/NHGRI NIH HHS/United States ; }, abstract = {BACKGROUND: Once antibiotic-resistant bacteria become established within the gut microbiota, they can cause infections in the host and be transmitted to other people and the environment. Currently, there are no effective modalities for decreasing or preventing colonization by antibiotic-resistant bacteria. Intestinal microbiota restoration can prevent Clostridioides difficile infection (CDI) recurrences. Another potential application of microbiota restoration is suppression of non-C. difficile multidrug-resistant bacteria and overall decrease in the abundance of antibiotic resistance genes (the resistome) within the gut microbiota. This study characterizes the effects of RBX2660, a microbiota-based investigational therapeutic, on the composition and abundance of the gut microbiota and resistome, as well as multidrug-resistant organism carriage, after delivery to patients suffering from recurrent CDI.<br><br>METHODS: An open-label, multi-center clinical trial in 11 centers in the USA for the safety and efficacy of RBX2660 on recurrent CDI was conducted. Fecal specimens from 29 of these subjects with recurrent CDI who received either one (N = 16) or two doses of RBX2660 (N = 13) were analyzed secondarily. Stool samples were collected prior to and at intervals up to 6 months post-therapy and analyzed in three ways: (1) 16S rRNA gene sequencing for microbiota taxonomic composition, (2) whole metagenome shotgun sequencing for functional pathways and antibiotic resistome content, and (3) selective and differential bacterial culturing followed by isolate genome sequencing to longitudinally track multidrug-resistant organisms.<br><br>RESULTS: Successful prevention of CDI recurrence with RBX2660 correlated with taxonomic convergence of patient microbiota to the donor microbiota as measured by weighted UniFrac distance. RBX2660 dramatically reduced the abundance of antibiotic-resistant Enterobacteriaceae in the 2 months after administration. Fecal antibiotic resistance gene carriage decreased in direct relationship to the degree to which donor microbiota engrafted.<br><br>CONCLUSIONS: Microbiota-based therapeutics reduce resistance gene abundance and resistant organisms in the recipient gut microbiome. This approach could potentially reduce the risk of infections caused by resistant organisms within the patient and the transfer of resistance genes or pathogens to others.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov, NCT01925417 ; registered on August 19, 2013.}, }
@article {pmid33593429, year = {2021}, author = {Moshkelgosha, S and Verhasselt, HL and Masetti, G and Covelli, D and Biscarini, F and Horstmann, M and Daser, A and Westendorf, AM and Jesenek, C and Philipp, S and Diaz-Cano, S and Banga, JP and Michael, D and Plummer, S and Marchesi, JR and Eckstein, A and Ludgate, M and Berchner-Pfannschmidt, U and , }, title = {Modulating gut microbiota in a mouse model of Graves' orbitopathy and its impact on induced disease.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {45}, pmid = {33593429}, issn = {2049-2618}, mesh = {Animals ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Graves Ophthalmopathy/immunology/metabolism/*microbiology/pathology ; Humans ; Mice ; Mice, Inbred BALB C ; }, abstract = {BACKGROUND: Graves' disease (GD) is an autoimmune condition in which autoantibodies to the thyrotropin receptor (TSHR) cause hyperthyroidism. About 50% of GD patients also have Graves' orbitopathy (GO), an intractable disease in which expansion of the orbital contents causes diplopia, proptosis and even blindness. Murine models of GD/GO, developed in different centres, demonstrated significant variation in gut microbiota composition which correlated with TSHR-induced disease heterogeneity. To investigate whether correlation indicates causation, we modified the gut microbiota to determine whether it has a role in thyroid autoimmunity. Female BALB/c mice were treated with either vancomycin, probiotic bacteria, human fecal material transfer (hFMT) from patients with severe GO or ddH2O from birth to immunization with TSHR-A subunit or beta-galactosidase (βgal; age ~ 6 weeks). Incidence and severity of GD (TSHR autoantibodies, thyroid histology, thyroxine level) and GO (orbital fat and muscle histology), lymphocyte phenotype, cytokine profile and gut microbiota were analysed at sacrifice (~ 22 weeks).<br><br>RESULTS: In ddH2O-TSHR mice, 84% had pathological autoantibodies, 67% elevated thyroxine, 77% hyperplastic thyroids and 70% orbital pathology. Firmicutes were increased, and Bacteroidetes reduced relative to ddH2O-βgal; CCL5 was increased. The random forest algorithm at the genus level predicted vancomycin treatment with 100% accuracy but 74% and 70% for hFMT and probiotic, respectively. Vancomycin significantly reduced gut microbiota richness and diversity compared with all other groups; the incidence and severity of both GD and GO also decreased; reduced orbital pathology correlated positively with Akkermansia spp. whilst IL-4 levels increased. Mice receiving hFMT initially inherited their GO donors' microbiota, and the severity of induced GD increased, as did the orbital brown adipose tissue volume in TSHR mice. Furthermore, genus Bacteroides, which is reduced in GD patients, was significantly increased by vancomycin but reduced in hFMT-treated mice. Probiotic treatment significantly increased CD25+ Treg cells in orbital draining lymph nodes but exacerbated induced autoimmune hyperthyroidism and GO.<br><br>CONCLUSIONS: These results strongly support a role for the gut microbiota in TSHR-induced disease. Whilst changes to the gut microbiota have a profound effect on quantifiable GD endocrine and immune factors, the impact on GO cellular changes is more nuanced. The findings have translational potential for novel, improved treatments. Video abstract.}, }
@article {pmid33580895, year = {2021}, author = {Wilmes, L and Collins, JM and O'Riordan, KJ and O'Mahony, SM and Cryan, JF and Clarke, G}, title = {Of bowels, brain and behavior: A role for the gut microbiota in psychiatric comorbidities in irritable bowel syndrome.}, journal = {Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society}, volume = {33}, number = {3}, pages = {e14095}, doi = {10.1111/nmo.14095}, pmid = {33580895}, issn = {1365-2982}, abstract = {BACKGROUND: The gastrointestinal microbiota has emerged as a key regulator of gut-brain axis signalling with important implications for neurogastroenterology. There is continuous bidirectional communication between the gut and the brain facilitated by neuronal, endocrine, metabolic, and immune pathways. The microbiota influences these signalling pathways via several mechanisms. Studies have shown compositional and functional alterations in the gut microbiota in stress-related psychiatric disorders. Gut microbiota reconfigurations are also a feature of irritable bowel syndrome (IBS), a gut-brain axis disorder sharing high levels of psychiatric comorbidity including both anxiety and depression. It remains unclear how the gut microbiota alterations in IBS align with both core symptoms and these psychiatric comorbidities.<br><br>METHODS: In this review, we highlight common and disparate features of these microbial signatures as well as the associated gut-brain axis signalling pathways. Studies suggest that patients with either IBS, depression or anxiety, alone or comorbid, present with alterations in gut microbiota composition and harbor immune, endocrine, and serotonergic system alterations relevant to the common pathophysiology of these comorbid conditions.<br><br>KEY RESULTS: Research has illustrated the utility of fecal microbiota transplantation in animal models, expanding the evidence base for a potential causal role of disorder-specific gut microbiota compositions in symptom set expression. Moreover, an exciting study by Constante and colleagues in this issue highlights the possibility of counteracting this microbiota-associated aberrant behavioral phenotype with a probiotic yeast, Saccharomyces boulardii CNCM I-745.<br><br>CONCLUSIONS AND INFERENCES: Such data highlights the potential for therapeutic targeting of the gut microbiota as a valuable strategy for the management of comorbid psychiatric symptoms in IBS.}, }
@article {pmid33579424, year = {2021}, author = {Golonka, RM and Vijay-Kumar, M}, title = {Atypical immunometabolism and metabolic reprogramming in liver cancer: Deciphering the role of gut microbiome.}, journal = {Advances in cancer research}, volume = {149}, number = {}, pages = {171-255}, doi = {10.1016/bs.acr.2020.10.004}, pmid = {33579424}, issn = {2162-5557}, support = {R01 CA219144/CA/NCI NIH HHS/United States ; }, abstract = {Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related mortality worldwide. Much recent research has delved into understanding the underlying molecular mechanisms of HCC pathogenesis, which has revealed to be heterogenous and complex. Two major hallmarks of HCC include: (i) a hijacked immunometabolism and (ii) a reprogramming in metabolic processes. We posit that the gut microbiota is a third component in an entanglement triangle contributing to HCC progression. Besides metagenomic studies highlighting the diagnostic potential in the gut microbiota profile, recent research is pinpointing the gut microbiota as an instigator, not just a mere bystander, in HCC. In this chapter, we discuss mechanistic insights on atypical immunometabolism and metabolic reprogramming in HCC, including the examination of tumor-associated macrophages and neutrophils, tumor-infiltrating lymphocytes (e.g., T-cell exhaustion, regulatory T-cells, natural killer T-cells), the Warburg effect, rewiring of the tricarboxylic acid cycle, and glutamine addiction. We further discuss the potential involvement of the gut microbiota in these characteristics of hepatocarcinogenesis. An immediate highlight is that microbiota metabolites (e.g., short chain fatty acids, secondary bile acids) can impair anti-tumor responses, which aggravates HCC. Lastly, we describe the rising 'new era' of immunotherapies (e.g., immune checkpoint inhibitors, adoptive T-cell transfer) and discuss for the potential incorporation of gut microbiota targeted therapeutics (e.g., probiotics, fecal microbiota transplantation) to alleviate HCC. Altogether, this chapter invigorates for continuous research to decipher the role of gut microbiome in HCC from its influence on immunometabolism and metabolic reprogramming.}, }
@article {pmid33578974, year = {2021}, author = {Lee, JJ and Yong, D and Suk, KT and Kim, DJ and Woo, HJ and Lee, SS and Kim, BS}, title = {Alteration of Gut Microbiota in Carbapenem-Resistant Enterobacteriaceae Carriers during Fecal Microbiota Transplantation According to Decolonization Periods.}, journal = {Microorganisms}, volume = {9}, number = {2}, pages = {}, pmid = {33578974}, issn = {2076-2607}, support = {2019R1I1A3A01060465//Ministry of Education, Korea/ ; 2020R1A6A1A03043026//Ministry of Education, Korea/ ; NRF-2017M3A9F3043837//Ministry of Science, ICT and Future Planning/ ; HURF-2015-32//Hallym University/ ; }, abstract = {Fecal microbiota transplantation (FMT) has been suggested as an alternative therapeutic option to decolonize carbapenem-resistant Enterobacteriaceae (CRE). However, the analysis of gut microbiota alteration in CRE carriers during FMT is still limited. Here, gut microbiota changes in CRE carriers were evaluated during FMT according to decolonization periods. The decolonization of 10 CRE carriers was evaluated after FMT, using serial consecutive rectal swab cultures. Alterations of gut microbiota before and after FMT (56 serial samples) were analyzed using high-throughput sequencing. The decolonization rates of CRE carriers were 40%, 50%, and 90% within 1, 3 and 5 months after initial FMT, respectively. Gut microbiota significantly changed after FMT (p = 0.003). Microbiota alteration was different between the early decolonization carriers (EDC) and late decolonization carriers (LDC). Microbiota convergence in carriers to donors was detected in EDC within 4 weeks, and keystone genera within the Bacteroidetes were found in the gut microbiota of EDC before FMT. The relative abundance of Klebsiella was lower in EDC than in LDC, before and after FMT. Our results indicate that FMT is a potential option for CRE decolonization. The gut microbiota of CRE carriers could be used to predict decolonization timing after FMT, and determine repeated FMT necessity.}, }
@article {pmid33578830, year = {2021}, author = {Heo, G and Lee, Y and Im, E}, title = {Interplay between the Gut Microbiota and Inflammatory Mediators in the Development of Colorectal Cancer.}, journal = {Cancers}, volume = {13}, number = {4}, pages = {}, pmid = {33578830}, issn = {2072-6694}, support = {2019R1A2C1010536//National Research Foundation of Korea/ ; }, abstract = {Inflammatory mediators modulate inflammatory pathways during the development of colorectal cancer. Inflammatory mediators secreted by both immune and tumor cells can influence carcinogenesis, progression, and tumor metastasis. The gut microbiota, which colonize the entire intestinal tract, especially the colon, are closely linked to colorectal cancer through an association with inflammatory mediators such as tumor necrosis factor, nuclear factor kappa B, interleukins, and interferons. This association may be a potential therapeutic target, since therapeutic interventions targeting the gut microbiota have been actively investigated in both the laboratory and in clinics and include fecal microbiota transplantation and probiotics.}, }
@article {pmid33577875, year = {2021}, author = {Fujimoto, K and Kimura, Y and Allegretti, JR and Yamamoto, M and Zhang, YZ and Katayama, K and Tremmel, G and Kawaguchi, Y and Shimohigoshi, M and Hayashi, T and Uematsu, M and Yamaguchi, K and Furukawa, Y and Akiyama, Y and Yamaguchi, R and Crowe, SE and Ernst, PB and Miyano, S and Kiyono, H and Imoto, S and Uematsu, S}, title = {Functional Restoration of Bacteriomes and Viromes by Fecal Microbiota Transplantation.}, journal = {Gastroenterology}, volume = {160}, number = {6}, pages = {2089-2102.e12}, doi = {10.1053/j.gastro.2021.02.013}, pmid = {33577875}, issn = {1528-0012}, abstract = {BACKGROUND &amp; AIMS: Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridioides difficile infection (rCDI). However, the overall mechanisms underlying FMT success await comprehensive elucidation, and the safety of FMT has recently become a serious concern because of the occurrence of drug-resistant bacteremia transmitted by FMT. We investigated whether functional restoration of the bacteriomes and viromes by FMT could be an indicator of successful FMT.<br><br>METHODS: The human intestinal bacteriomes and viromes from 9 patients with rCDI who had undergone successful FMT and their donors were analyzed. Prophage-based and CRISPR spacer-based host bacteria-phage associations in samples from recipients before and after FMT and in donor samples were examined. The gene functions of intestinal microorganisms affected by FMT were evaluated.<br><br>RESULTS: Metagenomic sequencing of both the viromes and bacteriomes revealed that FMT does change the characteristics of intestinal bacteriomes and viromes in recipients after FMT compared with those before FMT. In particular, many Proteobacteria, the fecal abundance of which was high before FMT, were eliminated, and the proportion of Microviridae increased in recipients. Most temperate phages also behaved in parallel with the host bacteria that were altered by FMT. Furthermore, the identification of bacterial and viral gene functions before and after FMT revealed that some distinctive pathways, including fluorobenzoate degradation and secondary bile acid biosynthesis, were significantly represented.<br><br>CONCLUSIONS: The coordinated action of phages and their host bacteria restored the recipients' intestinal flora. These findings show that the restoration of intestinal microflora functions reflects the success of FMT.}, }
@article {pmid33576793, year = {2021}, author = {Ducarmon, QR and Kuijper, EJ and Olle, B}, title = {Opportunities and Challenges in Development of Live Biotherapeutic Products to Fight Infections.}, journal = {The Journal of infectious diseases}, volume = {223}, number = {Supplement_3}, pages = {S283-S289}, doi = {10.1093/infdis/jiaa779}, pmid = {33576793}, issn = {1537-6613}, abstract = {Treatment of bacterial infections with broad-spectrum antibiotics is a strategy severely limited by the decreased ability of the perturbed resident microbiota to control expansion of antibiotic-resistant pathogens. Live biotherapeutic products (LBPs) could provide an alternative to antibiotics in infection control by restoring gut colonization resistance and controlling expansion of resistant strains, an important therapeutic need not being addressed with existing anti-infective drug modalities. We review opportunities and challenges in developing LBPs for multidrug-resistant organisms colonization and infection control, with a focus on commercial fecal microbiota transplantation-like products and defined bacterial consortia, and spanning considerations related to availability of models for rational drug candidate selection and dose regimen selection, good manufacturing practice, intellectual property, and commercial viability.}, }
@article {pmid33575297, year = {2021}, author = {Saha, S and Khanna, S}, title = {Stool banking for fecal microbiota transplantation: ready for prime time?.}, journal = {Hepatobiliary surgery and nutrition}, volume = {10}, number = {1}, pages = {110-112}, pmid = {33575297}, issn = {2304-3881}, }
@article {pmid33575288, year = {2021}, author = {Sheng, L and Jena, PK and Hu, Y and Wan, YY}, title = {Age-specific microbiota in altering host inflammatory and metabolic signaling as well as metabolome based on the sex.}, journal = {Hepatobiliary surgery and nutrition}, volume = {10}, number = {1}, pages = {31-48}, pmid = {33575288}, issn = {2304-3881}, support = {R01 CA222490/CA/NCI NIH HHS/United States ; U01 CA179582/CA/NCI NIH HHS/United States ; U2C DK092993/DK/NIDDK NIH HHS/United States ; }, abstract = {Background: Metabolism is sex-different, and the direct link between gut microbiota and aging-associated metabolic changes needs to be established in both sexes.<br><br>Methods: Gene expression, metabolic and inflammatory signaling, gut microbiota profile, and metabolome were studied during aging and after fecal microbiota transplantation (FMT) in mice of both sexes.<br><br>Results: Our data revealed young female mice and aged male mice were the most insulin sensitive and resistant group, respectively. In addition, aging reduced sex difference in insulin sensitivity. Such age- and sex-dependent metabolic phenotypes were accompanied by shifted gut microbiota profile and altered abundance of bacterial genes that produce butyrate, propionate, and bile acids. After receiving feces from the aged males (AFMT), the most insulin-resistant group, recipients of both sexes had increased hepatic inflammation and serum endotoxin. However, AFMT only increased insulin resistance in female mice and abolished sex difference in insulin sensitivity. Additionally, such changes were accompanied by narrowed sex difference in metabolome. Metabolomics data revealed that age-associated insulin resistance in males was accompanied by increased sugar alcohols and dicarboxylic acids as well as reduced aromatic and branched-chain amino acids. Further, receiving feces from the young females (YFMT), the most insulin-sensitive group, reduced body weight and fasting blood glucose in male recipients and improved insulin sensitivity in females, leading to enhanced sex differences in insulin sensitivity and metabolome.<br><br>Conclusions: Aging systemically affected inflammatory and metabolic signaling based on the sex. Gut microbiome is age and sex-specific, which affects inflammation and metabolism in a sex-dependent manner.}, }
