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Bibliography on: Fecal Transplantation

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Robert J. Robbins is a biologist, an educator, a science administrator, a publisher, an information technologist, and an IT leader and manager who specializes in advancing biomedical knowledge and supporting education through the application of information technology. More About:  RJR | OUR TEAM | OUR SERVICES | THIS WEBSITE

RJR: Recommended Bibliography 29 Sep 2022 at 02:00 Created: 

Fecal Transplantation

Fecal Transplantion is a procedure in which fecal matter is collected from a tested donor, mixed with a saline or other solution, strained, and placed in a patient, by colonoscopy, endoscopy, sigmoidoscopy, or enema. The theory behind the procedure is that a normal gut microbial ecosystem is required for good health and that sometimes a benefucuial ecosystem can be destroyed, perhaps by antibiotics, allowing other bacteria, specifically Clostridium difficile to over-populate the colon, causing debilitating, sometimes fatal diarrhea. C. diff. is on the rise throughout the world. The CDC reports that approximately 347,000 people in the U.S. alone were diagnosed with this infection in 2012. Of those, at least 14,000 died. Fecal transplant has also had promising results with many other digestive or auto-immune diseases, including Irritable Bowel Syndrome, Crohn's Disease, and Ulcerative Colitis. It has also been used around the world to treat other conditions, although more research in other areas is needed. Fecal transplant was first documented in 4th century China, where the treatment was known as yellow soup.

Created with PubMed® Query: "(fecal OR faecal) (transplant OR transplantation)" OR "fecal microbiota transplant" NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

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RevDate: 2022-09-28

Ramesh AS, Munoz Tello C, Jamil D, et al (2022)

Role of Fecal Microbiota Transplantation in Reducing Clostridioides difficile Infection-Associated Morbidity and Mortality: A Systematic Review.

Cureus, 14(8):e28402.

Clostridioides difficile (C. difficile) is a gram-positive, anaerobic, spore-forming bacterium that produces toxins A and B, disrupting the intestinal brush border and resulting in severe diarrhea. The most common causes of infection include prolonged antibiotic use, proton pump inhibitors (PPIs), and long-term hospitalization resulting in complications such as pseudomembranous colitis and toxic megacolon. This systematic review aims to consider fecal microbiota transplantation (FMT) as an early treatment modality in C. difficile infection to prevent complications and reduce related morbidity and mortality. We systematically screened three databases using regular keywords such as "fecal microbiota transplantation," "C. difficile," "pseudomembranous colitis," and "toxic megacolon" and Medical Subject Headings (MeSH) terms. We applied the inclusion and exclusion criteria and performed a thorough quality appraisal using standardized checklists. We were finally left with 10 articles, including seven case reports, one case series, and two observational studies. Questions remain as to the route of administration of FMT, timing, safety, availability, and the number of sittings required. More randomized controlled trials are needed to address all these questions and to assess the safety of FMT. We believe the role of FMT is very important as it can prevent C. difficile related complications and would be an ideal treatment option in a population group that is often unfit for surgical management.

RevDate: 2022-09-28

Qiao X, Biliński J, Wang L, et al (2022)

Safety and efficacy of fecal microbiota transplantation in the treatment of graft-versus-host disease.

Bone marrow transplantation [Epub ahead of print].

This article evaluates the efficacy and safety of FMT in the treatment of GVHD after HSCT using a systematic literature search to conduct a meta-analysis constructed of studies involving GVHD patients treated with FMT. 23 studies were included, among which 2 prospective cohort studies, 10 prospective single arm studies, 2 retrospective single arm studies, 2 case series and 7 case reports, comprise a total of 242 patients with steroid-resistant or steroid-dependent GVHD secondary to HSCT who were treated with FMT. 100 cases achieved complete responses, while 61 cases showed partial responses, and 81 cases presented no effect after FMT treatment. The estimate of clinical remission odds ratio was 5.51 (95% CI 1.49-20.35) in cohort studies, and the pooled clinical remission rate is 64% (51-77%) in prospective single arm studies and 81% (62-95%) in retrospective studies, case series and case reports. Five (2.1%) patients had FMT-related infection events, but all recovered after treatment. Other adverse effects were mild and acceptable. Microbiota diversity and composition, donor type, and other related issues were also analyzed. The data proves that FMT is a promising treatment modality of GVHD, but further validation of its safety and efficacy is still needed with prospective control studies.Clinical trial registration: Registered in https://www.crd.york.ac.uk/PROSPERO/ CRD42022296288.

RevDate: 2022-09-27

Hooi SL, Dwiyanto J, Rasiti H, et al (2022)

A case report of improvement on ADHD symptoms after fecal microbiota transplantation with gut microbiome profiling pre- and post-procedure.

Current medical research and opinion [Epub ahead of print].

BACKGROUND: Recent studies demonstrate the association of the gut microbiome in regulating interactions between the central nervous system and intestinal function. Individuals with ADHD have been shown to have unique gut microbial signature, with depletion of beneficial commensal microbes. Fecal microbiota transplant (FMT) restores the imbalanced gut microbiome and may replete missing microbes to increase production of hormones and neurotransmitters regulating human behavior and cognition.