@article {pmid33573867, year = {2021}, author = {Ciernikova, S and Kasperova, B and Drgona, L and Smolkova, B and Stevurkova, V and Mego, M}, title = {Targeting the gut microbiome: An emerging trend in hematopoietic stem cell transplantation.}, journal = {Blood reviews}, volume = {48}, number = {}, pages = {100790}, doi = {10.1016/j.blre.2020.100790}, pmid = {33573867}, issn = {1532-1681}, abstract = {Mounting evidence has demonstrated the critical role of the gut microbiome in different cancer treatment modalities showing intensive crosstalk between microbiota and the host immune system. In cancer patients receiving hematopoietic stem cell transplantation (HSCT), conditioning regimens including chemotherapy, radiotherapy, and immunosuppressive therapy, as well as antimicrobial prophylaxis, result in intestinal barrier disruption and massive changes in microbiota composition. According to clinical studies, a drastic loss of microbial diversity during HSCT is associated with enhanced pro-inflammatory immune response and an increased risk of transplant-related complications such as graft-versus-host disease (GvHD) and mortality. In this review, we outline the current understanding of the role of microbiota diversity in the patient response to cancer therapies and highlight the impact of changes in the gut microbiome on clinical outcomes in post-HSCT patients. Moreover, the therapeutic implications of microbiota modulation by probiotics, prebiotics, and fecal microbiota transplantation (FMT) in hematologic cancer patients receiving HSCT are discussed.}, }
@article {pmid33572016, year = {2021}, author = {Chauhan, A and Apostolov, R and van Langenberg, D and Garg, M}, title = {Faecal microbiota transplantation for recurrent Clostridioides difficile infection: an Australian experience - effective, safe, yet room for improvement.}, journal = {Internal medicine journal}, volume = {51}, number = {1}, pages = {106-110}, doi = {10.1111/imj.15162}, pmid = {33572016}, issn = {1445-5994}, mesh = {Australia ; Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/diagnosis/therapy ; Fecal Microbiota Transplantation ; Humans ; Recurrence ; Treatment Outcome ; }, abstract = {Faecal microbiota transplantation (FMT) is reportedly effective and safe for the management of recurrent or refractory Clostridioides difficile infection (CDI), yet real-world data of outcomes of FMT in Australia are limited. In this series, FMT safely resulted in resolution of CDI in 19 patients with reduced healthcare utilisation after 25 FMT, but one patient was diagnosed with an anti-nuclear antibody-positive constitutional illness and Hashimoto thyroiditis following FMT. Further prospective evaluation of the utility of FMT earlier in CDI treatment algorithms to minimise cost and morbidity, and recipient follow up for immune-mediated conditions, is required.}, }
@article {pmid33571456, year = {2021}, author = {Ianiro, G and Mullish, BH and Hvas, CL and Segal, JP and Kuijper, EJ and Costello, SP and Kelly, CR and Allegretti, JR and Fischer, M and Iqbal, TH and Satokari, R and Kao, D and van Prehn, J and Ng, SC and Bibbò, S and Baunwall, SMD and Quraishi, MN and Sokol, H and Zhang, F and Keller, J and Masucci, L and Quaranta, G and Kassam, Z and Sanguinetti, M and Tilg, H and Gasbarrini, A and Cammarota, G}, title = {SARS-CoV-2 vaccines and donor recruitment for FMT.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {6}, number = {4}, pages = {264-266}, doi = {10.1016/S2468-1253(21)00032-7}, pmid = {33571456}, issn = {2468-1253}, mesh = {COVID-19/*prevention &amp; control/transmission ; *COVID-19 Vaccines ; Donor Selection/*organization &amp; administration ; *Fecal Microbiota Transplantation ; Humans ; }, }
@article {pmid33571442, year = {2021}, author = {Rebeck, ON and Dantas, G and Schwartz, DJ}, title = {Improving ICI outcomes with a little help from my microbial friends.}, journal = {Cell host &amp; microbe}, volume = {29}, number = {2}, pages = {155-157}, doi = {10.1016/j.chom.2021.01.012}, pmid = {33571442}, issn = {1934-6069}, abstract = {Gut microbiome composition correlates with responsiveness to immune checkpoint inhibitor therapy. In a recent study in Science, Baruch et al. manipulated gut microbiome composition in patients with refractory metastatic melanoma using fecal microbiota transplants. Fecal microbiota transplant was safe and partially effective in inducing remission in refractory patients.}, }
@article {pmid33570405, year = {2021}, author = {Huang, Y and Yang, Q and Mi, X and Qiu, L and Tao, X and Zhang, Z and Xia, J and Wu, Q and Wei, H}, title = {Ripened Pu-erh Tea Extract Promotes Gut Microbiota Resilience against Dextran Sulfate Sodium Induced Colitis.}, journal = {Journal of agricultural and food chemistry}, volume = {69}, number = {7}, pages = {2190-2203}, doi = {10.1021/acs.jafc.0c07537}, pmid = {33570405}, issn = {1520-5118}, mesh = {Animals ; *Colitis/chemically induced/drug therapy ; Dextran Sulfate/toxicity ; *Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; Plant Extracts ; RNA, Ribosomal, 16S/genetics ; Tea ; }, abstract = {Ripened Pu-erh tea (RPT) has been shown to be an effective natural ingredient to defend against experimentally induced colitis. We hypothesized that RPT would alleviate dextran sulfate sodium (DSS) induced colitis via modulating intestinal microbiota. The effect of RPT on mice gut microbiota was evaluated using 16S rRNA gene amplicon sequencing, broad-spectrum antibiotic (ABX) treatment, and fecal microbiota transplantation (FMT). Pretreatment with RPT enhanced intestinal barrier function, reduced colonic and serum proinflammatory cytokine and macrophage infiltration, and preserved the resilience of gut microbiota in mice during a DSS challenge. Administration of either RPT-regulated or healthy control-derived gut microbiota showed similar protection against colitis, and such protection could not be recapitulated with fecal microbiota from ABX-treated mice, suggesting a key role of protective consortium in the disease protection. Mechanistically, cecal contents of short-chain fatty acids (SCFAs) and colonic peroxisome proliferator activated receptor-γ (PPAR-γ) expression in colitis mice increased significantly by RPT intervention. Collectively, RPT treatment improved DSS-induced colitis by partially reversing the dysbiosis state of gut microbiota, which might be associated with an increase in SCFA level and PPAR-γ expression.}, }
@article {pmid33569665, year = {2021}, author = {Wada, A and Higashiyama, M and Kurihara, C and Ito, S and Tanemoto, R and Mizoguchi, A and Nishii, S and Inaba, K and Sugihara, N and Hanawa, Y and Horiuchi, K and Shibuya, N and Akiyama, M and Okada, Y and Watanabe, C and Komoto, S and Tomita, K and Takei, F and Hokari, R}, title = {Protective Effect of Luminal Uric Acid Against Indomethacin-Induced Enteropathy: Role of Antioxidant Effect and Gut Microbiota.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, pmid = {33569665}, issn = {1573-2568}, abstract = {BACKGROUND: Uric acid (UA) has anti- and pro-inflammatory properties. We previously revealed that elevated serum UA levels provide protection against murine small intestinal injury probably via luminal UA secreted in the small intestine. Luminal UA may act as an antioxidant, preventing microbiota vulnerability to oxidative stress. However, whether luminal UA is increased under hyperuricemia and plays a protective role in a dose-dependent manner as well as the mechanism by which luminal UA exerts its protective effects on enteropathy remains unknown.<br><br>METHODS: Inosinic acid (IMP) (1000 mg/kg, i.p.) was administered to obtain high serum UA (HUA) and moderate serum UA (500 mg/kg IMP, i.p.) mice. UA concentrations and levels of oxidative stress markers in the serum and intestine were measured. Mice received indomethacin (20 mg/kg, i.p.) to evaluate the effects of UA on indomethacin-induced enteropathy. Reactive oxygen species (ROS) on the ileal mucosa were analyzed. The fecal microbiota of HUA mice was transplanted to investigate its effect on indomethacin-induced enteropathy.<br><br>RESULTS: IMP increased luminal UA dose-dependently, with higher levels of luminal antioxidant markers. Indomethacin-induced enteropathy was significantly ameliorated in both UA-elevated groups, with decreased indomethacin-induced luminal ROS. The microbiota of HUA mice showed a significant increase in α-diversity and a significant difference in β-diversity from the control. Fecal microbiota transplantation from HUA mice ameliorated indomethacin-induced enteropathy.<br><br>CONCLUSIONS: The protective role of luminal UA in intestinal injury is likely exerted via oxidative stress elimination and microbiota composition modulation, preferably for gut immunity. Therefore, enhancing anaerobic conditions using antioxidants is a potential therapeutic target.}, }
@article {pmid33567176, year = {2021}, author = {Janket, SJ and Conte, HA and Diamandis, EP}, title = {Inappropriate extrapolations abound in fecal microbiota research.}, journal = {Clinical chemistry and laboratory medicine}, volume = {59}, number = {7}, pages = {e307-e308}, doi = {10.1515/cclm-2020-1862}, pmid = {33567176}, issn = {1437-4331}, }
@article {pmid33564705, year = {2020}, author = {Gouveia, C and Palos, C and Pereira, P and Roque Ramos, L and Cravo, M}, title = {Fecal Microbiota Transplant in a Patient Infected with Multidrug-Resistant Bacteria: A Case Report.}, journal = {GE Portuguese journal of gastroenterology}, volume = {28}, number = {1}, pages = {56-61}, pmid = {33564705}, issn = {2341-4545}, abstract = {Introduction: There has been a growing interest in fecal microbiota transplantation (FMT) as a way to manipulate gut microbiota, with potential benefit in patients infected with multidrug-resistant (MDR) bacteria.<br><br>Case Presentation: We present the case of an 87-year-old male with recurrent ascending cholangitis due to biliary atony and impaired biliary drainage after multiple biliary sphincterotomies and two papillary balloon dilations. In this context, a choledochoduodenostomy was performed, but the patient kept on having repeated episodes of acute cholangitis, resulting in multiple hospitalizations, every other week, with need of multiple broad-spectrum antibiotic courses, which led to bacteremias with MDR microorganisms. Several therapeutic strategies such as prophylactic antibiotics (including rifaximin), pre- and probiotics, prokinetics, and ursodeoxycholic acid were unsuccessfully attempted. After multidisciplinary case discussion, an FMT was proposed, with the aim of manipulating gut microbiota and decreasing MDR bacteremias. We first performed FMT via colonoscopy in September 2018, after which the patient still had 3 more hospitalizations for acute cholangitis, but isolated bacteria in blood cultures were resistant only to amoxicillin and clavulanic acid. Considering this apparent change in the microbial resistance profile, we performed a second FMT in January 2019 via the upper gastrointestinal route. During the next 4 months, the patient remained well. In April 2019, the patient relapsed again with three more episodes of cholangitis, for which we repeated the FMT via upper gastrointestinal endoscopy. No readmissions were observed during the next 4 months. All three FMTs were performed without complications.<br><br>Discussion and Conclusion: FMT seems to be a safe procedure and was effective in decreasing hospital admissions and changing the profile of MDR bacteria previously isolated from blood cultures.}, }
@article {pmid33561650, year = {2021}, author = {Huang, W and Kong, D}, title = {The intestinal microbiota as a therapeutic target in the treatment of NAFLD and ALD.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {135}, number = {}, pages = {111235}, doi = {10.1016/j.biopha.2021.111235}, pmid = {33561650}, issn = {1950-6007}, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Bacteria/drug effects/*metabolism ; Diet, Healthy ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Humans ; Intestines/*microbiology ; Liver/*metabolism/pathology ; Liver Diseases, Alcoholic/metabolism/*microbiology/pathology/therapy ; Non-alcoholic Fatty Liver Disease/metabolism/*microbiology/pathology/therapy ; Prebiotics ; Probiotics/therapeutic use ; }, abstract = {INTRODUCTION: Liver diseases are currently common disorders worldwide. Especially, the proportion of patients with nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) is growing globally. An increasing number of studies have revealed a close relationship between the intestinal microbiota and the development of NAFLD and ALD. A better understanding of the role of intestinal microbiota and the intestine-liver axis thus might lead to the development novel therapies for the treatment of these diseases.}, }
@article {pmid33558654, year = {2021}, author = {Zhang, JD and Liu, J and Zhu, SW and Fang, Y and Wang, B and Jia, Q and Hao, HF and Kao, JY and He, QH and Song, LJ and Liu, F and Zhu, BL and Owyang, C and Duan, LP}, title = {Berberine alleviates visceral hypersensitivity in rats by altering gut microbiome and suppressing spinal microglial activation.}, journal = {Acta pharmacologica Sinica}, volume = {}, number = {}, pages = {}, pmid = {33558654}, issn = {1745-7254}, abstract = {Accumulating evidence shows that agents targeting gut dysbiosis are effective for improving symptoms of irritable bowel syndrome (IBS). However, the potential mechanisms remain unclear. In this study we investigated the effects of berberine on the microbiota-gut-brain axis in two rat models of visceral hypersensitivity, i.e., specific pathogen-free SD rats subjected to chronic water avoidance stress (WAS) and treated with berberine (200 mg· kg-1 ·d-1, ig, for 10 days) as well as germ-free (GF) rats subjected to fecal microbiota transplantation (FMT) from a patient with IBS (designated IBS-FMT) and treated with berberine (200 mg· kg-1 ·d-1, ig, for 2 weeks). Before the rats were sacrificed, visceral sensation and depressive behaviors were evaluated. Then colonic tryptase was measured and microglial activation in the dorsal lumbar spinal cord was assessed. The fecal microbiota was profiled using 16S rRNA sequencing, and short chain fatty acids (SCFAs) were measured. We showed that berberine treatment significantly alleviated chronic WAS-induced visceral hypersensitivity and activation of colonic mast cells and microglia in the dorsal lumbar spinal cord. Transfer of fecal samples from berberine-treated stressed donors to GF rats protected against acute WAS. FMT from a patient with IBS induced visceral hypersensitivity and pro-inflammatory phenotype in microglia, while berberine treatment reversed the microglial activation and altered microbial composition and function and SCFA profiles in stools of IBS-FMT rats. We demonstrated that berberine did not directly influence LPS-induced microglial activation in vitro. In both models, several SCFA-producing genera were enriched by berberine treatment, and positively correlated to the morphological parameters of microglia. In conclusion, activation of microglia in the dorsal lumbar spinal cord was involved in the pathogenesis of IBS caused by dysregulation of the microbiota-gut-brain axis, and the berberine-altered gut microbiome mediated the modulatory effects of the agent on microglial activation and visceral hypersensitivity, providing a potential option for the treatment of IBS.}, }
@article {pmid33557941, year = {2021}, author = {Liu, F and Ye, S and Zhu, X and He, X and Wang, S and Li, Y and Lin, J and Wang, J and Lin, Y and Ren, X and Li, Y and Deng, Z}, title = {Gastrointestinal disturbance and effect of fecal microbiota transplantation in discharged COVID-19 patients.}, journal = {Journal of medical case reports}, volume = {15}, number = {1}, pages = {60}, pmid = {33557941}, issn = {1752-1947}, support = {81970156//National Natural Science foundation of China/ ; 81970118//National Natural Science foundation of China/ ; }, mesh = {Aged ; *B-Lymphocyte Subsets ; Bacteroidetes ; Bifidobacterium ; COVID-19/*complications/immunology ; Dysbiosis/microbiology/*therapy ; Faecalibacterium ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Diseases/microbiology/*therapy ; *Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Patient Discharge ; Proteobacteria ; SARS-CoV-2 ; Young Adult ; }, abstract = {BACKGROUND: To investigate the potential beneficial effect of fecal microbiota transplantation (FMT) on gastrointestinal symptoms, gut dysbiosis and immune status in discharged COVID-19 patients.<br><br>CASE PRESENTATION: A total of 11 COVID-19 patients were recruited in April, 2020, about one month on average after they were discharged from the hospital. All subjects received FMT for 4 consecutive days by oral capsule administrations with 10 capsules for each day. In total, 5 out of 11 patients reported to be suffered from gastrointestinal symptoms, which were improved after FMT. After FMT, alterations of B cells were observed, which was characterized as decreased naive B cell (P = 0.012) and increased memory B cells (P = 0.001) and non-switched B cells (P = 0.012).The microbial community richness indicated by operational taxonomic units number, observed species and Chao1 estimator was marginally increased after FMT. Gut microbiome composition of discharged COVID-19 patients differed from that of the general population at both phylum and genera level, which was characterized with a lower proportion of Firmicutes (41.0%) and Actinobacteria (4.0%), higher proportion of Bacteroidetes (42.9%) and Proteobacteria (9.2%). FMT can partially restore the gut dysbiosis by increasing the relative abundance of Actinobacteria (15.0%) and reducing Proteobacteria (2.8%) at the phylum level. At the genera level, Bifidobacterium and Faecalibacterium had significantly increased after FMT.<br><br>CONCLUSIONS: After FMT, altered peripheral lymphocyte subset, restored gut microbiota and alleviated gastrointestinal disorders were observe, suggesting that FMT may serve as a potential therapeutic and rehabilitative intervention for the COVID-19.}, }