RESEARCH DESIGN & METHODS: Here, we present an interesting case of a 22-year-old woman treated with FMT primarily to treat recurrent Clostridioides difficile infection, which coincidentally alleviated her ADHD symptoms. We also present the pre- and post-FMT gut microbiota profiles conducted using shotgun metagenomic sequencing on the patient's fecal samples to thereby highlight potential microbial-associated mechanisms associated with the relief of ADHD symptoms.

RESULTS & CONCLUSIONS: Our case report provides preliminary evidence regarding the use of FMT in a patient with Clostridioides difficile and ADHD. We speculate that gut microbiome modulation, in particular the gain or loss of specific microbial species and pathways involving the metabolism of SCFAs, tryptophan and GABA, may merit further exploration as a potential therapeutic strategy for ADHD.

RevDate: 2022-09-28

Pasokh A, Farzipour M, Mahmoudi J, et al (2022)

The effect of fecal microbiota transplantation on stroke outcomes: A systematic review.

Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association, 31(11):106727 pii:S1052-3057(22)00421-9 [Epub ahead of print].

BACKGROUND AND PURPOSE: Fecal microbiota transplantation (FMT) is a novel microbiota-based therapeutic method that transfers stool from donor into a recipient and its application is under investigating for neurological disorders such as stroke. In this systematic review, we assessed the effect of FMT in progression and treatment of stroke and recovery of post-stroke complications.

METHODS: Preliminary studies were searched in MEDLINE via PubMed, Scopus, COCHRANE library and Google Scholar, databases up to February 2022. The search strategy was restricted to articles about FMT in stroke. The initial search yielded 4570 articles, of which 19 publications were included in our systematic review.

RESULTS: Based on outcomes transferring microbiome from healthy or ischemic donor to other ischemic recipient can affect brain infarct volume and survival rate, neurological and behavioral outcomes, and inflammatory pathways.

CONCLUSIONS: Our systematic review on preclinical studies showed that manipulating gut microbiota via FMT can be a possible therapeutic approach for treatment of stroke and recovery of post-stroke complications.

RevDate: 2022-09-28

Gill VJS, Soni S, Shringarpure M, et al (2022)

Gut Microbiota Interventions for the Management of Obesity: A Literature Review.

Cureus, 14(9):e29317.

The gut microbiota (GM) has been recognized as an important factor in the development of metabolic diseases such as obesity; it has been reported that the composition of the GM differs in obese and lean subjects, suggesting that microbiota dysbiosis can contribute to changes in body weight. Dysbiosis occurs due to an imbalance in the composition of gut bacteria, changes in the metabolic process, or changes in the distribution of microbiota within the gut. Dysbiosis can change the functioning of the intestinal barrier and the gut-associated lymphoid tissues (GALT). Microbial manipulation may help with preventing or treating weight gain and associated comorbidities. Approaches to this may range from dietary manipulation, which is suitable to treat the individual's microflora, to probiotics, prebiotics, synbiotics, and fecal microbiota transplant (FMT).

RevDate: 2022-09-28
CmpDate: 2022-09-28

Li YG, Yu ZJ, Li A, et al (2022)

Gut microbiota alteration and modulation in hepatitis B virus-related fibrosis and complications: Molecular mechanisms and therapeutic inventions.

World journal of gastroenterology, 28(28):3555-3572.

Hepatitis B virus (HBV) has posed a threat to public health, mainly resulting in liver damage. With long-term accumulation of extracellular matrix, patients with chronic hepatitis B are at high risk of developing into liver fibrosis and cirrhosis and even life-threatening hepatic carcinoma. The occurrence of complications such as spontaneous bacterial peritonitis and hepatic encephalopathy greatly increases disability and mortality. With deeper understanding of the bidirectional interaction between the liver and the gut (gut-liver axis), there is a growing consensus that the human health closely relates to the gut microbiota. Supported by animal and human studies, the gut microbiota alters as the HBV-related liver fibrosis initials and progresses, characterized as the decrease of the ratio between "good" and "potentially pathogenic" microbes. When the primary disease is controlled via antiviral treatment, the gut microbiota dysfunction tends to be improved. Conversely, the recovery of gut microbiota can promote the regression of liver fibrosis. Therapeutic strategies targeted on gut microbiota (rifaximin, probiotics, engineered probiotics and fecal microbiota transplantation) have been applied to animal models and patients, obtaining satisfactory results.

RevDate: 2022-09-28

Ma J, Chen S, Li Y, et al (2022)

Arbutin improves gut development and serum lipids via Lactobacillus intestinalis.

Frontiers in nutrition, 9:948573.

Arbutin has been widely studied in whitening, anti-inflammatory, and antioxidant. However, the interaction between arbutin and intestinal microbes has been rarely studied. Thus, mice were treated with arbutin concentrations of 0, 0.1, 0.2, 0.4, and 1 mg/ml. We found that arbutin promoted gut development such as villus length, villus areas, and villus length/crypt depth (L/D). Total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were significantly reduced by low concentrations of arbutin. Importantly, we analyzed the microbial composition in the control and 0.4 mg/ml arbutin group and found that the abundance of Lactobacillus intestinalis (L. intestinalis) was highest and enhanced in arbutin. Further, mice were fed with oral antibiotics and antibiotics + 0.4 mg/ml arbutin and then we transplanted fecal microbes from oral 0.4 mg/ml arbutin mice to mice pretreated with antibiotics. Our results showed that arbutin improves gut development, such as villus width, villus length, L/D, and villus areas. In addition, L. intestinalis monocolonization was carried out after a week of oral antibiotics and increased villus length, crypt depth, and villus areas. Finally, in vitro arbutin and L. intestinalis co-culture showed that arbutin promoted the growth and proliferation of L. intestinalis. Taken together, our results suggest that arbutin improves gut development and health of L. intestinalis. Future studies are needed to explore the function and mechanism of L. intestinalis affecting gut development.

RevDate: 2022-09-28
CmpDate: 2022-09-28

Ikeda Y, Taniguchi K, Sawamura H, et al (2022)

Promising role of D-amino acids in irritable bowel syndrome.

World journal of gastroenterology, 28(31):4471-4474.

Irritable bowel syndrome (IBS) is an important health care concern. Alterations in the microbiota of the gut-brain axis may be linked to the pathophysiology of IBS. Some dietary intake could contribute to produce various metabolites including D-amino acids by the fermentation by the gut microbiota. D-amino acids are the enantiomeric counterparts of L-amino acids, in general, which could play key roles in cellular physiological processes against various oxidative stresses. Therefore, the presence of D-amino acids has been shown to be linked to the protection of several organs in the body. In particular, the gut microbiota could play significant roles in the stability of emotion via the action of D-amino acids. Here, we would like to shed light on the roles of D-amino acids, which could be used for the treatment of IBS.

RevDate: 2022-09-28

Spanu D, Pretta A, Lai E, et al (2022)

Hepatocellular carcinoma and microbiota: Implications for clinical management and treatment.

World journal of hepatology, 14(7):1319-1332.

Gut microbiota plays an essential role in host homeostasis. It is involved in several physiological processes such as nutrients digestion and absorption, maintenance of intestinal epithelial barrier integrity and immune system self-tolerance. Especially the gut microbiota is assumed to play a crucial role in many gastrointestinal, pancreatic and liver disorders. Its role in hepatic carcinogenesis is also gaining increasing interest, especially regarding the development of therapeutic strategies. Different studies are highlighting a link between some bacterial strains and liver disease, including hepatocellular carcinoma (HCC). Indeed, HCC represents an interesting field of research in this perspective, due to the gut-liver axis, to the implication of microbiota in the immune system and to the increasing number of immunotherapy agents investigated in this tumour. Thus, the assessment of the role of microbiota in influencing clinical outcome for patients treated with these drugs is becoming of increasing importance. Our review aims to give an overview on the relationship between microbiota and HCC development/progression and treatment. We focus on potential implications on the available treatment strategies and those under study in the various stages of disease. We highlight the pathogenic mechanisms and investigate the underlying molecular pathways involved. Moreover, we investigate the potential prognostic and/or predictive role of microbiota for target therapies, immune checkpoint inhibitors and loco-regional treatment. Finally, given the limitation of current treatments, we analyze the gut microbiota-mediated therapies and its potential options for HCC treatment focusing on fecal microbiota transplantation.

RevDate: 2022-09-28

Nishida A, Nishino K, Ohno M, et al (2022)

Update on gut microbiota in gastrointestinal diseases.

World journal of clinical cases, 10(22):7653-7664.

The human gut is a complex microbial ecosystem comprising approximately 100 trillion microbes collectively known as the "gut microbiota". At a rough estimate, the human gut microbiome contains almost 3.3 million genes, which are about 150 times more than the total human genes present in the human genome. The vast amount of genetic information produces various enzymes and physiologically active substances. Thus, the gut microbiota contributes to the maintenance of host health; however, when healthy microbial composition is perturbed, a condition termed "dysbiosis", the altered gut microbiota can trigger the development of various gastrointestinal diseases. The gut microbiota has consequently become an extremely important research area in gastroenterology. It is also expected that the results of research into the gut microbiota will be applied to the prevention and treatment of human gastrointestinal diseases. A randomized controlled trial conducted by a Dutch research group in 2013 showed the positive effect of fecal microbiota transplantation (FMT) on recurrent Clostridioides difficile infection (CDI). These findings have led to the development of treatments targeting the gut microbiota, such as probiotics and FMT for inflammatory bowel diseases (IBD) and other diseases. This review focuses on the association of the gut microbiota with human gastrointestinal diseases, including CDI, IBD, and irritable bowel syndrome. We also summarize the therapeutic options for targeting the altered gut microbiota, such as probiotics and FMT.

RevDate: 2022-09-28

Philips CA, Schnabl B, JS Bajaj (2022)

Gut Microbiome and Alcohol-associated Liver Disease.

Journal of clinical and experimental hepatology, 12(5):1349-1359.