@article {pmid33557125, year = {2021}, author = {Pession, A and Zama, D and Muratore, E and Leardini, D and Gori, D and Guaraldi, F and Prete, A and Turroni, S and Brigidi, P and Masetti, R}, title = {Fecal Microbiota Transplantation in Allogeneic Hematopoietic Stem Cell Transplantation Recipients: A Systematic Review.}, journal = {Journal of personalized medicine}, volume = {11}, number = {2}, pages = {}, pmid = {33557125}, issn = {2075-4426}, support = {GR-2013-02357136//Ministero della Salute/ ; }, abstract = {The disruption of gut microbiota eubiosis has been linked to major complications in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Various strategies have been developed to reduce dysbiosis and related complications. Fecal microbiota transplantation (FMT) consists of the infusion of fecal matter from a healthy donor to restore impaired intestinal homeostasis, and could be applied in the allo-HSCT setting. We conducted a systematic review of studies addressing the use of FMT in allo-HSCT patients. In the 23 papers included in the qualitative synthesis, FMT was used for the treatment of recurrent Clostridioides difficile infections or as a therapeutic strategy for steroid-resistant gut aGvHD. FMT was also performed with a preventive aim (e.g., to decolonize from antibiotic-resistant bacteria). Additional knowledge on the biological mechanisms underlying clinical findings is needed in order to employ FMT in clinical practice. There is also concern regarding the administration of microbial consortia in immune-compromised patients with altered gut permeability. Therefore, the safety profile and efficacy of the procedure must be determined to better assess the role of FMT in allo-HSCT recipients.}, }
@article {pmid33556916, year = {2021}, author = {Wu, L and Yan, Q and Chen, F and Cao, C and Wang, S}, title = {Bupleuri radix extract ameliorates impaired lipid metabolism in high-fat diet-induced obese mice via gut microbia-mediated regulation of FGF21 signaling pathway.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {135}, number = {}, pages = {111187}, doi = {10.1016/j.biopha.2020.111187}, pmid = {33556916}, issn = {1950-6007}, mesh = {Adipose Tissue, White/*drug effects/metabolism ; Animals ; Anti-Obesity Agents/isolation &amp; purification/*pharmacology ; Bacteria/growth &amp; development/*metabolism ; *Bupleurum/chemistry ; Diet, High-Fat ; Disease Models, Animal ; Fibroblast Growth Factors/*metabolism ; *Gastrointestinal Microbiome ; Intestines/*microbiology ; Lipid Metabolism/*drug effects ; Liver/*drug effects/metabolism ; Male ; Mice, Inbred C57BL ; Obesity/*drug therapy/metabolism/microbiology ; Plant Extracts/isolation &amp; purification/*pharmacology ; Plant Roots ; Signal Transduction ; }, abstract = {BACKGROUND: Obesity and its comorbidities are associated with abnormal lipid metabolism and gut microbiota dysbiosis. Bupleuri Radix is a medicinal plant used in traditional Chinese medicine with the prevention and treatment of obesity-related diseases. In this study, we aim to validate the regulation of Bupleuri Radix Extract (BupE) on lipid metabolism in obese mice, and try to find out the potential active components and reveal the underlying mechanisms.<br><br>METHODS: Ingredients in BupE, their circulating metabolites in mice and fecal biotransformation products were analyzed by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS). Western blotting, RT-PCR and ELISA were used for tests of objective genes and proteins. 16 s rRNA sequencing was performed to examine intestinal bacteria composition and microbes' functional changes were predicted with PICRUSt software. An absolute quantification method was set up via the construction of recombinant plasmid for the assays of intestinal flora. Specific microbial strains were cultured in anaerobic conditions and oral administrated to mice for intestinal mono-colonization.<br><br>RESULTS: BupE attenuated obesity, liver steatosis, and dyslipidemia in HFD-fed mice by up-regulating the expression of FGF21 in liver and white adipose tissue (WAT) as well as the downstream proteins of FGF21 signal pathway including β-klotho, GLUT1 and PGC-1α, etc. UPLC/Q-TOF-MS fingerprints showed no compounds from BupE or their metabolites or biotransformation products were detected in rodent serum samples. High-throughput pyrosequencing data indicated that BupE reversed obesity-induced constructional and functional alterations of intestinal flora. Two bacterial strains, Bacteroides acidifaciens (B. acidifaciens) and Ruminococcus gnavus (R. gnavus), were separated and identified from the feces of obese mice and by intestinal mono-colonization they were verified to intervene in the anti-obesity effects of BupE on mice.<br><br>CONCLUSION: These data suggest that BupE protects against diet-induced obesity and counteracts metabolic syndrome features consistent with a mechanism involving the gut-liver axis that boosts hepatic FGF21 secretion and consequent down-stream proteins expression relating to lipid metabolism. And in this gut-liver axis, intestinal microbes such as B.acidifaciens and R.gnavus play an indispensable role.}, }
@article {pmid33556154, year = {2021}, author = {Jung, HJ and Sorbara, MT and Pamer, EG}, title = {TAM mediates adaptation of carbapenem-resistant Klebsiella pneumoniae to antimicrobial stress during host colonization and infection.}, journal = {PLoS pathogens}, volume = {17}, number = {2}, pages = {e1009309}, pmid = {33556154}, issn = {1553-7374}, support = {P41 GM108569/GM/NIGMS NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; P30 CA060553/CA/NCI NIH HHS/United States ; S10 OD025194/OD/NIH HHS/United States ; R01 AI042135/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 AI095706/AI/NIAID NIH HHS/United States ; }, mesh = {*Adaptation, Physiological ; Animals ; Anti-Bacterial Agents/*pharmacology ; Bacterial Outer Membrane Proteins/genetics/*metabolism ; Carbapenem-Resistant Enterobacteriaceae/*drug effects ; Carbapenems/pharmacology ; Cell Membrane Permeability ; Female ; Klebsiella Infections/*drug therapy/genetics/metabolism/microbiology ; Klebsiella pneumoniae/*drug effects ; Mice ; Mice, Inbred C57BL ; Proteome/*metabolism ; Stress, Physiological ; }, abstract = {Gram-negative pathogens, such as Klebsiella pneumoniae, remodel their outer membrane (OM) in response to stress to maintain its integrity as an effective barrier and thus to promote their survival in the host. The emergence of carbapenem-resistant K. pneumoniae (CR-Kp) strains that are resistant to virtually all antibiotics is an increasing clinical problem and OM impermeability has limited development of antimicrobial agents because higher molecular weight antibiotics cannot access sites of activity. Here, we demonstrate that TAM (translocation and assembly module) deletion increases CR-Kp OM permeability under stress conditions and enhances sensitivity to high-molecular weight antimicrobials. SILAC-based proteomic analyses revealed mis-localization of membrane proteins in the TAM deficient strain. Stress-induced sensitization enhances clearance of TAM-deficient CR-Kp from the gut lumen following fecal microbiota transplantation and from infection sites following pulmonary or systemic infection. Our study suggests that TAM, as a regulator of OM permeability, represents a potential target for development of agents that enhance the effectiveness of existing antibiotics.}, }
@article {pmid33554953, year = {2021}, author = {Sofi, MH and Wu, Y and Ticer, T and Schutt, S and Bastian, D and Choi, HJ and Tian, L and Mealer, C and Liu, C and Westwater, C and Armeson, KE and Alekseyenko, AV and Yu, XZ}, title = {A single strain of Bacteroides fragilis protects gut integrity and reduces GVHD.}, journal = {JCI insight}, volume = {6}, number = {3}, pages = {}, pmid = {33554953}, issn = {2379-3708}, support = {R01 AI135631/AI/NIAID NIH HHS/United States ; U54 CA210962/CA/NCI NIH HHS/United States ; R01 HL140953/HL/NHLBI NIH HHS/United States ; R01 LM012517/LM/NLM NIH HHS/United States ; R01 HL137373/HL/NHLBI NIH HHS/United States ; P30 DK123704/DK/NIDDK NIH HHS/United States ; R01 AI118305/AI/NIAID NIH HHS/United States ; }, mesh = {Allografts ; Animals ; Bacteroides fragilis/*immunology ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology ; Graft vs Host Disease/immunology/microbiology/*prevention &amp; control ; Graft vs Leukemia Effect/immunology ; Hematopoietic Stem Cell Transplantation/adverse effects ; Isoantigens/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Inbred DBA ; T-Lymphocytes/immunology ; Tumor Cells, Cultured ; }, abstract = {Graft-versus-host disease (GVHD) is a pathological process caused by an exaggerated donor lymphocyte response to host antigens after allogeneic hematopoietic cell transplantation (allo-HCT). Donor T cells undergo extensive clonal expansion and differentiation, which culminate in damage to recipient target organs. Damage to the gastrointestinal tract is a main contributor to morbidity and mortality. The loss of diversity among intestinal bacteria caused by pretransplant conditioning regimens leads to an outgrowth of opportunistic pathogens and exacerbated GVHD after allo-HCT. Using murine models of allo-HCT, we found that an increase of Bacteroides in the intestinal microbiota of the recipients was associated with reduced GVHD in mice given fecal microbial transplantation. Administration of Bacteroides fragilis through oral gavage increased gut microbiota diversity and beneficial commensal bacteria and significantly ameliorated acute and chronic GVHD development. Preservation of gut integrity following B. fragilis exposure was likely attributed to increased short chain fatty acids, IL-22, and regulatory T cells, which in turn improved gut tight junction integrity and reduced inflammatory cytokine production of pathogenic T cells. The current study provides a proof of concept that a single strain of commensal bacteria can be a safe and effective means to protect gut integrity and ameliorate GVHD after allo-HCT.}, }
@article {pmid33554105, year = {2021}, author = {Jeevarathinam, AS and Guo, F and Williams, T and Smolen, JA and Hyde, JA and McShane, MJ and de Figueiredo, P and Alge, DL}, title = {Enzyme functionalized microgels enable precise regulation of dissolved oxygen and anaerobe culture.}, journal = {Materials today. Bio}, volume = {9}, number = {}, pages = {100092}, pmid = {33554105}, issn = {2590-0064}, abstract = {Anaerobes are a major constituent of the gut microbiome and profoundly influence the overall health of humans. However, the lack of a simple, cost-effective, and scalable system that mimics the anaerobic conditions of the human gut is hindering research on the gut microbiome and the development of therapeutics. Here, we address this gap by using glucose oxidase and catalase containing gelatin microparticles (GOx-CAT-GMPs) to precisely regulate dissolved oxygen concentration [O2] via GOx-mediated consumption of oxygen. Fluorescence images generated using conjugated polymer afterglow nanoparticles showed that [O2] can be tuned from 257.9 ​± ​6.2 to 0.0 ​± ​4.0 ​μM using GOx-CAT-GMPs. Moreover, when the obligate anaerobe Bacteroides thetaiotaomicron was inoculated in media containing GOx-CAT-GMPs, bacterial growth under ambient oxygen was comparable to control conditions in an anaerobic chamber (5.4 ​× ​105 and 8.8 ​× ​105 colony forming units mL-1, respectively). Finally, incorporating GOx-CAT-GMPs into a bioreactor that permitted continuous radial diffusion of oxygen and glucose generated a gut-mimetic [O2] gradient of 132.4 ​± ​2.6 ​μM in the outer ring of the reactor to 7.9 ​± ​1.7 ​μM at the core. Collectively, these results indicate that GOx-CAT-GMPs are highly effective oxygen-regulating materials. These materials can potentially be leveraged to advance gut microbiome research and fecal microbiota transplantation, particularly in low-resource settings.}, }
@article {pmid33553973, year = {2021}, author = {Bajaj, JS and Shamsaddini, A and Fagan, A and Sterling, RK and Gavis, E and Khoruts, A and Fuchs, M and Lee, H and Sikaroodi, M and Gillevet, PM}, title = {Fecal Microbiota Transplant in Cirrhosis Reduces Gut Microbial Antibiotic Resistance Genes: Analysis of Two Trials.}, journal = {Hepatology communications}, volume = {5}, number = {2}, pages = {258-271}, pmid = {33553973}, issn = {2471-254X}, abstract = {Antibiotic resistance leads to poor outcomes in cirrhosis. Fecal microbiota transplant (FMT) is associated with reduction in antibiotic resistance gene (ARG) burden in patients without cirrhosis; however, the impact in cirrhosis is unclear. We aimed to study the effect of capsule and enema FMT on ARG abundance in fecal samples, which were collected during two published FMT trials in patients with cirrhosis on rifaximin, lactulose, and proton pump inhibitors. ARGs were identified using metagenomics and mapped against the Comprehensive Antibiotic Resistance Database. Changes in ARG abundance were studied within/between groups. The capsule FMT trial involved a one-time FMT or placebo capsule administration with stool collection at baseline and week 4 postintervention. Antibiotics+enema FMT included preprocedure antibiotics followed by FMT enema versus standard-of-care (SOC). Stool was collected at baseline, postantibiotics, and day 7/15 postintervention. Both trials included 20 patients each. There was no safety/infection signal linked to FMT. In the capsule trial, beta-lactamase (OXY/LEN) expression decreased post-FMT versus baseline. Compared to placebo, patients who were post-FMT had lower abundance of vancomycin (VanH), beta-lactamase (ACT), and rifamycin ARGs; the latter was associated with cognitive improvement. No changes were seen within patients treated with placebo. In the antibiotics+enema trial for postantibiotics at day 7 versus baseline, there was an increase in vancomycin and beta-lactamase ARGs, which decreased at day 15. However, quinolone resistance increased at day 15 versus baseline. Between SOC and FMT, day 7 had largely lower ARG (CfxA beta-lactamase, VanW, and VanX) that continued at day 15 (cepA beta-lactamase, VanW). No changes were seen within the SOC group. Conclusion: Despite differences in routes of administration and preintervention antibiotics, we found that ARG abundance is largely reduced after FMT compared to pre-FMT baseline and non-FMT groups in decompensated cirrhosis.}, }
@article {pmid33553045, year = {2020}, author = {Mohammadi, SO and Yadegar, A and Kargar, M and Mirjalali, H and Kafilzadeh, F}, title = {The impact of Helicobacter pylori infection on gut microbiota-endocrine system axis; modulation of metabolic hormone levels and energy homeostasis.}, journal = {Journal of diabetes and metabolic disorders}, volume = {19}, number = {2}, pages = {1855-1861}, pmid = {33553045}, issn = {2251-6581}, abstract = {The gut microbiota is a complex ecosystem that is involved in the development and preservation of the immune system, energy homeostasis and nutritional status of the host. The crosstalk between gut microbiota and the host cells modulates host physiology and metabolism through different mechanisms. Helicobacter pylori (H. pylori) is known to reside in the gastric mucosa, induce inflammation, and alter both gastric and intestinal microbiota resulting in a broad spectrum of diseases, in particular metabolic syndrome-related disorders. Infection with H. pylori have been shown to affect production level and physiological regulation of the gut metabolic hormones such as ghrelin and leptin which are involved in food intake, energy expenditure and body mass. In this study, we reviewed and discussed data from the literature and follow-up investigations that links H. pylori infection to alterations of the gut microbiota and metabolic hormone levels, which can exert broad influences on host metabolism, energy homeostasis, behavior, appetite, growth, reproduction and immunity. Also, we discussed the strong potential of fecal microbiota transplantation (FMT) as an innovative and promising investigational treatment option for homeostasis of metabolic hormone levels to overcome H. pylori-associated metabolic syndrome-related disorders.}, }
@article {pmid33549144, year = {2021}, author = {Strati, F and Pujolassos, M and Burrello, C and Giuffrè, MR and Lattanzi, G and Caprioli, F and Troisi, J and Facciotti, F}, title = {Antibiotic-associated dysbiosis affects the ability of the gut microbiota to control intestinal inflammation upon fecal microbiota transplantation in experimental colitis models.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {39}, pmid = {33549144}, issn = {2049-2618}, mesh = {Animals ; Anti-Bacterial Agents/*adverse effects/pharmacology ; Colitis/*chemically induced/immunology/*microbiology/pathology ; *Disease Models, Animal ; Dysbiosis/chemically induced/*microbiology ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*drug effects/immunology ; Humans ; Male ; Metronidazole/pharmacology ; Mice ; Natural Killer T-Cells/drug effects/immunology ; Streptomycin/adverse effects ; Th1 Cells/drug effects/immunology ; Th17 Cells/drug effects/immunology ; Vancomycin/adverse effects ; }, abstract = {BACKGROUND: The gut microbiota plays a central role in host physiology and in several pathological mechanisms in humans. Antibiotics compromise the composition and functions of the gut microbiota inducing long-lasting detrimental effects on the host. Recent studies suggest that the efficacy of different clinical therapies depends on the action of the gut microbiota. Here, we investigated how different antibiotic treatments affect the ability of the gut microbiota to control intestinal inflammation upon fecal microbiota transplantation in an experimental colitis model and in ex vivo experiments with human intestinal biopsies.<br><br>RESULTS: Murine fecal donors were pre-treated with different antibiotics, i.e., vancomycin, streptomycin, and metronidazole before FMT administration to colitic animals. The analysis of the gut microbiome, fecal metabolome, and the immunophenotyping of colonic lamina propria immune cells revealed that antibiotic pre-treatment significantly influences the capability of the microbiota to control intestinal inflammation. Streptomycin and vancomycin-treated microbiota failed to control intestinal inflammation and were characterized by the blooming of pathobionts previously associated with IBD as well as with metabolites related to the presence of oxidative stress and metabolism of simple sugars. On the contrary, the metronidazole-treated microbiota retained its ability to control inflammation co-occurring with the enrichment of Lactobacillus and of innate immune responses involving iNKT cells. Furthermore, ex vivo cultures of human intestinal lamina propria mononuclear cells and iNKT cell clones from IBD patients with vancomycin pre-treated sterile fecal water showed a Th1/Th17 skewing in CD4+ T-cell populations; metronidazole, on the other hand, induced the polarization of iNKT cells toward the production of IL10.<br><br>CONCLUSIONS: Diverse antibiotic regimens affect the ability of the gut microbiota to control intestinal inflammation in experimental colitis by altering the microbial community structure and microbiota-derived metabolites. Video Abstract.}, }