Changes in gut microbiota (GM) may be associated with the causation and progression of multiple liver diseases such as metabolic-associated liver disease, alcohol-associated liver disease (ALD), alcohol-associated hepatitis (AH), primary biliary cholangitis, primary sclerosing cholangitis, autoimmune liver disease, and most importantly, complications of cirrhosis and portal hypertension such as hepatic encephalopathy (HE), infection, and hepatocellular carcinoma. ALD includes simple steatosis, steatohepatitis, AH, cirrhosis, and acute-on-chronic liver failure. Alcohol consumption is associated with GM changes even before ALD development, and continued alcohol intake results in progressive dysbiosis and development of clinical events such as AH, infection, and HE. The composition and function of GM, specific changes in bacterial communities, and the functional metabolism of GM are affected in the spectrum of ALD, as revealed using high-throughput sequencing. It was reported in preliminary studies that modulation of disrupted GM improves adverse clinical events and ameliorates disease progression in ALD. In this review, we exhaustively discuss the preclinical and clinical studies on GM in ALD and critically discuss GM modulation and its effects based on various human and animal models of ALD.

RevDate: 2022-09-28
CmpDate: 2022-09-28

Soveral LF, Korczaguin GG, Schmidt PS, et al (2022)

Immunological mechanisms of fecal microbiota transplantation in recurrent Clostridioides difficile infection.

World journal of gastroenterology, 28(33):4762-4772.

Fecal microbiota transplantation (FMT) is a successful method for treating recurrent Clostridioides difficile (C. difficile) infection (rCDI) with around 90% efficacy. Due to the relative simplicity of this approach, it is being widely used and currently, thousands of patients have been treated with FMT worldwide. Nonetheless, the mechanisms underlying its effects are just beginning to be understood. Data indicate that FMT effectiveness is due to a combination of microbiological direct mechanisms against C. difficile, but also through indirect mechanisms including the production of microbiota-derived metabolites as secondary bile acids and short chain fatty acids. Moreover, the modulation of the strong inflammatory response triggered by C. difficile after FMT seems to rely on a pivotal role of regulatory T cells, which would be responsible for the reduction of several cells and soluble inflammatory mediators, ensuing normalization of the intestinal mucosal immune system. In this minireview, we analyze recent advances in these immunological aspects associated with the efficacy of FMT.

RevDate: 2022-09-26

Benech N, L Koppe (2022)

Is there a place for fecal microbiota transplantation in chronic kidney disease?.

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association pii:6717772 [Epub ahead of print].

RevDate: 2022-09-28

Zhai Y, Zhou W, Yan X, et al (2022)

Astragaloside IV ameliorates diet-induced hepatic steatosis in obese mice by inhibiting intestinal FXR via intestinal flora remodeling.

Phytomedicine : international journal of phytotherapy and phytopharmacology, 107:154444 pii:S0944-7113(22)00533-5 [Epub ahead of print].

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major clinical and public health burden worldwide with no established pharmacological therapy. Changes in the intestinal flora and associated metabolite bile acids (BAs) have been described in NAFLD. Astragaloside IV (AS-IV) is a low drug permeability saponin with protective effects against multiple diseases. However, the specific mechanism underlying the involvement of AS-IV in the regulation of NAFLD is yet to be clarified.

PURPOSE: This study aimed to investigate the effect of AS-IV on NAFLD and explore whether intestinal flora was involved.

METHODS: The effect of AS-IV was evaluated on high-fat diet-fed mice. Real-time PCR, immunohistochemistry, immunofluorescence, and biochemical analyses were performed. 16S rRNA gene sequencing and UPLC-TQMS were used to determine the alterations in the intestinal flora and concentration of BAs. Fecal microbiota transplantation (FMT) and intestine-specific farnesoid X receptor (FXR) knockout were also performed.

RESULTS: AS-IV treatment alleviated diet-induced metabolic impairments, particularly hepatic steatosis. These changes occurred in the setting of decreased intestinal bile salt hydrolase (BSH)-expressing flora. Further analysis showed that the reduced BSH activity increased intestinal tauro-β-muricholic acid levels, an inhibitor of intestinal FXR. Inhibition of intestinal FXR signaling by AS-IV was accompanied by decreased expression of intestinal fibroblast growth factor 15 and subsequent hepatic FXR activation as well as increased glucagon-like peptide-1 and decreased ceramide production, all of which contribute to the inhibition of sterol regulatory element-binding protein-1c-mediated hepatic steatosis. Furthermore, intestine-specific Fxr knockout and FMT further demonstrated an FXR- and intestinal flora-dependent preventive effect of AS-IV on hepatic steatosis.

CONCLUSION: These results show that the changes in intestinal flora and BAs serve an essential role in the remission of hepatic steatosis by AS-IV, thereby suggesting that AS-IV may be used as a prebiotic agent to provide viable treatment for NAFLD.

RevDate: 2022-09-26

Zoghi S, Abbasi A, Heravi FS, et al (2022)

The gut microbiota and celiac disease: Pathophysiology, current perspective and new therapeutic approaches.

Critical reviews in food science and nutrition [Epub ahead of print].