@article {pmid33549047, year = {2021}, author = {Xu, F and Li, N and Wang, C and Xing, H and Chen, D and Wei, Y}, title = {Clinical efficacy of fecal microbiota transplantation for patients with small intestinal bacterial overgrowth: a randomized, placebo-controlled clinic study.}, journal = {BMC gastroenterology}, volume = {21}, number = {1}, pages = {54}, pmid = {33549047}, issn = {1471-230X}, mesh = {*Bacterial Infections ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Lactulose ; Treatment Outcome ; }, abstract = {BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is characterized by the condition that bacteria overgrowth in the small intestine. Fecal microbiota transplantation (FMT) has been applied as an effective tool for reestablishing the structure of gut microbiota. However, whether FMT could be applied as a routine SIBO treatment has not been investigated.<br><br>METHODS: In this trial, 55 SIBO patients were enrolled. All participants were randomized in two groups, and were given FMT capsule or placebo capsules once a week for 4 consecutive weeks. Measurements including the lactulose hydrogen breath test gastrointestinal symptoms, as well as fecal microbiota diversity were assessed before and after FMT therapy.<br><br>RESULTS: Gastrointestinal symptoms significantly improved in SIBO patients after treatment with FMT compared to participants in placebo group. The gut microbiota diversity of FMT group had a significant increase, while placebo group showed none.<br><br>CONCLUSIONS: This study suggests that applying FMT for patients with SIBO can alleviate gastrointestinal symptoms, indicating that FMT may be a promising and novel therapeutic regimen for SIBO. Trial registry This study was retrospectively registered with the Chinese Clinical Trial registry on 2019.7.10 (ID: ChiCTR1900024409, http://www.chictr.org.cn).}, }
@article {pmid33546192, year = {2021}, author = {Parker, KD and Maurya, AK and Ibrahim, H and Rao, S and Hove, PR and Kumar, D and Kant, R and Raina, B and Agarwal, R and Kuhn, KA and Raina, K and Ryan, EP}, title = {Dietary Rice Bran-Modified Human Gut Microbial Consortia Confers Protection against Colon Carcinogenesis Following Fecal Transfaunation.}, journal = {Biomedicines}, volume = {9}, number = {2}, pages = {}, pmid = {33546192}, issn = {2227-9059}, support = {5R01CA201112/NH/NIH HHS/United States ; }, abstract = {Rice bran, removed from whole grain rice for white rice milling, has demonstrated efficacy for the control and suppression of colitis and colon cancer in multiple animal models. Dietary rice bran intake was shown to modify human stool metabolites as a result of modifications to metabolism by gut microbiota. In this study, human stool microbiota from colorectal cancer (CRC) survivors that consumed rice bran daily was examined by fecal microbiota transplantation (FMT) for protection from azoxymethane and dextran sodium sulfate (AOM/DSS) induced colon carcinogenesis in germ-free mice. Mice transfaunated with rice bran-modified microbiota communities (RMC) harbored fewer neoplastic lesions in the colon and displayed distinct enrichment of Flavonifractor and Oscillibacter associated with colon health, and the depletion of Parabacteroides distasonis correlated with increased tumor burden. Two anti-cancer metabolites, myristoylcarnitine and palmitoylcarnitine were increased in the colon of RMC transplanted mice. Trimethylamine-N-oxide (TMAO) and tartarate that are implicated in CRC development were reduced in murine colon tissue after FMT with rice bran-modified human microbiota. Findings from this study show that rice bran modified gut microbiota from humans confers protection from colon carcinogenesis in mice and suggests integrated dietary-FMT intervention strategies should be tested for colorectal cancer control, treatment, and prevention.}, }
@article {pmid33546191, year = {2021}, author = {Plaza-Díaz, J and Solis-Urra, P and Aragón-Vela, J and Rodríguez-Rodríguez, F and Olivares-Arancibia, J and Álvarez-Mercado, AI}, title = {Insights into the Impact of Microbiota in the Treatment of NAFLD/NASH and Its Potential as a Biomarker for Prognosis and Diagnosis.}, journal = {Biomedicines}, volume = {9}, number = {2}, pages = {}, pmid = {33546191}, issn = {2227-9059}, abstract = {Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of chronic liver illness associated with obesity and metabolic disorders, such as hypertension, dyslipidemia, or type 2 diabetes mellitus. A more severe type of NAFLD, non-alcoholic steatohepatitis (NASH), is considered an ongoing global health threat and dramatically increases the risks of cirrhosis, liver failure, and hepatocellular carcinoma. Several reports have demonstrated that liver steatosis is associated with the elevation of certain clinical and biochemical markers but with low predictive potential. In addition, current imaging methods are inaccurate and inadequate for quantification of liver steatosis and do not distinguish clearly between the microvesicular and the macrovesicular types. On the other hand, an unhealthy status usually presents an altered gut microbiota, associated with the loss of its functions. Indeed, NAFLD pathophysiology has been linked to lower microbial diversity and a weakened intestinal barrier, exposing the host to bacterial components and stimulating pathways of immune defense and inflammation via toll-like receptor signaling. Moreover, this activation of inflammation in hepatocytes induces progression from simple steatosis to NASH. In the present review, we aim to: (a) summarize studies on both human and animals addressed to determine the impact of alterations in gut microbiota in NASH; (b) evaluate the potential role of such alterations as biomarkers for prognosis and diagnosis of this disorder; and (c) discuss the involvement of microbiota in the current treatment for NAFLD/NASH (i.e., bariatric surgery, physical exercise and lifestyle, diet, probiotics and prebiotics, and fecal microbiota transplantation).}, }
@article {pmid33545935, year = {2021}, author = {Choi, E and Lee, SJ and Lee, S and Yi, J and Lee, YS and Chang, SY and Jeong, HY and Joo, Y}, title = {Comprehensive, multisystem, mechanical decolonization of Vancomycin-Resistant Enterococcus and Carbapenem-Resistant Enterobacteriacease without the use of antibiotics.}, journal = {Medicine}, volume = {100}, number = {3}, pages = {e23686}, pmid = {33545935}, issn = {1536-5964}, mesh = {Aged ; Bedding and Linens/microbiology ; Carbapenem-Resistant Enterobacteriaceae/*isolation &amp; purification ; Chlorhexidine/administration &amp; dosage ; Clinical Protocols ; Clothing ; Cross Infection/microbiology/*therapy/transmission ; Enema/methods ; Enterobacteriaceae Infections/microbiology/*therapy/transmission ; Environmental Microbiology ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; Humans ; Hygiene ; Infection Control/*methods ; Lactobacillus/metabolism ; Male ; Middle Aged ; Prospective Studies ; Quarantine ; Skin/microbiology ; Treatment Outcome ; Vancomycin-Resistant Enterococci/*isolation &amp; purification ; }, }
@article {pmid33542131, year = {2021}, author = {Davar, D and Dzutsev, AK and McCulloch, JA and Rodrigues, RR and Chauvin, JM and Morrison, RM and Deblasio, RN and Menna, C and Ding, Q and Pagliano, O and Zidi, B and Zhang, S and Badger, JH and Vetizou, M and Cole, AM and Fernandes, MR and Prescott, S and Costa, RGF and Balaji, AK and Morgun, A and Vujkovic-Cvijin, I and Wang, H and Borhani, AA and Schwartz, MB and Dubner, HM and Ernst, SJ and Rose, A and Najjar, YG and Belkaid, Y and Kirkwood, JM and Trinchieri, G and Zarour, HM}, title = {Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients.}, journal = {Science (New York, N.Y.)}, volume = {371}, number = {6529}, pages = {595-602}, pmid = {33542131}, issn = {1095-9203}, support = {P30 CA047904/CA/NCI NIH HHS/United States ; R01 CA222203/CA/NCI NIH HHS/United States ; R01 CA228181/CA/NCI NIH HHS/United States ; }, mesh = {Antibodies, Monoclonal, Humanized/*therapeutic use ; Antineoplastic Agents, Immunological/*therapeutic use ; CD8-Positive T-Lymphocytes/immunology ; *Drug Resistance, Neoplasm ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Interleukin-8/immunology ; Lymphocyte Activation ; Lymphocytes, Tumor-Infiltrating/immunology ; Melanoma/*therapy ; Myeloid Cells/immunology ; Programmed Cell Death 1 Receptor/*antagonists &amp; inhibitors ; Skin Neoplasms/*therapy ; Tumor Microenvironment/immunology ; }, abstract = {Anti-programmed cell death protein 1 (PD-1) therapy provides long-term clinical benefits to patients with advanced melanoma. The composition of the gut microbiota correlates with anti-PD-1 efficacy in preclinical models and cancer patients. To investigate whether resistance to anti-PD-1 can be overcome by changing the gut microbiota, this clinical trial evaluated the safety and efficacy of responder-derived fecal microbiota transplantation (FMT) together with anti-PD-1 in patients with PD-1-refractory melanoma. This combination was well tolerated, provided clinical benefit in 6 of 15 patients, and induced rapid and durable microbiota perturbation. Responders exhibited increased abundance of taxa that were previously shown to be associated with response to anti-PD-1, increased CD8+ T cell activation, and decreased frequency of interleukin-8-expressing myeloid cells. Responders had distinct proteomic and metabolomic signatures, and transkingdom network analyses confirmed that the gut microbiome regulated these changes. Collectively, our findings show that FMT and anti-PD-1 changed the gut microbiome and reprogrammed the tumor microenvironment to overcome resistance to anti-PD-1 in a subset of PD-1 advanced melanoma.}, }
@article {pmid33542126, year = {2021}, author = {Woelk, CH and Snyder, A}, title = {Modulating gut microbiota to treat cancer.}, journal = {Science (New York, N.Y.)}, volume = {371}, number = {6529}, pages = {573-574}, doi = {10.1126/science.abg2904}, pmid = {33542126}, issn = {1095-9203}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Immunotherapy ; *Melanoma ; *Microbiota ; }, }
@article {pmid33537709, year = {2021}, author = {Kim, M and Huda, MN and Bennett, BJ}, title = {Sequence Meets Function-Microbiota And Cardiovascular Disease.}, journal = {Cardiovascular research}, volume = {}, number = {}, pages = {}, doi = {10.1093/cvr/cvab030}, pmid = {33537709}, issn = {1755-3245}, support = {R01 HL128572/HL/NHLBI NIH HHS/United States ; }, abstract = {The discovery that gut-microbiota plays a profound role in human health has opened a new avenues of basic and clinical research. Application of ecological approaches where the Bacterial 16S rRNA gene is queried has provided a number of candidate bacteria associated with coronary artery disease and hypertension. We examine the associations between gut microbiota and a variety of CVD including atherosclerosis, coronary artery disease and blood pressure. These approaches are associative in nature and there is now increasing interest in identifying the mechanisms underlying these associations. We discuss three potential mechanisms including: gut permeability and endotoxemia, increased immune system activation, and microbial derived metabolites. In addition to discussing these potential mechanisms we highlight current studies manipulating the gut microbiota or microbial metabolites to move beyond sequenced based association studies. The goal of these mechanistic studies is to determine the mode of action by which the gut microbiota may affect disease susceptibility and severity. Importantly, the gut microbiota appears to have a significant effect on host metabolism and CVD by producing metabolites entering the host circulatory system such as short chain fatty acids (SCFAs) and trimethylamine N-Oxide (TMAO). Therefore, the intersection of metabolomics and microbiota research may yield novel targets to reduce disease susceptibility. Finally, we discuss approaches to demonstrate causality such as specific diet changes, inhibition of microbial pathways and fecal microbiota transplant.}, }
@article {pmid33537028, year = {2020}, author = {Gill, T and Rosenbaum, JT}, title = {Putative Pathobionts in HLA-B27-Associated Spondyloarthropathy.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {586494}, pmid = {33537028}, issn = {1664-3224}, support = {R01 EY029266/EY/NEI NIH HHS/United States ; P30 EY010572/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Gastrointestinal Microbiome/*immunology ; HLA-B27 Antigen/*genetics ; Humans ; Spondylarthropathies/*genetics/*immunology/*microbiology ; }, abstract = {Spondyloarthritis (SpA) is a group of immune mediated inflammatory diseases with a strong association to the major histocompatibility (MHC) class I molecule, HLA-B27. Although the association between HLA-B27 and AS has been known for almost 50 years, the mechanisms underlying disease pathogenesis are elusive. Over the years, three hypotheses have been proposed to explain HLA-B27 and disease association: 1) HLA B27 presents arthritogenic peptides and thus creates a pathological immune response; 2) HLA-B27 misfolding causes endoplasmic reticulum (ER) stress which activates the unfolded protein response (UPR); 3) HLA-B27 dimerizes on the cell surface and acts as a target for natural killer (NK) cells. None of these hypotheses explains SpA pathogenesis completely. Evidence supports the hypothesis that HLA-B27-related diseases have a microbial pathogenesis. In animal models of various SpAs, a germ-free environment abrogates disease development and colonizing these animals with gut commensal microbes can restore disease manifestations. The depth of microbial influence on SpA development has been realized due to our ability to characterize microbial communities in the gut using next-generation sequencing approaches. In this review, we will discuss various putative pathobionts in the pathogenesis of HLA-B27-associated diseases. We pursue whether a single pathobiont or a disruption of microbial community and function is associated with HLA-B27-related diseases. Furthermore, rather than a specific pathobiont, metabolic functions of various disease-associated microbes might be key. While the use of germ-free models of SpA have facilitated understanding the role of microbes in disease development, future studies with animal models that mimic diverse microbial communities instead of mono-colonization are indispensable. We discuss the causal mechanisms underlying disease pathogenesis including the role of these pathobionts on mucin degradation, mucosal adherence, and gut epithelial barrier disruption and inflammation. Finally, we review the various uses of microbes as therapeutic modalities including pre/probiotics, diet, microbial metabolites and fecal microbiota transplant. Unravelling these complex host-microbe interactions will lead to the development of new targets/therapies for alleviation of SpA and other HLA-B27 associated diseases.}, }
@article {pmid33536363, year = {2021}, author = {Seo, HS and Chin, HS and Kim, YH and Moon, HS and Kim, K and Nguyen, LP and Yong, D}, title = {Laboratory Aspects of Donor Screening for Fecal Microbiota Transplantation at a Korean Fecal Microbiota Bank.}, journal = {Annals of laboratory medicine}, volume = {41}, number = {4}, pages = {424-428}, pmid = {33536363}, issn = {2234-3814}, abstract = {Fecal microbiota transplantation (FMT) is a widely accepted alternative therapy for Clostridioides difficile infection and other gastrointestinal disorders. Thorough donor screening is required as a safety control measure to minimize transmission of infectious agents in FMT. We report the donor screening process and outcomes at a fecal microbiota bank in Korea. From August 2017 to June 2020, the qualification of 62 individuals as FMT donors was evaluated using clinical assessment and laboratory tests. Forty-six (74%) candidates were excluded after clinical assessment; high body mass index (>25) was the most common reason for exclusion, followed by atopy, asthma, and allergy history. Four of the remaining 16 (25%) candidates failed to meet laboratory test criteria, resulting in a 19% qualification rate. FMT donor re-qualification was conducted monthly as an additional safety control measure, and only three (5%) candidates were eligible for repeated donation. As high prevalence of multidrug-resistant organisms (55%) and Helicobacter pylori (44%) were detected in qualified donors during the screening, a urea breath test was added to the existing protocol. The present results emphasize the importance of implementing a donor re-qualification system to minimize risk factors not identified during initial donor screening.}, }
@article {pmid33535557, year = {2021}, author = {Parisi, A and Porzio, G and Pulcini, F and Cannita, K and Ficorella, C and Mattei, V and Delle Monache, S}, title = {What Is Known about Theragnostic Strategies in Colorectal Cancer.}, journal = {Biomedicines}, volume = {9}, number = {2}, pages = {}, pmid = {33535557}, issn = {2227-9059}, abstract = {Despite the paradigmatic shift occurred in recent years for defined molecular subtypes in the metastatic setting treatment, colorectal cancer (CRC) still remains an incurable disease in most of the cases. Therefore, there is an urgent need for new tools and biomarkers for both early tumor diagnosis and to improve personalized treatment. Thus, liquid biopsy has emerged as a minimally invasive tool that is capable of detecting genomic alterations from primary or metastatic tumors, allowing the prognostic stratification of patients, the detection of the minimal residual disease after surgical or systemic treatments, the monitoring of therapeutic response, and the development of resistance, establishing an opportunity for early intervention before imaging detection or worsening of clinical symptoms. On the other hand, preclinical and clinical evidence demonstrated the role of gut microbiota dysbiosis in promoting inflammatory responses and cancer initiation. Altered gut microbiota is associated with resistance to chemo drugs and immune checkpoint inhibitors, whereas the use of microbe-targeted therapies including antibiotics, pre-probiotics, and fecal microbiota transplantation can restore response to anticancer drugs, promote immune response, and therefore support current treatment strategies in CRC. In this review, we aim to summarize preclinical and clinical evidence for the utilization of liquid biopsy and gut microbiota in CRC.}, }