Celiac disease (CD) as a chronic gluten-sensitive intestinal condition, mainly affects genetically susceptible hosts. The primary determinants of CD have been identified as environmental and genetic variables. The development of CD is significantly influenced by environmental factors, including the gut microbiome. Therefore, gut microbiome re-programming-based therapies using probiotics, prebiotics, postbiotics, gluten-free diet, and fecal microbiota transplantation have shown promising results in the modification of the gut microbiome. Due to the importance and paucity of information regarding the CD pathophysiology, in this review, we have covered the association between CD development and gut microbiota, the effects of infectious agents, particularly the recent Covid-19 infection in CD patients, and the efficacy of potential therapeutic approaches in the CD have been discussed. Hence, scientific literature indicates that the diverse biological functions of the gut microbiota against immunomodulatory responses have made microbiome-based therapy an alternative therapeutic paradigm to ameliorate the symptoms of CD and quality of life. However, the exact potential of microbiota-based techniques that aims to quantitatively and qualitatively alter the gut microbiota to be used in the treatment and ameliorate the symptoms of CD will be determined with further research in the future.

RevDate: 2022-09-25

Najmi M, Tran T, Witt RG, et al (2022)

Modulation of the Gut Microbiome to Enhance Immunotherapy Response in Metastatic Melanoma Patients: A Clinical Review.

Dermatology and therapy [Epub ahead of print].

For patients with metastatic melanoma, immunotherapy agents represent a promising treatment option, and researchers are actively seeking to identify factors that may predict a favorable response in patients. Recent studies have elucidated possible associations between the gut microbiome and the effects of immunotherapy, where variations in the gut microbiome may influence treatment response and frequency of adverse effects. In this clinical review, we describe the current literature related to the gut microbiome in the setting of immunotherapy, and we provide an overview of interventions under investigation that may modulate the gut microbiome. These interventions include fecal microbiota transplantation, probiotics, and dietary modifications.

RevDate: 2022-09-27
CmpDate: 2022-09-26

Lavelle A, H Sokol (2022)

Understanding and predicting the efficacy of FMT.

Nature medicine, 28(9):1759-1760.

RevDate: 2022-09-28
CmpDate: 2022-09-28

Zhao Z, Ji X, Zhang T, et al (2022)

Washed microbiota transplantation improves the fertility of patients with inflammatory bowel disease.

Chinese medical journal, 135(12):1489-1491.

RevDate: 2022-09-23

Wang C, Wang Y, Yang H, et al (2022)

Uygur type 2 diabetes patient fecal microbiota transplantation disrupts blood glucose and bile acid levels by changing the ability of the intestinal flora to metabolize bile acids in C57BL/6 mice.

BMC endocrine disorders, 22(1):236.

BACKGROUND: Our epidemiological study showed that the intestinal flora of Uygur T2DM patients differed from that of normal glucose-tolerant people. However, whether the Uygur T2DM fecal microbiota transplantation could reproduce the glucose metabolism disorder and the mechanism behind has not been reported. This study was designed to explore whether Uygur T2DM fecal microbiota transplantation could reproduce the glucose metabolism disorder and its mechanism.

METHODS: The normal diet and high fat diet group consisted of C57BL/6 mice orally administered 0.2 mL sterile normal saline. For the MT (microbiota transplantation) intervention groups, C57BL/6 mice received oral 0.2 mL faecal microorganisms from Uygur T2DM. All mice were treated daily for 8 weeks and Blood glucose levels of mice were detected. Mice faecal DNA samples were sequenced and quantified using 16S rDNA gene sequencing. Then we detected the ability of the intestinal flora to metabolize bile acids (BAs) through co-culture of fecal bacteria and BAs. BA levels in plasma were determined by UPLC-MS. Further BA receptors and glucagon-like peptide-1 (GLP-1) expression levels were determined with RT-q PCR and western blotting.

RESULTS: MT impaired insulin and oral glucose tolerance. Deoxycholic acid increased and tauro-β-muricholic acid and the non-12-OH BA:12-OH BA ratio decreased in plasma. MT improved the ability of intestinal flora to produce deoxycholic acid. Besides, the vitamin D receptor in the liver and ileum and GLP-1 in the ileum decreased significantly.

CONCLUSIONS: Uygur T2DM fecal microbiota transplantation disrupts glucose metabolism by changing the ability of intestinal flora to metabolize BAs and the BAs/GLP-1 pathway.

RevDate: 2022-09-23

Ziegler S, Bereswill S, MM Heimesaat (2022)

Modulation of the intestinal microbiota impacts the efficacy of immunotherapy in cancer patients - A recent literature survey.

European journal of microbiology & immunology [Epub ahead of print].

In line with the current development of individualized cancer treatments, targeted and specialized therapeutic regimens such as immunotherapy gain importance and factors improving its efficacy come into the focus of actual research. Given the orchestrated interaction of the intestinal microbiota with host immunity the modulation of the human gut microbiota represents a therapy-enhancing factor. We therefore performed an actual literature survey on the role of the gut microbiota composition and the effects of its modification during immunotherapy of cancer patients. The included 23 studies published in the past 10 years revealed that both, distinct bacterial species and genera including Faecalibacterium prausnitzii and Bifidobacterium, respectively, enhanced distinct immunotherapy responses following PD-1/PD-L1 and CTLA-4 blockage, for instance, resulting in a better clinical outcome of cancer patients. Conversely, a high intestinal abundance of Bacteroidetes and Fusobacterium species correlated with a less efficient immunotherapy resulting in shorter progress-free survival outcomes. In conclusion, modifications of the gut microbiota by fecal microbiota transplantation or application of probiotic compounds represent potential adjunct options for immunotherapy in cancer patients which needs to be further addressed in future trials to provide individually tailored and safe adjuvant therapeutic measures in the combat of cancer.

RevDate: 2022-09-23

Chang C, Yuan X, Zhang X, et al (2022)

Gastrointestinal Microbiome and Multiple Health Outcomes: Umbrella Review.

Nutrients, 14(18): pii:nu14183726.

In recent years, there has been growing concern about the impact of the gastrointestinal microbiome on human health outcomes. To clarify the evidence for a link between the gastrointestinal microbiome and a variety of health outcomes in humans, we conducted an all-encompassing review of meta-analyses and systematic reviews that included 195 meta-analyses containing 950 unique health outcomes. The gastrointestinal microbiome is related to mortality, gastrointestinal disease, immune and metabolic outcomes, neurological and psychiatric outcomes, maternal and infant outcomes, and other outcomes. Existing interventions for intestinal microbiota (such as probiotics, fecal microbiota transplant, etc.) are generally safe and beneficial to a variety of human health outcomes, but the quality of evidence is not high, and more detailed and well-designed randomized controlled trials are necessary.

RevDate: 2022-09-23

Mazzawi T, Hausken T, Refsnes PF, et al (2022)

The Effect of Anaerobically Cultivated Human Intestinal Microbiota Compared to Fecal Microbiota Transplantation on Gut Microbiota Profile and Symptoms of Irritable Bowel Syndrome, a Double-Blind Placebo-Controlled Study.

Microorganisms, 10(9): pii:microorganisms10091819.

Fecal microbiota transplantation (FMT) from healthy donors has been shown to improve the symptoms of irritable bowel syndrome (IBS) and changes the profile of the gut microbiota for the recipients. Alternatively, anaerobically cultivated human intestinal microbiota (ACHIM) can be used to manipulate the gut microbiota. The aim of the current study was to compare the efficacy and safety of ACHIM suspension with donor-FMT and placebo (patient's own feces) to treat IBS. Out of the 62 originally included eligible patients with diarrhea-predominant IBS and their respective donors, only 43 patients completed the study by answering the questionnaires and delivering fecal samples before transplantation and after 1, 4, 12 and 24 weeks. The patients were randomized into three subgroups for receiving ACHIM suspension (n = 17), donor-FMT (n = 11), or placebo (n = 15), and were followed up for 24 weeks. Fecal samples were analyzed by sequencing 16S rRNA gene using the GA-map Dysbiosis Test (Genetic Analysis AS, Oslo, Norway). IBS symptom questionnaires improved in all three subgroups. Bacterial strain signals in IBS patients were more significant for Actinobacteria spp. and Bifidobacteria spp. after receiving donor-FMT compared to placebo and for Alistipes onderdonkii before and after treatment in the subgroups of ACHIM and donor-FMT vs. placebo. These signals change after treatment with ACHIM suspension and donor FMT towards those measured for healthy controls, but not after placebo. IBS symptom questionnaires improved in all three forms of transplantation. Some bacterial strain signals were significantly different between ACHIM and donor-FMT vs. placebo. However, the placebo subgroup failed to change the gut microbiota towards signals measured for healthy controls. The safety and efficacy of ACHIM and donor-FMT seems similar in the current study, but further larger studies are needed.

RevDate: 2022-09-23

Belvoncikova P, Maronek M, R Gardlik (2022)

Gut Dysbiosis and Fecal Microbiota Transplantation in Autoimmune Diseases.

International journal of molecular sciences, 23(18): pii:ijms231810729.

Gut microbiota dysbiosis has recently been reported in a number of clinical states, including neurological, psychiatric, cardiovascular, metabolic and autoimmune disorders. Yet, it is not completely understood how colonizing microorganisms are implicated in their pathophysiology and molecular pathways. There are a number of suggested mechanisms of how gut microbiota dysbiosis triggers or sustains extraintestinal diseases; however, none of these have been widely accepted as part of the disease pathogenesis. Recent studies have proposed that gut microbiota and its metabolites could play a pivotal role in the modulation of immune system responses and the development of autoimmunity in diseases such as rheumatoid arthritis, multiple sclerosis or type 1 diabetes. Fecal microbiota transplantation (FMT) is a valuable tool for uncovering the role of gut microbiota in the pathological processes. This review aims to summarize the current knowledge about gut microbiota dysbiosis and the potential of FMT in studying the pathogeneses and therapies of autoimmune diseases. Herein, we discuss the extraintestinal autoimmune pathologies with at least one published or ongoing FMT study in human or animal models.