@article {pmid33534360, year = {2021}, author = {Ruan, W and Kellermayer, R}, title = {Alternative Diagnoses in Pediatric Fecal Microbiota Transplant Referral Patients.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {72}, number = {5}, pages = {693-696}, pmid = {33534360}, issn = {1536-4801}, mesh = {Adult ; Child ; *Clostridioides difficile ; *Clostridium Infections/diagnosis/therapy ; Fecal Microbiota Transplantation ; Humans ; Recurrence ; Referral and Consultation ; Retrospective Studies ; Treatment Outcome ; }, abstract = {ABSTRACT: The incidence of Clostridioides difficile infection (CDI) has been increasing in the United States. About 10-20% recur after initial treatment, with increasing recurrence following subsequent treatment courses. This sequence can lead to recurrent CDI (rCDI), refractory to conventional therapeutics resulting in the most common indication for fecal microbiota transplantation (FMT). FMT is the most effective microbial therapeutic to date and can cure rCDI in 80-90% of cases. There is growing concern, however, for pathogen transmission through FMT, underscoring the importance of careful recipient selection. In adults referred for FMT with a tentative diagnosis of rCDI, alternative diagnoses were recognized in 25% of patients, but such observation in children is lacking. In this single-center retrospective study, alternative diagnoses (eg, constipation/overflow diarrhea, inflammatory bowel disease) were found in 13 (22.4%) of 58 children who were referred for FMT evaluation for rCDI. Of the patients who were diagnosed with rCDI, 16 (27.6%) did not require FMT.}, }
@article {pmid33533699, year = {2020}, author = {Durham, SH and Le, P and Cassano, AT}, title = {Navigating changes in Clostridioides difficile prevention and treatment.}, journal = {Journal of managed care &amp; specialty pharmacy}, volume = {26}, number = {12-a Suppl}, pages = {S3-S23}, doi = {10.18553/jmcp.2020.26.12-a.s3}, pmid = {33533699}, issn = {2376-1032}, abstract = {Clostridioides difficile (C. difficile, previously known as Clostridium difficile) infections are a major health care concern. The Centers for Disease Control and Prevention (CDC) estimates that C. difficile causes almost half a million illnesses in the United States yearly, and approximately 1 in 5 patients with a C. difficile infection (CDI) will experience 1 or more recurrent infections. The incidence of infection has risen dramatically in recent years, and infection severity has increased due to the emergence of hypervirulent strains. There have been noteworthy advances in the development of CDI prevention and treatment, including a growth in the understanding of the role a patient's gut microbiome plays. The 2017 Infectious Diseases Society of America (IDSA) guidelines made a significant change in treatment recommendations for first time CDI episodes by recommending the use of oral vancomycin or fidaxomicin in place of metronidazole as a first-line treatment. The guidelines also included detailed recommendations on the use of fecal microbiota transplant (FMT) in those patients who experience 3 or more recurrent CDI episodes. A number of novel therapies for the treatment of CDI are in various stages of development. Treatments currently in phase 3 trials include the antibiotic ridinilazole, the microbiome products SER-109 and RBX2660, and a vaccine. All of these agents have shown promise in phase 1 and 2 trials. Additionally, several other antibiotic and microbiome candidates are currently in phase 1 or phase 2 trials. A qualitative review and evaluation of the literature on the cost-effectiveness of treatments for CDI in the U.S. setting was conducted, and the summary provided herein. Due to the higher cost of newer agents, cost-effectiveness evaluations will continue to be critical in clinical decision making for CDI. This paper reviews the updated CDI guidelines for prevention and treatment, the role of the microbiome in new and recurrent infections, pipeline medications, and comparative effectiveness research (CER) data on these treatments. DISCLOSURES: Durham and Le have nothing to disclose. Cassano reports consulting fees from Baxter Healthcare. Peer reviewers Drs. Ami Gopalan and Mark Rubin and Ms. Kathleen Jarvis have nothing to disclose. Planners Dr. Christine L. Cooper and Ms. Susan Yarbrough have nothing to disclose.}, }
@article {pmid33532747, year = {2020}, author = {Shin, W and Ambrosini, YM and Shin, YC and Wu, A and Min, S and Koh, D and Park, S and Kim, S and Koh, H and Kim, HJ}, title = {Robust Formation of an Epithelial Layer of Human Intestinal Organoids in a Polydimethylsiloxane-Based Gut-on-a-Chip Microdevice.}, journal = {Frontiers in medical technology}, volume = {2}, number = {}, pages = {}, pmid = {33532747}, issn = {2673-3129}, support = {F99 CA245801/CA/NCI NIH HHS/United States ; R21 CA236690/CA/NCI NIH HHS/United States ; }, abstract = {Polydimethylsiloxane (PDMS) is a silicone polymer that has been predominantly used in a human organ-on-a-chip microphysiological system. The hydrophobic surface of a microfluidic channel made of PDMS often results in poor adhesion of the extracellular matrix (ECM) as well as cell attachment. The surface modification by plasma or UV/ozone treatment in a PDMS-based device produces a hydrophilic surface that allows robust ECM coating and the reproducible attachment of human intestinal immortalized cell lines. However, these surface-activating methods have not been successful in forming a monolayer of the biopsy-derived primary organoid epithelium. Several existing protocols to grow human intestinal organoid cells in a PDMS microchannel are not always reproducibly operative due to the limited information. Here, we report an optimized methodology that enables robust and reproducible attachment of the intestinal organoid epithelium in a PDMS-based gut-on-a-chip. Among several reported protocols, we optimized a method by performing polyethyleneimine-based surface functionalization followed by the glutaraldehyde cross linking to activate the PDMS surface. Moreover, we discovered that the post-functionalization step contributes to provide uniform ECM deposition that allows to produce a robust attachment of the dissociated intestinal organoid epithelium in a PDMS-based microdevice. We envision that our optimized protocol may disseminate an enabling methodology to advance the integration of human organotypic cultures in a human organ-on-a-chip for patient-specific disease modeling.}, }
@article {pmid33532501, year = {2021}, author = {Diao, H and Xiao, Y and Yan, HL and Yu, B and He, J and Zheng, P and Yu, J and Mao, XB and Chen, DW}, title = {Effects of Early Transplantation of the Faecal Microbiota from Tibetan Pigs on the Gut Development of DSS-Challenged Piglets.}, journal = {BioMed research international}, volume = {2021}, number = {}, pages = {9823969}, pmid = {33532501}, issn = {2314-6141}, mesh = {Animals ; Animals, Suckling/growth &amp; development/physiology ; Dextran Sulfate ; Escherichia coli/genetics ; *Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome/genetics/physiology ; *Intestinal Mucosa/growth &amp; development/physiology ; Lactobacillus/genetics ; Swine ; }, abstract = {The present study was conducted to investigate the effects of early transplantation of the faecal microbiota from Tibetan pigs on the gut development of dextran sulphate sodium- (DSS-) challenged piglets. In total, 24 3-day-old DLY piglets were divided into four groups (n = 6 per group); a 2 × 2 factorial arrangement was used, which included faecal microbiota transplantation (FMT) (from Tibetan pigs) and DSS challenge. The whole trial lasted for 55 days. DSS infusion increased the intestinal density, serum diamine oxidase (DAO) activity, and colonic Escherichia coli count (P < 0.05), and decreased the Lactobacillus spp. count and mRNA abundances of epidermal growth factor (EGF), glucagon-like peptide-2 (GLP-2), insulin-like growth factor 1 (IGF-1), occludin, mucin 2 (MUC2), regeneration protein IIIγ (RegIIIγ), and interleukin-10 (IL-10) in the colon (P < 0.05). FMT increased the Lactobacillus spp. count and mRNA abundances of GLP-2, RegIIIγ, and IL-10 in the colon (P < 0.05), and decreased the intestinal density, serum DAO activity, and colonic E. coli number (P < 0.05). In addition, in DSS-challenged piglets, FMT decreased the disease activity index (P < 0.05) and attenuated the effect of DSS challenge on the intestinal density, serum DAO activity, and colonic E. coli number (P < 0.05). These data indicated that the faecal microbiota from Tibetan pigs could attenuate the negative effect of DSS challenge on the gut development of piglets.}, }
@article {pmid33531483, year = {2021}, author = {Littmann, ER and Lee, JJ and Denny, JE and Alam, Z and Maslanka, JR and Zarin, I and Matsuda, R and Carter, RA and Susac, B and Saffern, MS and Fett, B and Mattei, LM and Bittinger, K and Abt, MC}, title = {Host immunity modulates the efficacy of microbiota transplantation for treatment of Clostridioides difficile infection.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {755}, pmid = {33531483}, issn = {2041-1723}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; R00 AI125786/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; CD4-Positive T-Lymphocytes/immunology/metabolism ; CD8-Positive T-Lymphocytes/metabolism ; Clostridioides difficile/*pathogenicity ; Clostridium Infections/immunology/metabolism ; Feces/microbiology ; Forkhead Transcription Factors/metabolism ; Homeodomain Proteins/metabolism ; Inflammation/immunology/metabolism ; Mice ; T-Lymphocytes, Regulatory/immunology/metabolism ; }, abstract = {Fecal microbiota transplantation (FMT) is a successful therapeutic strategy for treating recurrent Clostridioides difficile infection. Despite remarkable efficacy, implementation of FMT therapy is limited and the mechanism of action remains poorly understood. Here, we demonstrate a critical role for the immune system in supporting FMT using a murine C. difficile infection system. Following FMT, Rag1 heterozygote mice resolve C. difficile while littermate Rag1-/- mice fail to clear the infection. Targeted ablation of adaptive immune cell subsets reveal a necessary role for CD4+ Foxp3+ T-regulatory cells, but not B cells or CD8+ T cells, in FMT-mediated resolution of C. difficile infection. FMT non-responsive mice exhibit exacerbated inflammation, impaired engraftment of the FMT bacterial community and failed restoration of commensal bacteria-derived secondary bile acid metabolites in the large intestine. These data demonstrate that the host's inflammatory immune status can limit the efficacy of microbiota-based therapeutics to treat C. difficile infection.}, }
@article {pmid33531405, year = {2021}, author = {Haifer, C and Paramsothy, S and Borody, TJ and Clancy, A and Leong, RW and Kaakoush, NO}, title = {Long-Term Bacterial and Fungal Dynamics following Oral Lyophilized Fecal Microbiota Transplantation in Clostridioides difficile Infection.}, journal = {mSystems}, volume = {6}, number = {1}, pages = {}, pmid = {33531405}, issn = {2379-5077}, abstract = {Oral lyophilized fecal microbiota transplantation (FMT) is effective in recurrent Clostridioides difficile infection (CDI); however, limited data exist on its efficacy in primary CDI and long-term microbial engraftment. Patients with primary or recurrent CDI were prospectively enrolled to receive oral FMT. Changes in the bacterial and fungal communities were characterized prior to and up to 6 months following treatment. A total of 37 patients with CDI (15 primary, 22 recurrent) were treated with 6 capsules each containing 0.35-g lyophilized stool extract. A total of 33 patients (89%) had sustained CDI cure, of whom 3 required a second course. There were no safety signals identified. FMT significantly increased bacterial diversity and shifted composition toward donor profiles in responders but not in nonresponders, with robust donor contribution observed to 6 months following FMT (P < 0.001). Responders showed consistent decreases in Enterobacteriaceae and increases in Faecalibacterium sp. to levels seen in donors. Mycobiome profiling revealed an association with FMT failure and increases in one Penicillium taxon, as well as coexclusion relationships between Candida sp. and bacterial taxa enriched in both donors and responders. Primary CDI was associated with more robust changes in the bacterial community than those with recurrent disease. Oral FMT leads to durable microbial engraftment in patients with primary and recurrent CDI, with several microbial taxa being associated with therapy outcome. Novel coexclusion relationships between bacterial and fungal species support the clinical relevance of transkingdom dynamics.IMPORTANCE Clostridioides difficile infection (CDI) is a substantial health concern worldwide, complicated by patterns of increasing antibiotic resistance that may impact primary treatment. Orally administered fecal microbiota transplantation (FMT) is efficacious in the management of recurrent CDI, with specific bacterial species known to influence clinical outcomes. To date, little is known about the efficacy of FMT in primary CDI and the impact of the mycobiome on therapeutic outcomes. We performed matched bacterial and fungal sequencing on longitudinal samples from a cohort of patients treated with oral FMT for primary and recurrent CDI. We validated many bacterial signatures following oral therapy, confirmed engraftment of donor microbiome out to 6 months following therapy, and demonstrated coexclusion relationships between Candida albicans and two bacterial species in the gut microbiota, which has potential significance beyond CDI, including in the control of gut colonization by this fungal species.}, }
@article {pmid33529409, year = {2021}, author = {Subba, R and Sandhir, R and Singh, SP and Mallick, BN and Mondal, AC}, title = {Pathophysiology linking depression and type 2 diabetes: Psychotherapy, physical exercise, and fecal microbiome transplantation as damage control.}, journal = {The European journal of neuroscience}, volume = {53}, number = {8}, pages = {2870-2900}, doi = {10.1111/ejn.15136}, pmid = {33529409}, issn = {1460-9568}, mesh = {Depression/therapy ; *Diabetes Mellitus, Type 2/therapy ; Exercise ; Fecal Microbiota Transplantation ; Humans ; Hypothalamo-Hypophyseal System ; *Microbiota ; Pituitary-Adrenal System ; Psychotherapy ; }, abstract = {Diabetes increases the likelihood of developing depression and vice versa. Research on this bidirectional association has somewhat managed to delineate the interplay among implicated physiological processes. Still, further exploration is required in this context. This review addresses the comorbidity by investigating suspected common pathophysiological mechanisms. One such factor is psychological stress which disturbs the hypothalamic-pituitary-adrenal axis causing hormonal imbalance. This includes elevated cortisol levels, a common biomarker of both depression and diabetes. Disrupted insulin signaling drives the hampered neurotransmission of serotonin, dopamine, and norepinephrine. Also, adipokine hormones such as adiponectin, leptin, and resistin and the orexigenic hormone, ghrelin, are involved in both depression and T2DM. This disarray further interferes with physiological processes encompassing sleep, the gut-brain axis, metabolism, and mood stability. Behavioral coping mechanisms, such as unhealthy eating, mediate disturbed glucose homeostasis, and neuroinflammation. This is intricately linked to oxidative stress, redox imbalance, and mitochondrial dysfunction. However, interventions such as psychotherapy, physical exercise, fecal microbiota transplantation, and insulin-sensitizing agents can help to manage the distressing condition. The possibility of glucagon-like peptide 1 possessing a therapeutic role has also been discussed. Nonetheless, there stands an urgent need for unraveling new correlating targets and biological markers for efficient treatment.}, }
@article {pmid33523449, year = {2021}, author = {Liu, Y and Tran, DQ and Lindsey, JW and Rhoads, JM}, title = {The Association of Gut Microbiota and Treg Dysfunction in Autoimmune Diseases.}, journal = {Advances in experimental medicine and biology}, volume = {1278}, number = {}, pages = {191-203}, pmid = {33523449}, issn = {0065-2598}, support = {R01 AT007083/AT/NCCIH NIH HHS/United States ; R03 AI117442/AI/NIAID NIH HHS/United States ; }, mesh = {*Autoimmune Diseases/therapy ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Inflammatory Bowel Diseases ; T-Lymphocytes, Regulatory ; }, abstract = {Autoimmune conditions affect 23 million Americans or 7% of the US population. There are more than 100 autoimmune disorders, affecting every major organ system in humans. This chapter aims to further explain Treg dysfunction autoimmune disorders, including monogenic primary immune deficiency such as immune dysregulation polyendocrinopathy, enteropathy, X-linked inheritance (IPEX) syndrome, and polygenic autoimmune diseases with Treg dysfunction such as multiple sclerosis (MS), inflammatory bowel disease (IBD), and food allergy. These conditions are associated with an abnormal small intestinal and colonic microbiome. Some disorders clearly improve with therapies aimed at microbial modification, including probiotics and fecal microbiota transplantation (FMT). Approaches to prevent and treat these disorders will need to focus on the acquisition and maintenance of a healthy colonic microbiota, in addition to more focused approaches at immune suppression during acute disease exacerbations.}, }
@article {pmid33521100, year = {2021}, author = {Zheng, L and Wen, XL}, title = {Gut microbiota and inflammatory bowel disease: The current status and perspectives.}, journal = {World journal of clinical cases}, volume = {9}, number = {2}, pages = {321-333}, pmid = {33521100}, issn = {2307-8960}, abstract = {Inflammatory bowel disease (IBD) is a chronic immune-mediated disease that affects the gastrointestinal tract. It is argued that environment, microbiome, and immune-mediated factors interact in a genetically susceptible host to trigger IBD. Recently, there has been increased interest in the development, progression, and treatment of IBD because of our understanding of the microbiome. Researchers have proved that some factors can alter the microbiome and the pathogenesis of IBD. As a result, there has been increasing interest in the application of probiotics, prebiotics, antibiotics, fecal microbiota transplantation, and gene manipulation in treating IBD because of the possible curative effect of microbiome-modulating interventions. In this review, we summarize the findings from human and animal studies and discuss the effect of the gut microbiome in treating patients with IBD.}, }