RevDate: 2022-09-23

Santiso-Bellón C, Gozalbo-Rovira R, Buesa J, et al (2022)

Replication of Human Norovirus in Mice after Antibiotic-Mediated Intestinal Bacteria Depletion.

International journal of molecular sciences, 23(18): pii:ijms231810643.

Human noroviruses (HuNoVs) are the main cause of acute gastroenteritis causing more than 50,000 deaths per year. Recent evidence shows that the gut microbiota plays a key role in enteric virus infectivity. In this context, we tested whether microbiota depletion or microbiota replacement with that of human individuals susceptible to HuNoVs infection could favor viral replication in mice. Four groups of mice (n = 5) were used, including a control group and three groups that were treated with antibiotics to eliminate the autochthonous intestinal microbiota. Two of the antibiotic-treated groups received fecal microbiota transplantation from a pool of feces from infants (age 1-3 months) or an auto-transplantation with mouse feces that obtained prior antibiotic treatment. The inoculation of the different mouse groups with a HuNoVs strain (GII.4 Sydney [P16] genotype) showed that the virus replicated more efficiently in animals only treated with antibiotics but not subject to microbiota transplantation. Viral replication in animals receiving fecal microbiota from newborn infants was intermediate, whereas virus excretion in feces from auto-transplanted mice was as low as in the control mice. The analysis of the fecal microbiota by 16S rDNA NGS showed deep variations in the composition in the different mice groups. Furthermore, differences were observed in the gene expression of relevant immunological mediators, such as IL4, CXCL15, IL13, TNFα and TLR2, at the small intestine. Our results suggest that microbiota depletion eliminates bacteria that restrict HuNoVs infectivity and that the mechanism(s) could involve immune mediators.

RevDate: 2022-09-23

Yang M, Liu S, C Zhang (2022)

The Related Metabolic Diseases and Treatments of Obesity.

Healthcare (Basel, Switzerland), 10(9): pii:healthcare10091616.

Obesity is a chronic disease characterized by the abnormal or excessive accumulation of body fat, affecting more than 1 billion people worldwide. Obesity is commonly associated with other metabolic disorders, such as type 2 diabetes, non-alcoholic fatty liver disease, cardiovascular diseases, chronic kidney disease, and cancers. Factors such as a sedentary lifestyle, overnutrition, socioeconomic status, and other environmental and genetic conditions can cause obesity. Many molecules and signaling pathways are involved in the pathogenesis of obesity, such as nuclear factor (NF)-κB, Toll-like receptors (TLRs), adhesion molecules, G protein-coupled receptors (GPCRs), programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1), and sirtuin 1 (SIRT1). Commonly used strategies of obesity management and treatment include exercise and dietary change or restriction for the early stage of obesity, bariatric surgery for server obesity, and Food and Drug Administration (FDA)-approved medicines such as semaglutide and liraglutide that can be used as monotherapy or as a synergistic treatment. In addition, psychological management, especially for patients with obesity and distress, is a good option. Gut microbiota plays an important role in obesity and its comorbidities, and gut microbial reprogramming by fecal microbiota transplantation (FMT), probiotics, prebiotics, or synbiotics shows promising potential in obesity and metabolic syndrome. Many clinical trials are ongoing to evaluate the therapeutic effects of different treatments. Currently, prevention and early treatment of obesity are the best options to prevent its progression to many comorbidities.

RevDate: 2022-09-23

Štofilová J, Kvaková M, Kamlárová A, et al (2022)

Probiotic-Based Intervention in the Treatment of Ulcerative Colitis: Conventional and New Approaches.

Biomedicines, 10(9): pii:biomedicines10092236.

Although there are number of available therapies for ulcerative colitis (UC), many patients are unresponsive to these treatments or experience secondary failure during treatment. Thus, the development of new therapies or alternative strategies with minimal side effects is inevitable. Strategies targeting dysbiosis of gut microbiota have been tested in the management of UC due to the unquestionable role of gut microbiota in the etiology of UC. Advanced molecular analyses of gut microbiomes revealed evident dysbiosis in UC patients, characterized by a reduced biodiversity of commensal microbiota. Administration of conventional probiotic strains is a commonly applied approach in the management of the disease to modify the gut microbiome, improve intestinal barrier integrity and function, and maintain a balanced immune response. However, conventional probiotics do not always provide the expected health benefits to a patient. Their benefits vary significantly, depending on the type and stage of the disease and the strain and dose of the probiotics administered. Their mechanism of action is also strain-dependent. Recently, new candidates for potential next-generation probiotics have been discovered. This could bring to light new approaches in the restoration of microbiome homeostasis and in UC treatment in a targeted manner. The aim of this paper is to provide an updated review on the current options of probiotic-based therapies, highlight the effective conventional probiotic strains, and outline the future possibilities of next-generation probiotic and postbiotic supplementation and fecal microbiota transplantation in the management of UC.

RevDate: 2022-09-23

Khanna S, Sims M, Louie TJ, et al (2022)

SER-109: An Oral Investigational Microbiome Therapeutic for Patients with Recurrent Clostridioides difficile Infection (rCDI).