@article {pmid33517890, year = {2021}, author = {Hou, YF and Shan, C and Zhuang, SY and Zhuang, QQ and Ghosh, A and Zhu, KC and Kong, XK and Wang, SM and Gong, YL and Yang, YY and Tao, B and Sun, LH and Zhao, HY and Guo, XZ and Wang, WQ and Ning, G and Gu, YY and Li, ST and Liu, JM}, title = {Gut microbiota-derived propionate mediates the neuroprotective effect of osteocalcin in a mouse model of Parkinson's disease.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {34}, pmid = {33517890}, issn = {2049-2618}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Disease Models, Animal ; Disease Progression ; Dopaminergic Neurons/drug effects ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/*physiology ; Infusions, Parenteral ; Male ; Mice ; Neuroprotective Agents/administration &amp; dosage/*pharmacology ; Osteocalcin/administration &amp; dosage/*pharmacology ; Oxidopamine ; Parkinson Disease/*drug therapy/*metabolism/microbiology/physiopathology ; Propionates/*metabolism ; Receptors, G-Protein-Coupled/agonists/metabolism ; }, abstract = {BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder with no absolute cure. The evidence of the involvement of gut microbiota in PD pathogenesis suggests the need to identify certain molecule(s) derived from the gut microbiota, which has the potential to manage PD. Osteocalcin (OCN), an osteoblast-secreted protein, has been shown to modulate brain function. Thus, it is of interest to investigate whether OCN could exert protective effect on PD and, if yes, whether the underlying mechanism lies in the subsequent changes in gut microbiota.<br><br>RESULTS: The intraperitoneal injection of OCN can effectively ameliorate the motor deficits and dopaminergic neuronal loss in a 6-hydroxydopamine-induced PD mouse model. The further antibiotics treatment and fecal microbiota transplantation experiments confirmed that the gut microbiota was required for OCN-induced protection in PD mice. OCN elevated Bacteroidetes and depleted Firmicutes phyla in the gut microbiota of PD mice with elevated potential of microbial propionate production and was confirmed by fecal propionate levels. Two months of orally administered propionate successfully rescued motor deficits and dopaminergic neuronal loss in PD mice. Furthermore, AR420626, the agonist of FFAR3, which is the receptor of propionate, mimicked the neuroprotective effects of propionate and the ablation of enteric neurons blocked the prevention of dopaminergic neuronal loss by propionate in PD mice.<br><br>CONCLUSIONS: Together, our results demonstrate that OCN ameliorates motor deficits and dopaminergic neuronal loss in PD mice, modulating gut microbiome and increasing propionate level might be an underlying mechanism responsible for the neuroprotective effects of OCN on PD, and the FFAR3, expressed in enteric nervous system, might be the main action site of propionate. Video abstract.}, }
@article {pmid33512409, year = {2021}, author = {Khan, N and Lindner, S and Gomes, ALC and Devlin, SM and Shah, GL and Sung, AD and Sauter, CS and Landau, HJ and Dahi, PB and Perales, MA and Chung, DJ and Lesokhin, AM and Dai, A and Clurman, A and Slingerland, JB and Slingerland, AE and Brereton, DG and Giardina, PA and Maloy, M and Armijo, GK and Rondon-Clavo, C and Fontana, E and Bohannon, L and Ramalingam, S and Bush, AT and Lew, MV and Messina, JA and Littmann, E and Taur, Y and Jenq, RR and Chao, NJ and Giralt, S and Markey, KA and Pamer, EG and van den Brink, MRM and Peled, JU}, title = {Fecal microbiota diversity disruption and clinical outcomes after auto-HCT: a multicenter observational study.}, journal = {Blood}, volume = {137}, number = {11}, pages = {1527-1537}, pmid = {33512409}, issn = {1528-0020}, support = {P01 CA023766/CA/NCI NIH HHS/United States ; R01 CA228308/CA/NCI NIH HHS/United States ; R01 HL147584/HL/NHLBI NIH HHS/United States ; R21 AG066388/AG/NIA NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; KL2 TR001115/TR/NCATS NIH HHS/United States ; R01 HL125571/HL/NHLBI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P01 AG052359/AG/NIA NIH HHS/United States ; P30 AG028716/AG/NIA NIH HHS/United States ; R01 CA228358/CA/NCI NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; R01 CA203950/CA/NCI NIH HHS/United States ; R01 AI137269/AI/NIAID NIH HHS/United States ; R01 HL123340/HL/NHLBI NIH HHS/United States ; }, abstract = {We previously described clinically relevant reductions in fecal microbiota diversity in patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). Recipients of high-dose chemotherapy and autologous HCT (auto-HCT) incur similar antibiotic exposures and nutritional alterations. To characterize the fecal microbiota in the auto-HCT population, we analyzed 1161 fecal samples collected from 534 adult recipients of auto-HCT for lymphoma, myeloma, and amyloidosis in an observational study conducted at 2 transplantation centers in the United States. By using 16S ribosomal gene sequencing, we assessed fecal microbiota composition and diversity, as measured by the inverse Simpson index. At both centers, the diversity of early pretransplant fecal microbiota was lower in patients than in healthy controls and decreased further during the course of transplantation. Loss of diversity and domination by specific bacterial taxa occurred during auto-HCT in patterns similar to those with allo-HCT. Above-median fecal intestinal diversity in the periengraftment period was associated with decreased risk of death or progression (progression-free survival hazard ratio, 0.46; 95% confidence interval, 0.26-0.82; P = .008), adjusting for disease and disease status. This suggests that further investigation into the health of the intestinal microbiota in auto-HCT patients and posttransplant outcomes should be undertaken.}, }
@article {pmid33511356, year = {2021}, author = {Helve, O and Dikareva, E and Stefanovic, V and Kolho, KL and Salonen, A and de Vos, WM and Andersson, S}, title = {Protocol for oral transplantation of maternal fecal microbiota to newborn infants born by cesarean section.}, journal = {STAR protocols}, volume = {2}, number = {1}, pages = {100271}, pmid = {33511356}, issn = {2666-1667}, abstract = {Infants born by cesarean section have an intestinal microbiota that differs from that of infants delivered vaginally. Here, we report a protocol for performing oral transplantation of maternal fecal microbiota to newborn infants born by elective cesarean section. The crucial step of this protocol is the health screening process. This protocol can only be applied to healthy mothers and infants. For complete details on the use and execution of this protocol, please refer to Korpela et al. (2020).}, }
@article {pmid33510784, year = {2021}, author = {Xu, HM and Huang, HL and Zhou, YL and Zhao, HL and Xu, J and Shou, DW and Liu, YD and Zhou, YJ and Nie, YQ}, title = {Fecal Microbiota Transplantation: A New Therapeutic Attempt from the Gut to the Brain.}, journal = {Gastroenterology research and practice}, volume = {2021}, number = {}, pages = {6699268}, pmid = {33510784}, issn = {1687-6121}, abstract = {Gut dysbacteriosis is closely related to various intestinal and extraintestinal diseases. Fecal microbiota transplantation (FMT) is a biological therapy that entails transferring the gut microbiota from healthy individuals to patients in order to reconstruct the intestinal microflora in the latter. It has been proved to be an effective treatment for recurrent Clostridium difficile infection. Studies show that the gut microbiota plays an important role in the pathophysiology of neurological and psychiatric disorders through the microbiota-gut-brain axis. Therefore, reconstruction of the healthy gut microbiota is a promising new strategy for treating cerebral diseases. We have reviewed the latest research on the role of gut microbiota in different nervous system diseases as well as FMT in the context of its application in neurological, psychiatric, and other nervous system-related diseases (Parkinson's disease, Alzheimer's disease, multiple sclerosis, epilepsy, autism spectrum disorder, bipolar disorder, hepatic encephalopathy, neuropathic pain, etc.).}, }
@article {pmid33510783, year = {2021}, author = {Zhong, M and Buch, H and Wen, Q and Long, C and Cui, B and Zhang, F}, title = {Colonic Transendoscopic Enteral Tubing: Route for a Novel, Safe, and Convenient Delivery of Washed Microbiota Transplantation in Children.}, journal = {Gastroenterology research and practice}, volume = {2021}, number = {}, pages = {6676962}, pmid = {33510783}, issn = {1687-6121}, abstract = {Aim: Colonic transendoscopic enteral tubing (TET) has been used for delivering fecal microbiota transplantation by washed preparation since 2015, which was recently named as washed microbiota transplantation (WMT). However, there are few reports available regarding the feasibility and safety of these studies in low-age population. This study is aimed at evaluating the safety, feasibility, and value of colonic TET in 3-7 years old children.<br><br>Methods: All patients aged 3-7 years who underwent colonic TET in our center for WMT or medication were prospectively evaluated. The feasibility and safety of TET were evaluated. A questionnaire was completed by the children's parents to evaluate the children's response to the colonic TET as well as the parent's satisfaction.<br><br>Results: Forty-seven children were included (mean age 5 years). TET was implemented into the colon of all the patients, and the success rate of the procedure was 100%. The median retention time of TET tube within the colon was 6 (IQR 5-7) days in 45 patients with tube falling out spontaneously, and the maximum retention time was up to 21 days. Multivariate analysis demonstrated that endoscopic clip number (P = 0.009) was an independent contributing factor for the retaining time of tube. With increase in the number of large clips, the retention time of TET tube was prolonged. No discomfort was reported during injection of the microbiota or medication suspension through the TET tube. During the follow-up, no severe adverse events were observed. All children's parents were satisfied with TET. Interestingly, the proportion of children's parents choosing TET as the delivery way of WMT increased from 29.79% before to 70.21% after TET (P < 0.001).<br><br>Conclusions: This study, for the first time, demonstrates that colonic TET is a novel, safe, and convenient colonic delivery way for WMT and medication in children aged 3-7 years.}, }
@article {pmid33508620, year = {2021}, author = {Li, X and Kang, Y and Huang, Y and Xiao, Y and Song, L and Lu, S and Ren, Z}, title = {A strain of Bacteroides thetaiotaomicron attenuates colonization of Clostridioides difficile and affects intestinal microbiota and bile acids profile in a mouse model.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {137}, number = {}, pages = {111290}, doi = {10.1016/j.biopha.2021.111290}, pmid = {33508620}, issn = {1950-6007}, mesh = {Animals ; Bacteroides thetaiotaomicron/*growth &amp; development ; Bile Acids and Salts/*metabolism ; Clostridioides difficile/*pathogenicity ; Clostridium Infections/metabolism/microbiology/*prevention &amp; control ; Colon/*microbiology ; Disease Models, Animal ; Feces/chemistry/microbiology ; Female ; *Gastrointestinal Microbiome ; Host-Pathogen Interactions ; Mice, Inbred C57BL ; *Probiotics ; }, abstract = {Clostridioides difficile infection (CDI) is a growing global public health threat. While fecal microbiota transplantation (FMT) is an effective therapy for CDI, a number of challenges limit its application. Studies suggest that probiotics may be a promising alternative therapy. In the current study, we evaluated whether Bacteroides thetaiotaomicron (B. thetaiotaomicron) would inhibit colonization of toxigenic BI/NAP1/027 C. difficile in a mouse model. We found that B. thetaiotaomicron administration decreased the copies of C. difficile and inhibited inflammation in the colon. 16S rRNA sequencing showed that B. thetaiotaomicron administration was associated with a significantly increased relative abundance of Bacteroidetes and decreased level of Proteobacteria, leading to the reversal of the effect of antibiotics treatment and C. difficile infection on microbiota. B. thetaiotaomicron administration was associated with increases in the concentrations of alpha-muricholic acid, beta-muricholic acid, 12 ketolithocholic acid, and deoxycholic acid which are known to inhibit the growth of C. difficile, as well as reductions in the level of taurocholic acid, which promotes germination of C. difficile. Altered profile of major high abundance bile acids by B. thetaiotaomicron administration was similar to that with FMT treatment. Based on these results, we proposed the concept of "the ratio of promotion/inhibition BAs" which would advance our understanding of the relation of C. difficile and BAs.}, }
@article {pmid33508265, year = {2021}, author = {Ait Yahia, S and Audousset, C and Alvarez-Simon, D and Vorng, H and Togbe, D and Marquillies, P and Delacre, M and Rose, S and Bouscayrol, H and Rifflet, A and Quesniaux, V and Boneca, IG and Chamaillard, M and Tsicopoulos, A}, title = {NOD1 sensing of house dust mite-derived microbiota promotes allergic experimental asthma.}, journal = {The Journal of allergy and clinical immunology}, volume = {148}, number = {2}, pages = {394-406}, doi = {10.1016/j.jaci.2020.12.649}, pmid = {33508265}, issn = {1097-6825}, abstract = {BACKGROUND: Asthma severity has been linked to exposure to gram-negative bacteria from the environment that are recognized by NOD1 receptor and are present in house dust mite (HDM) extracts. NOD1 polymorphism has been associated with asthma.<br><br>OBJECTIVE: We sought to evaluate whether either host or HDM-derived microbiota may contribute to NOD1-dependent disease severity.<br><br>METHODS: A model of HDM-induced experimental asthma was used and the effect of NOD1 deficiency was evaluated. Contribution of host microbiota was evaluated by fecal transplantation. Contribution of HDM-derived microbiota was assessed by 16S ribosomal RNA sequencing, mass spectrometry analysis, and peptidoglycan depletion of the extracts.<br><br>RESULTS: In this model, loss of the bacterial sensor NOD1 and its adaptor RIPK2 improved asthma features. Such inhibitory effect was not related to dysbiosis caused by NOD1 deficiency, as shown by fecal transplantation of Nod1-deficient microbiota to wild-type germ-free mice. The 16S ribosomal RNA gene sequencing and mass spectrometry analysis of HDM allergen, revealed the presence of some muropeptides from gram-negative bacteria that belong to the Bartonellaceae family. While such HDM-associated muropeptides were found to activate NOD1 signaling in epithelial cells, peptidoglycan-depleted HDM had a decreased ability to instigate asthma in vivo.<br><br>CONCLUSIONS: These data show that NOD1-dependent sensing of HDM-associated gram-negative bacteria aggravates the severity of experimental asthma, suggesting that inhibiting the NOD1 signaling pathway may be a therapeutic approach to treating asthma.}, }
@article {pmid33506928, year = {2021}, author = {Nakov, R and Lyutakov, I and Mitkova, A and Gerova, V and Petkova, V and Giragosyan, S and Vatcheva-Dobrevska, R and Kaneva, R and Nakov, V}, title = {Establishment of the first stool bank in an Eastern European country and the first series of successful fecal microbiota transplantations in Bulgaria.}, journal = {European review for medical and pharmacological sciences}, volume = {25}, number = {1}, pages = {390-396}, doi = {10.26355/eurrev_202101_24406}, pmid = {33506928}, issn = {2284-0729}, mesh = {Adult ; Aged ; Bulgaria ; Colonoscopy ; Enterocolitis, Pseudomembranous/*therapy ; Europe ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Middle Aged ; Surveys and Questionnaires ; Young Adult ; }, abstract = {OBJECTIVE: For safe implementation and broader application of fecal microbiota transplantation (FMT), quality controlled stool banking is a must. Establishing a stool bank is a complex, time-consuming, and expensive process, making it a real challenge in an Eastern European country. We aimed to establish the first stool bank in Eastern Europe - in Bulgaria.<br><br>SUBJECTS AND METHODS: A multidisciplinary team of gastroenterologists, microbiologists, infectionists, and geneticists was set up. We used a questionnaire based on the First European FMT Consensus in order to recruit possible stool donors. Laboratory blood and stool tests were performed on all potential donors.<br><br>RESULTS: Between October 2018 and April 2019, 112 donor volunteers completed a questionnaire; 70 (62.5%) were excluded, mainly because of age above 50, an unhealthy BMI, and risk behavior. Fourty-two (37.5%) donor candidates were invited for laboratory testing of blood and feces, of which 12 (28.6%) passed this screening. Of 12 donors, 4 (33%) failed at the following screening test, which is performed every 3-6 months. Finally, 8 (7.14%) active donors were enrolled. Ten successful FMTs were performed on patients with recurrent Clostridium difficile infection.<br><br>CONCLUSIONS: Even though we found many healthy volunteers, only a low percentage (7.14%) of them were suitable to become feces donors. Establishing a stool bank in an Eastern European country is essential for making FMT safe and more popular as a treatment method, finding further implementation and regulation of FMT and supporting physicians offering this treatment to their patients.}, }
@article {pmid33505139, year = {2020}, author = {Qi, X and Yang, M and Stenberg, J and Dey, R and Fogwe, L and Alam, MS and Kimchi, ET and Staveley-O'Carroll, KF and Li, G}, title = {Gut microbiota mediated molecular events and therapy in liver diseases.}, journal = {World journal of gastroenterology}, volume = {26}, number = {48}, pages = {7603-7618}, pmid = {33505139}, issn = {2219-2840}, support = {R01 CA208396/CA/NCI NIH HHS/United States ; }, mesh = {Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; Liver ; *Non-alcoholic Fatty Liver Disease/therapy ; *Probiotics/therapeutic use ; }, abstract = {Gut microbiota is a community of microorganisms that reside in the gastrointestinal tract. An increasing number of studies has demonstrated that the gut-liver axis plays a critical role in liver homeostasis. Dysbiosis of gut microbiota can cause liver diseases, including nonalcoholic fatty liver disease and alcoholic liver disease. Preclinical and clinical investigations have substantiated that the metabolites and other molecules derived from gut microbiota and diet interaction function as mediators to cause liver fibrosis, cirrhosis, and final cancer. This effect has been demonstrated to be associated with dysregulation of intrahepatic immunity and liver metabolism. Targeting these findings have led to the development of novel preventive and therapeutic strategies. Here, we review the cellular and molecular mechanisms underlying gut microbiota-mediated impact on liver disease. We also summarize the advancement of gut microbiota-based therapeutic strategies in the control of liver diseases.}, }
@article {pmid33504365, year = {2021}, author = {Hao, X and Shang, X and Liu, J and Chi, R and Zhang, J and Xu, T}, title = {The gut microbiota in osteoarthritis: where do we stand and what can we do?.}, journal = {Arthritis research &amp; therapy}, volume = {23}, number = {1}, pages = {42}, pmid = {33504365}, issn = {1478-6362}, mesh = {Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; Inflammation ; *Osteoarthritis/therapy ; Quality of Life ; }, abstract = {Osteoarthritis (OA) is one of the most frequent musculoskeletal diseases characterized by degeneration of articular cartilage, subchondral bone remodeling, and synovial membrane inflammation, which is a leading cause of global disability, morbidity, and decreased quality of life. Interpreting the potential mechanisms of OA pathogenesis is essential for developing novel prevention and disease-modifying therapeutic interventions. Gut microbiota is responsible for a series of metabolic, immunological, and structural and neurological functions, potentially elucidating the heterogeneity of OA phenotypes and individual features. In this narrative review, we summarized research evidence supporting the hypothesis of a "gut-joint axis" and the interaction between gut microbiota and the OA-relevant factors, including age, gender, genetics, metabolism, central nervous system, and joint injury, elucidating the underlying mechanisms of this intricate interaction. In the context, we also speculated the promising manipulation of gut microbiota in OA management, such as exercise and fecal microbiota transplantation (FMT), highlighting the clinical values of gut microbiota. Additionally, future research directions, such as more convincing studies by the interventions of gut microbiota, the gene regulation of host contributing to or attributed to the specific phenotypes of gut microbiota related to OA, and the relevance of distinct cell subgroups to gut microbiota, are expected. Moreover, gut microbiota is also the potential biomarker related to inflammation and gut dysbiosis that is able to predict OA progression and monitor the efficacy of therapeutic intervention.}, }
@article {pmid33501942, year = {2021}, author = {Karjalainen, EK and Renkonen-Sinisalo, L and Satokari, R and Mustonen, H and Ristimäki, A and Arkkila, P and Lepistö, AH}, title = {Fecal Microbiota Transplantation in Chronic Pouchitis: A Randomized, Parallel, Double-Blinded Clinical Trial.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izab001}, pmid = {33501942}, issn = {1536-4844}, abstract = {BACKGROUND: In ulcerative colitis, a pouchitis is the most common long-term adverse effect after proctocolectomy and ileal pouch-anal anastomosis. Approximately 5% of patients develop chronic antibiotic-dependent or antibiotic-refractory pouchitis without any effective treatment. The aim of this trial was to investigate the efficacy and safety of fecal microbiota transplantation in the treatment of chronic pouchitis.<br><br>METHODS: This was a single-center, double-blinded, parallel group trial comparing donor fecal microbiota transplantation with placebo (autologous transplant) in chronic pouchitis. Twenty-six patients were recruited at the Helsinki University Hospital between December 2017 and August 2018 and were randomly allocated a 1:1 ratio to either donor fecal microbiota transplantation or placebo. The protocol included 2 transplantations into the pouch on weeks 0 and 4, and patients were followed up for 52 weeks.<br><br>RESULTS: Nine patients in the intervention group and 8 patients in the placebo group relapsed during the 52-week follow-up, and the relapse-free survival did not differ between the groups (P = 0.183, log-rank; hazard ratio, 1.90 [95% confidence interval, 0.73-4.98; P = 0.190]). In the subgroup analysis of patients using continuous antibiotics before the study, the relapse-free survival was shorter in the intervention group (P = 0.004, log-rank; hazard ratio, 13.08 [95% confidence interval, 1.47-116.60; P = 0.021]). No major adverse effects were reported.<br><br>CONCLUSIONS: The fecal microbiota transplantation treatment regime used in our study was not effective in the treatment of chronic pouchitis. The safety profile of fecal microbiota transplantation was good.<br><br>CLINICALTRIALS.GOV IDENTIFIER: NCT03378921.}, }
@article {pmid33501941, year = {2021}, author = {Dalal, RS and Allegretti, JR}, title = {Fecal Microbiota Transplantation for Chronic Pouchitis: Promising Novel Therapeutic or Lost Cause?.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izab002}, pmid = {33501941}, issn = {1536-4844}, }
@article {pmid33501940, year = {2021}, author = {Karjalainen, EK and Renkonen-Sinisalo, L and Satokari, R and Mustonen, H and Ristimäki, A and Arkkila, P and Lepistö, AH}, title = {Author's Reply: Fecal Microbiota Transplantation for Chronic Pouchitis: Promising Novel Therapeutic or Lost Cause?.}, journal = {Inflammatory bowel diseases}, volume = {27}, number = {7}, pages = {e79-e80}, doi = {10.1093/ibd/izab003}, pmid = {33501940}, issn = {1536-4844}, }
@article {pmid33501400, year = {2020}, author = {Utay, NS and Monczor, AN and Somasunderam, A and Lupo, S and Jiang, ZD and Alexander, AS and Finkelman, M and Vigil, KJ and Lake, JE and Hanson, B and DuPont, HL and Arduino, RC}, title = {Evaluation of Six Weekly Oral Fecal Microbiota Transplants in People with HIV.}, journal = {Pathogens &amp; immunity}, volume = {5}, number = {1}, pages = {364-381}, pmid = {33501400}, issn = {2469-2964}, abstract = {Background: Reduced microbiota diversity (dysbiosis) in people with HIV (PWH) likely contributes to inflammation, a driver of morbidity and mortality. We aimed to evaluate the safety and tolerability of 6 weekly oral fecal microbiota transplants (FMT) administered to reverse this dysbiosis.<br><br>Methods: Six PWH on suppressive antiretroviral therapy (ART) received 6 weekly doses of lyophilized fecal microbiota product from healthy donors. Shotgun sequencing on stool before, after last FMT, and 20 weeks thereafter was performed. Inflammation and gut permeability biomarkers were measured.<br><br>Results: Median age at week 0 was 39 years, CD4+ T cell count 496 cells/mm3, HIV RNA levels <20 copies/mL. FMT was safe and well-tolerated. α diversity increased in 4 participants from weeks 0 to 6, including the 3 with the lowest α diversity at week 0. At week 26, α diversity more closely resembled week 0 than week 6 in these 4 participants. Metagenomic analysis showed no consistent changes across all participants. One participant had high gut permeability and inflammation biomarker levels and low α diversity that improved between weeks 0 and 6 with a shift in distribution.<br><br>Conclusions: Weekly FMT was safe and well-tolerated. α diversity increased in participants with the lowest baseline α diversity during the treatment period. Future randomized, controlled trials of FMT should consider evaluating PWH with greater inflammation, gut damage, or dysbiosis as this population may be most likely to show a significant response.ClinicalTrials.gov Identifier: NCT03329560.}, }
@article {pmid33500411, year = {2021}, author = {Uzan-Yulzari, A and Turta, O and Belogolovski, A and Ziv, O and Kunz, C and Perschbacher, S and Neuman, H and Pasolli, E and Oz, A and Ben-Amram, H and Kumar, H and Ollila, H and Kaljonen, A and Isolauri, E and Salminen, S and Lagström, H and Segata, N and Sharon, I and Louzoun, Y and Ensenauer, R and Rautava, S and Koren, O}, title = {Neonatal antibiotic exposure impairs child growth during the first six years of life by perturbing intestinal microbial colonization.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {443}, pmid = {33500411}, issn = {2041-1723}, mesh = {Animals ; Anti-Bacterial Agents/*adverse effects ; Bacterial Infections/*drug therapy ; Body Height/drug effects/physiology ; Body Mass Index ; Body Weight/drug effects/physiology ; Child ; Child, Preschool ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Follow-Up Studies ; Gastrointestinal Microbiome/*drug effects/physiology ; Germ-Free Life ; Growth Disorders/*chemically induced/microbiology/physiopathology ; Humans ; Infant, Newborn ; Intestinal Mucosa/microbiology ; Male ; Mice ; Pregnancy ; Risk Factors ; Sex Factors ; }, abstract = {Exposure to antibiotics in the first days of life is thought to affect various physiological aspects of neonatal development. Here, we investigate the long-term impact of antibiotic treatment in the neonatal period and early childhood on child growth in an unselected birth cohort of 12,422 children born at full term. We find significant attenuation of weight and height gain during the first 6 years of life after neonatal antibiotic exposure in boys, but not in girls, after adjusting for potential confounders. In contrast, antibiotic use after the neonatal period but during the first 6 years of life is associated with significantly higher body mass index throughout the study period in both boys and girls. Neonatal antibiotic exposure is associated with significant differences in the gut microbiome, particularly in decreased abundance and diversity of fecal Bifidobacteria until 2 years of age. Finally, we demonstrate that fecal microbiota transplant from antibiotic-exposed children to germ-free male, but not female, mice results in significant growth impairment. Thus, we conclude that neonatal antibiotic exposure is associated with a long-term gut microbiome perturbation and may result in reduced growth in boys during the first six years of life while antibiotic use later in childhood is associated with increased body mass index.}, }
@article {pmid33499991, year = {2020}, author = {Sidiropoulos, DN and Al-Ghalith, GA and Shields-Cutler, RR and Ward, TL and Johnson, AJ and Vangay, P and Knights, D and Kashyap, PC and Xian, Y and Ramer-Tait, AE and Clayton, JB}, title = {Wild primate microbiomes prevent weight gain in germ-free mice.}, journal = {Animal microbiome}, volume = {2}, number = {1}, pages = {16}, pmid = {33499991}, issn = {2524-4671}, support = {T32 DA007097-32/DA/NIDA NIH HHS/United States ; DK114007//Foundation for the National Institutes of Health/ ; }, abstract = {BACKGROUND: The gut microbiome harbors trillions of bacteria that play a major role in dietary nutrient extraction and host metabolism. Metabolic diseases such as obesity and diabetes are associated with shifts in microbiome composition and have been on the rise in Westernized or highly industrialized countries. At the same time, Westernized diets low in dietary fiber have been shown to cause loss of gut microbial diversity. However, the link between microbiome composition, loss of dietary fiber, and obesity has not been well defined.<br><br>RESULTS: To study the interactions between gut microbiota, dietary fiber, and weight gain, we transplanted captive and wild douc gut microbiota into germ-free mice and then exposed them to either a high- or low-fiber diet. The group receiving captive douc microbiota gained significantly more weight, regardless of diet, while mice receiving a high-fiber diet and wild douc microbiota remained lean. In the presence of a low-fiber diet, the wild douc microbiota partially prevented weight gain. Using 16S rRNA gene amplicon sequencing we identified key bacterial taxa in each group, specifically a high relative abundance of Bacteroides and Akkermansia in captive douc FMT mice and a higher relative abundance of Lactobacillus and Clostridium in the wild douc FMT mice.<br><br>CONCLUSIONS: In the context of our germ-free mouse experiment, wild douc microbiota could serve as a reservoir for microbes for cross-species transplants. Our results suggest that wild douc microbiota are tailored to diverse fiber diets and can prevent weight gain when exposed to a native diet.}, }
@article {pmid33498428, year = {2021}, author = {Kampouri, E and Croxatto, A and Prod'hom, G and Guery, B}, title = {Clostridioides difficile Infection, Still a Long Way to Go.}, journal = {Journal of clinical medicine}, volume = {10}, number = {3}, pages = {}, pmid = {33498428}, issn = {2077-0383}, abstract = {Clostridioides difficile is an increasingly common pathogen both within and outside the hospital and is responsible for a large clinical spectrum from asymptomatic carriage to complicated infection associated with a high mortality. While diagnostic methods have considerably progressed over the years, the optimal diagnostic algorithm is still debated and there is no single diagnostic test that can be used as a standalone test. More importantly, the heterogeneity in diagnostic practices between centers along with the lack of robust surveillance systems in all countries and an important degree of underdiagnosis due to lack of clinical suspicion in the community, hinder a more accurate evaluation of the burden of disease. Our improved understanding of the physiopathology of CDI has allowed some significant progress in the treatment of CDI, including a broader use of fidaxomicine, the use of fecal microbiota transplantation for multiples recurrences and newer approaches including antibodies, vaccines and new molecules, already developed or in the pipeline. However, the management of CDI recurrences and severe infections remain challenging and the main question remains: how to best target these often expensive treatments to the right population. In this review we discuss current diagnostic approaches, treatment and potential prevention strategies, with a special focus on recent advances in the field as well as areas of uncertainty and unmet needs and how to address them.}, }
@article {pmid33497754, year = {2021}, author = {Settanni, CR and Ianiro, G and Bibbò, S and Cammarota, G and Gasbarrini, A}, title = {Gut microbiota alteration and modulation in psychiatric disorders: Current evidence on fecal microbiota transplantation.}, journal = {Progress in neuro-psychopharmacology &amp; biological psychiatry}, volume = {109}, number = {}, pages = {110258}, doi = {10.1016/j.pnpbp.2021.110258}, pmid = {33497754}, issn = {1878-4216}, abstract = {The micro-organisms residing within the gastrointestinal tract, namely gut microbiota, form a dynamic population proper of each individual, mostly composed by bacteria which co-evolved symbiotically with human species. The advances of culture-independent techniques allowed the understanding of the multiple functions of the gut microbiota in human physiology and disease, the latter often recognising a predisposing condition in an imbalanced intestinal microbial ecosystem (dysbiosis). A complex mutual interconnection between the central nervous system (CNS), the intestine and the gut microbiota, known as "microbiota-gut-brain axis", has been hypothesized to play a pivotal role in maintaining central and peripheral functions, as well as mental health. Thus, dysbiosis with specific microbiota imbalances seems to be strongly associated with the onset psychiatric disorders by altering neurodevelopment, enhancing neurodegeneration, affecting behaviour and mood. Fecal microbiota transplantation (FMT) consists of transferring the fecal matter from a donor into the gastrointestinal tract of a recipient, and it is used to quickly modulate the gut microbiota. This review focuses on the uses of FMT in psychiatric disorders. FMT has been used to induce dysbiosis and to study the disease development, or to heal dysbiosis-related mental disorders. Overall, FMT of impaired microbiota resulted effective in enhancing psychiatric-like disturbances (mainly depression and anxiety) in recipient animals, plausibly by impairing immune system, inflammatory and metabolic pathways, neurochemical processes and neuro-transmission. On the other side, preclinical and clinical data suggest that reversing or mitigating dysbiosis seems a promising strategy to restore behavioural impairments or to obtain psychiatric symptom relief. However, current evidence is limited by the lack of procedural standardization, the paucity of human studies in the vastity of psychiatric conditions and the need of a microbiota-targeted donor-recipient matching.}, }
@article {pmid33496893, year = {2021}, author = {Tariq, R and Hayat, M and Pardi, D and Khanna, S}, title = {Predictors of failure after fecal microbiota transplantation for recurrent Clostridioides difficile infection: a systematic review and meta-analysis.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {40}, number = {7}, pages = {1383-1392}, pmid = {33496893}, issn = {1435-4373}, abstract = {Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection (CDI), with ~15% 1-year recurrence rate. Small studies have identified variable risk factors associated with FMT failure. We, therefore, performed a systematic review and meta-analysis to evaluate the predictors of FMT failure. A systematic search of Medline, Embase, and Web of Science was performed from January 2013 up to June 2020. Meta-analyses were performed using random-effects models and pooled adjusted odds ratios for risk factors reported in ≥2 studies were calculated. Overall, 2671 patients with recurrent CDI who underwent FMT in 12 studies were included. FMT failure occurred in 454 patients (16.9%) with median follow-up of 3 months (range 2-7.7 months). A total of 9 risk factors were identified in ≥2 studies. Meta-analysis showed that use of non- CDI antibiotics, presence of inflammatory bowel disease, poor quality of bowel preparation, CDI-related hospitalization before FMT, inpatient FMT, and severe CDI were associated with statistically significant increased risk of failure after FMT. Increasing age, female gender, and immunocompromised status were not associated with increased risk for FMT failure. Several risk factors (both modifiable and non-modifiable) are associated with FMT failure. Lower use of antibiotics in the post-FMT period and good bowel preparation at the time of FMT are associated with lower risk of failure after FMT. Additionally, patients with non-modifiable risk factors should be counseled to be particularly alert about recurrent symptoms after FMT.}, }
@article {pmid33483999, year = {2021}, author = {Marrs, T and Walter, J}, title = {Pros and cons: Is faecal microbiota transplantation a safe and efficient treatment option for gut dysbiosis?.}, journal = {Allergy}, volume = {76}, number = {7}, pages = {2312-2317}, doi = {10.1111/all.14750}, pmid = {33483999}, issn = {1398-9995}, mesh = {*Clostridium Infections/therapy ; Dysbiosis/therapy ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {Faecal Microbiota Transplantation (FMT) is well established as an effective treatment for Clostridioides difficile infection (CDI), restoring gut microbiome diversity and function. The utility of FMT is currently being explored in relation to other immune-mediated pathologies, such as allergic disease, inflammatory bowel diseases and autoimmune diseases. Clinical trials in these areas are ongoing, and the altered gut microbiota (dysbiosis) that is often observed in these pathologies provides a rationale for the application of FMT to restore the microbiome. However, there is controversy on the risk-benefit ratio as it relates to the use of FMTs in pathologies other than CDI. In this Pro and Con article, we present the arguments for and against the use of FMT in immune-mediated pathologies, such as allergic disease. We further identify research gaps and recommend how these may be addressed in future studies.}, }
@article {pmid33483370, year = {2021}, author = {Di Modica, M and Gargari, G and Regondi, V and Bonizzi, A and Arioli, S and Belmonte, B and De Cecco, L and Fasano, E and Bianchi, F and Bertolotti, A and Tripodo, C and Villani, L and Corsi, F and Guglielmetti, S and Balsari, A and Triulzi, T and Tagliabue, E}, title = {Gut Microbiota Condition the Therapeutic Efficacy of Trastuzumab in HER2-Positive Breast Cancer.}, journal = {Cancer research}, volume = {81}, number = {8}, pages = {2195-2206}, doi = {10.1158/0008-5472.CAN-20-1659}, pmid = {33483370}, issn = {1538-7445}, abstract = {Emerging evidence indicates that gut microbiota affect the response to anticancer therapies by modulating the host immune system. In this study, we investigated the impact of gut microbiota on immune-mediated trastuzumab antitumor efficacy in preclinical models of HER2-positive breast cancer and in 24 patients with primary HER2-positive breast cancer undergoing trastuzumab-containing neoadjuvant treatment. In mice, the antitumor activity of trastuzumab was impaired by antibiotic administration or fecal microbiota transplantation from antibiotic-treated donors. Modulation of the intestinal microbiota was reflected in tumors by impaired recruitment of CD4+ T cells and granzyme B-positive cells after trastuzumab treatment. Antibiotics caused reductions in dendritic cell (DC) activation and the release of IL12p70 upon trastuzumab treatment, a mechanism that was necessary for trastuzumab effectiveness in our model. In patients, lower α-diversity and lower abundance of Lachnospiraceae, Turicibacteraceae, Bifidobacteriaceae, and Prevotellaceae characterized nonresponsive patients (NR) compared with those who achieved pathologic complete response (R), similar to antibiotic-treated mice. The transfer of fecal microbiota from R and NR into mice bearing HER2-positive breast cancer recapitulated the response to trastuzumab observed in patients. Fecal microbiota β-diversity segregated patients according to response and positively correlated with immune signature related to interferon (IFN) and NO2-IL12 as well as activated CD4+ T cells and activated DCs in tumors. Overall, our data reveal the direct involvement of the gut microbiota in trastuzumab efficacy, suggesting that manipulation of the gut microbiota is an optimal future strategy to achieve a therapeutic effect or to exploit its potential as a biomarker for treatment response. SIGNIFICANCE: Evidence of gut microbiota involvement in trastuzumab efficacy represents the foundation for new therapeutic strategies aimed at manipulating commensal bacteria to improve response in trastuzumab-resistant patients.See related commentary by Sharma, p. 1937 GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/8/2195/F1.large.jpg.}, }
@article {pmid33483079, year = {2021}, author = {Sang, T and Guo, C and Guo, D and Wu, J and Wang, Y and Wang, Y and Chen, J and Chen, C and Wu, K and Na, K and Li, K and Fang, L and Guo, C and Wang, X}, title = {Suppression of obesity and inflammation by polysaccharide from sporoderm-broken spore of Ganoderma lucidum via gut microbiota regulation.}, journal = {Carbohydrate polymers}, volume = {256}, number = {}, pages = {117594}, doi = {10.1016/j.carbpol.2020.117594}, pmid = {33483079}, issn = {1879-1344}, mesh = {Animals ; Body Weight ; Computational Biology ; Diet, High-Fat ; Dysbiosis ; Endotoxemia/metabolism ; Feces/microbiology ; Ganoderma/*drug effects ; *Gastrointestinal Microbiome ; Glucose Tolerance Test ; Hyperlipidemias/drug therapy/metabolism ; Inflammation/*drug therapy/metabolism ; Macrophages/cytology ; Male ; Mice ; Mice, Inbred C57BL ; Obesity/*drug therapy/metabolism ; Polysaccharides/*chemistry ; Powders ; RNA, Ribosomal, 16S/metabolism ; Spores, Fungal ; }, abstract = {Ganoderma lucidum has been shown to have anti-obesity effects. However, polysaccharide extracted from the sporoderm-broken spores of Ganoderma lucidum (BSGLP) against obesity and its underlying mechanisms have never been reported. In the current study, we showed that BSGLP inhibited high-fat diet (HFD)-induced obesity, hyperlipidemia, inflammation, and fat accumulation in C57BL/6 J mice. BSGLP improved HFD-induced gut microbiota dysbiosis, maintained intestinal barrier function, increased short-chain fatty acids production and GPR43 expression, ameliorated endotoxemia, manifested by reduced serum lipopolysaccharide level, and increased ileum expression of tight junction proteins and antimicrobial peptides. Fecal microbiota transplantation study confirmed that BSGLP-induced microbiota change is responsible, at least in part, for obesity inhibition. Besides, BSGLP notably alleviated HFD-induced upregulation of TLR4/Myd88/NF-κB signaling pathway in adipose tissue. Collectively, our study showed for the first time that BSGLP might be used as a prebiotic agent to inhibit obesity and hyperlipidemia through modulating inflammation, gut microbiota, and gut barrier function.}, }
@article {pmid33482620, year = {2021}, author = {Nejadghaderi, SA and Nazemalhosseini-Mojarad, E and Asadzadeh Aghdaei, H}, title = {Fecal microbiota transplantation for COVID-19; a potential emerging treatment strategy.}, journal = {Medical hypotheses}, volume = {147}, number = {}, pages = {110476}, doi = {10.1016/j.mehy.2020.110476}, pmid = {33482620}, issn = {1532-2777}, mesh = {Bacteria/classification ; COVID-19/*therapy/virology ; China ; Cost-Benefit Analysis ; *Fecal Microbiota Transplantation ; Feces/virology ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology/*virology ; Humans ; Immune System ; Lung/microbiology ; Models, Theoretical ; }, abstract = {At the end of 2019, an emerging outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that first reported from Wuhan, China. The first manifestations of patients infected with SARS-CoV-2 was flu-like symptoms, while other type of manifestations, especially gastrointestinal manifestations were discovered recently. As of June 2020, there is no specific drug or treatment strategy for COVID-19, a disease caused by SARS-CoV-2, so different combination of antiviral drugs is currently being used. Gut microbiota mostly consists of four phyla, including Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. The interaction between gut microbiota and immune system through releasing some cytokines such as IL-1β, IL-2, IL-10, TNF-α, and IFN-γ that play roles in the severity of COVID-19. In this article, a new potential treatment for COVID-19 by fecal microbiota transplantation (FMT) is described. FMT revealed promising results in different diseases, especially recurrent clostridium difficile infection, and it might reduce length of hospital admission and severity of the disease by modification of gut microbiota composition.}, }
@article {pmid33477939, year = {2021}, author = {Burz, SD and Monnoye, M and Philippe, C and Farin, W and Ratziu, V and Strozzi, F and Paillarse, JM and Chêne, L and Blottière, HM and Gérard, P}, title = {Fecal Microbiota Transplant from Human to Mice Gives Insights into the Role of the Gut Microbiota in Non-Alcoholic Fatty Liver Disease (NAFLD).}, journal = {Microorganisms}, volume = {9}, number = {1}, pages = {}, pmid = {33477939}, issn = {2076-2607}, support = {ANR-15-CE14-0021-03//Agence Nationale de la Recherche/ ; }, abstract = {Non-alcoholic fatty liver diseases (NAFLD) are associated with changes in the composition and metabolic activities of the gut microbiota. However, the causal role played by the gut microbiota in individual susceptibility to NAFLD and particularly at its early stage is still unclear. In this context, we transplanted the microbiota from a patient with fatty liver (NAFL) and from a healthy individual to two groups of mice. We first showed that the microbiota composition in recipient mice resembled the microbiota composition of their respective human donor. Following administration of a high-fructose, high-fat diet, mice that received the human NAFL microbiota (NAFLR) gained more weight and had a higher liver triglycerides level and higher plasma LDL cholesterol than mice that received the human healthy microbiota (HR). Metabolomic analyses revealed that it was associated with lower and higher plasma levels of glycine and 3-Indolepropionic acid in NAFLR mice, respectively. Moreover, several bacterial genera and OTUs were identified as differently represented in the NAFLR and HR microbiota and therefore potentially responsible for the different phenotypes observed. Altogether, our results confirm that the gut bacteria play a role in obesity and steatosis development and that targeting the gut microbiota may be a preventive or therapeutic strategy in NAFLD management.}, }
@article {pmid33477417, year = {2021}, author = {Hassouneh, R and Bajaj, JS}, title = {Gut Microbiota Modulation and Fecal Transplantation: An Overview on Innovative Strategies for Hepatic Encephalopathy Treatment.}, journal = {Journal of clinical medicine}, volume = {10}, number = {2}, pages = {}, pmid = {33477417}, issn = {2077-0383}, support = {2I0CX001076//Office of Research and Development/ ; R21TR002024/TR/NCATS NIH HHS/United States ; R21TR003095/TR/NCATS NIH HHS/United States ; }, abstract = {Hepatic encephalopathy (HE) is a major complication of cirrhosis, which is associated with gut microbial composition and functional alterations. Current treatments largely focus on gut microbiota using lactulose, rifaximin and other agents. However, despite these treatments, patients with HE have a high rate of readmission, morbidity and cognitive impairment. Fecal microbiota transplant (FMT) involves introduction of a donor microbiota into a recipient and is currently mainly used for recurrent C. difficile infection (rCDI). The role of FMT in cirrhosis and HE is evolving. There have been two randomized clinical trials (RCT) and several case reports/series in cirrhosis. Both RCTs were safety-focused phase 1 trials. One involved pre-FMT antibiotics and FMT enema versus standard of care, while the other involved 15 FMT capsules versus placebo without pre-FMT antibiotics. There was evidence of safety in both trials and the FMT group demonstrated reduction in hospitalizations compared to the non-FMT group. Changes in microbial function centered around short-chain fatty acids, bile acids and brain function showed improvement in the FMT groups. Long-term follow-up demonstrated continued safety and reduction in the antibiotic-resistance gene carriage. However, larger trials of FMT in HE are needed that can refine the dose, duration and route of FMT administration.}, }
@article {pmid33476924, year = {2021}, author = {Wang, J and Ishfaq, M and Li, J}, title = {Lactobacillus salivarius ameliorated Mycoplasma gallisepticum-induced inflammatory injury and secondary Escherichia coli infection in chickens: Involvement of intestinal microbiota.}, journal = {Veterinary immunology and immunopathology}, volume = {233}, number = {}, pages = {110192}, doi = {10.1016/j.vetimm.2021.110192}, pmid = {33476924}, issn = {1873-2534}, mesh = {Animals ; *Chickens ; Chromatin Immunoprecipitation/veterinary ; Disease Susceptibility ; Escherichia coli Infections/etiology/microbiology/prevention &amp; control/*veterinary ; *Gastrointestinal Microbiome ; Inflammation/immunology/prevention &amp; control/veterinary ; Lactobacillus salivarius/*physiology ; Lung Diseases/microbiology/prevention &amp; control/veterinary ; Macrophages, Peritoneal/immunology ; Mycoplasma Infections/complications/microbiology/therapy/*veterinary ; *Mycoplasma gallisepticum ; Poultry Diseases/microbiology/*prevention &amp; control ; }, abstract = {Mycoplasma gallisepticum (MG) infection alone or in combination with other pathogens have brought huge economic losses to the poultry industry. The intestinal microbiota plays a critical role in host defence against respiratory infection. To explore the role of intestinal microbiota in MG-induced inflammation-mediated lung injury and secondary Escherichia coli infection, MG infection model and fecal microbiota transplantation model were developed. The results showed that MG infection changed gut microbiota composition along with lung inflammation injury. Fecal microbiota transplantation from chickens infected with MG to antibiotics cocktail treated chickens decreased host defense against Escherichia coli due to impaired intestinal mucosal barrier, downregulated the mRNA expression levels of host defense enzymes and blocked autophagic flux. Lactobacillus salivarius intake alleviated lung inflammation injury caused by MG infection and increased host defense against Escherichia coli by improved gut microbiota composition. These results highlighted the role of gut microbiota in MG-infection induced lung inflammation injury and secondary infection that offered a new strategy for preventive intervention against MG infection.}, }
@article {pmid33476379, year = {2021}, author = {Rupawala, AH and Gachette, D and Bakhit, M and Jimoh, L and Kelly, CR}, title = {Management of Severe and Severe/Complicated Clostridoides difficile Infection using Sequential Fecal Microbiota Transplant by Retention Enema.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciab041}, pmid = {33476379}, issn = {1537-6591}, abstract = {We evaluated serial FMT by retention enema in patients with severe or severe/complicated CDI unresponsive to at least 48 hours of standard antibiotic therapy. Of the 15 patients included, despite initial improvement in most patients, only 5 patients sustained cure at 30 days and serious adverse events occurred in 4 patients.}, }
@article {pmid33471490, year = {2021}, author = {Du, C and Luo, Y and Walsh, S and Grinspan, A}, title = {Oral Fecal Microbiota Transplant Capsules Are Safe and Effective for Recurrent Clostridioides difficile Infection: A Systematic Review and Meta-Analysis.}, journal = {Journal of clinical gastroenterology}, volume = {55}, number = {4}, pages = {300-308}, pmid = {33471490}, issn = {1539-2031}, mesh = {Capsules ; Clostridioides ; *Clostridium Infections/therapy ; *Fecal Microbiota Transplantation/adverse effects ; Humans ; Neoplasm Recurrence, Local ; Randomized Controlled Trials as Topic ; Recurrence ; Treatment Outcome ; }, abstract = {GOALS: We performed a systematic review with meta-analysis to examine the efficacy and safety of oral fecal microbiota transplantation (FMT) capsules for recurrent Clostridioides difficile infection (rCDI).<br><br>BACKGROUND: FMT through colonoscopy is established as effective and safe in treating multiple recurrences of CDI, but consensus has not been established on delivery through oral capsules.<br><br>STUDY: A systematic literature search was performed with multiple databases including MEDLINE and EMBASE to identify original studies including at least 10 patients that investigated the role of oral FMT capsules to treat rCDI. Cure rates were pooled by a random effects model and publication bias was assessed with the Egger test. Secondary analyses assessed for differences between capsule preparation (frozen vs. lyophilized stool) and delivery modality (capsule vs. colonoscopy).<br><br>RESULTS: Fifteen studies (12 case series and 3 randomized controlled trials) encompassing 763 patients were identified for inclusion. Significant variability existed in baseline patient characteristics and protocols. Meta-analysis of proportions showed efficacy of oral FMT capsules to be 0.821 (95% confidence interval: 0.762-0.874). No evidence for publication bias was found (P=0.51). Secondary analyses did not find significant differences in efficacy. Fourteen adverse events leading to death or hospitalization were noted, none of which were attributed to FMT.<br><br>CONCLUSIONS: Oral FMT capsules for rCDI are promising because of ease of administration and noninvasive delivery. We found an overall efficacy of 82.1% with a low rate of serious adverse events. Further studies are needed to optimize protocols and outcomes.}, }
@article {pmid33468164, year = {2021}, author = {Fang, H and Fu, L and Li, X and Lu, C and Su, Y and Xiong, K and Zhang, L}, title = {Long-term efficacy and safety of monotherapy with a single fresh fecal microbiota transplant for recurrent active ulcerative colitis: a prospective randomized pilot study.}, journal = {Microbial cell factories}, volume = {20}, number = {1}, pages = {18}, pmid = {33468164}, issn = {1475-2859}, support = {No. 1408085MH178//Natural Science Foundation of Anhui Province/ ; }, abstract = {BACKGROUND: To assess the long-term safety and efficacy of monotherapy with a single fresh fecal microbiota transplant (FMT) for recurrent ulcerative colitis (UC).<br><br>RESULTS: Twenty-six eligible patients were enrolled, and 6 patients were excluded. Ultimately, 20 patients were randomized to the FMT group (n = 10) and the control group (n = 10); 80% were females (F/M = 16/4), the mean age was 48 ± 14 years, and the mean duration was 6.4 ± 8.2 years. The mean length of post-FMT follow-up was 19.1 ± 10.1 months (6-38). No statistically significant differences in baseline demographic or clinical characteristics were found between the groups. Ninety percent of patients in the FMT group and 50% of patients in the control group met the primary endpoint at week 8. The Mayo score was significantly decreased compared with that of the control group (n = 10) when reassessed at week 4 (P = 0.001) and week 8 (P = 0.019) after FMT; there was no significant difference 6 months after treatment. The median remission time was 24 months (95% CI 68.26-131.7%) in both the FMT (range 6-38 months) and control groups (range 7-35 months), with no significant difference (P = 0.895). Participants tolerated FMT treatment, and no adverse events occurred during long-term follow-up, with one treatment-related significant adverse event (EBV infection) occurring within 2 weeks after FMT. Stool microbiota composition analysis indicated improved gut microbiota diversity after FMT, with expansion of stool-donor taxa. Bacteroidetes, Firmicutes and Proteobacteria were the dominant bacterial phyla of the gut microbiota in active UC patients. The relative abundance of Bacteroidetes decreased and that of Proteobacteria increased significantly in active UC patients compared with donors, while Firmicutes showed no significant changes. A single fresh FMT could effectively reconstruct the gut microbiota composition in patients with active UC and maintain stability, with increased Bacteroidetes and decreased Proteobacteria abundance. FMT significantly reduced the relative abundance of Escherichia and increased the relative abundance of Prevotella at the genus level. Pyruvate metabolism, glyoxylate and dicarboxylate metabolism, and pantothenate and CoA biosynthesis showed significant differences after transplantation.<br><br>CONCLUSIONS: Monotherapy with a single fresh FMT is an effective and safe strategy to induce long-term remission without drugs in patients with active UC and may be an alternative induction therapy for recu