Antibiotics (Basel, Switzerland), 11(9): pii:antibiotics11091234.

Clostridioides&nbsp;difficile infection (CDI) is classified as an urgent health threat by the Centers for Disease Control and Prevention (CDC), and affects nearly 500,000 Americans annually. Approximately 20-25% of patients with a primary infection experience a recurrence, and the risk of recurrence increases with subsequent episodes to greater than 40%. The leading risk factor for CDI is broad-spectrum antibiotics, which leads to a loss of microbial diversity and impaired colonization resistance. Current FDA-approved CDI treatment strategies target toxin or toxin-producing bacteria, but do not address microbiome disruption, which is key to the pathogenesis of recurrent CDI. Fecal microbiota transplantation (FMT) reduces the risk of recurrent CDI through the restoration of microbial diversity. However, FDA safety alerts describing hospitalizations and deaths related to pathogen transmission have raised safety concerns with the use of unregulated and unstandardized donor-derived products. SER-109 is an investigational oral microbiome therapeutic composed of purified spore-forming Firmicutes. SER-109 was superior to a placebo in reducing CDI recurrence at Week 8 (12% vs. 40%, respectively; p < 0.001) in adults with a history of recurrent CDI with a favorable observed safety profile. Here, we discuss the role of the microbiome in CDI pathogenesis and the clinical development of SER-109, including its rigorous manufacturing process, which mitigates the risk of pathogen transmission. Additionally, we discuss compositional and functional changes in the gastrointestinal microbiome in patients with recurrent CDI following treatment with SER-109 that are critical to a sustained clinical response.

RevDate: 2022-09-23

Campagnoli LIM, Marchesi N, Vairetti M, et al (2022)

Age-Related NAFLD: The Use of Probiotics as a Supportive Therapeutic Intervention.

Cells, 11(18): pii:cells11182827.

Human aging, a natural process characterized by structural and physiological changes, leads to alterations of homeostatic mechanisms, decline of biological functions, and subsequently, the organism becomes vulnerable to external stress or damage. In fact, the elderly population is prone to develop diseases due to deterioration of physiological and biological systems. With aging, the production of reactive oxygen species (ROS) increases, and this causes lipid, protein, and DNA damage, leading to cellular dysfunction and altered cellular processes. Indeed, oxidative stress plays a key role in the pathogenesis of several chronic disorders, including hepatic diseases, such as non-alcoholic fatty liver disease (NAFLD). NAFLD, the most common liver disorder in the Western world, is characterized by intrahepatic lipid accumulation; is highly prevalent in the aging population; and is closely associated with obesity, insulin resistance, hypertension, and dyslipidemia. Among the risk factors involved in the pathogenesis of NAFLD, the dysbiotic gut microbiota plays an essential role, leading to low-grade chronic inflammation, oxidative stress, and production of various toxic metabolites. The intestinal microbiota is a dynamic ecosystem of microbes involved in the maintenance of physiological homeostasis; the alteration of its composition and function, during aging, is implicated in different liver diseases. Therefore, gut microbiota restoration might be a complementary approach for treating NAFLD. The administration of probiotics, which can relieve oxidative stress and elicit several anti-aging properties, could be a strategy to modify the composition and restore a healthy gut microbiota. Indeed, probiotics could represent a valid supplement to prevent and/or help treating some diseases, such as NAFLD, thus improving the already available pharmacological intervention. Moreover, in aging, intervention of prebiotics and fecal microbiota transplantation, as well as probiotics, will provide novel therapeutic approaches. However, the relevant research is limited, and several scientific research works need to be done in the near future to confirm their efficacy.

RevDate: 2022-09-23

Innocente G, Patuzzi I, Furlanello T, et al (2022)

Machine Learning and Canine Chronic Enteropathies: A New Approach to Investigate FMT Effects.

Veterinary sciences, 9(9): pii:vetsci9090502.

Fecal microbiota transplantation (FMT) represents a very promising approach to decreasing disease activity in canine chronic enteropathies (CE). However, the relationship between remission mechanisms and microbiome changes has not been elucidated yet. The main objective of this study was to report the clinical effects of oral freeze-dried FMT in CE dogs, comparing the fecal microbiomes of three groups: pre-FMT CE-affected dogs, post-FMT dogs, and healthy dogs. Diversity analysis, differential abundance analysis, and machine learning algorithms were applied to investigate the differences in microbiome composition between healthy and pre-FMT samples, while Canine Chronic Enteropathy Clinical Activity Index (CCECAI) changes and microbial diversity metrics were used to evaluate FMT effects. In the healthy/pre-FMT comparison, significant differences were noted in alpha and beta diversity and a list of differentially abundant taxa was identified, while machine learning algorithms predicted sample categories with 0.97 (random forest) and 0.87 (sPLS-DA) accuracy. Clinical signs of improvement were observed in 74% (20/27) of CE-affected dogs, together with a statistically significant decrease in CCECAI (median value from 5 to 2 median). Alpha and beta diversity variations between pre- and post-FMT were observed for each receiver, with a high heterogeneity in the response. This highlighted the necessity for further research on a larger dataset that could identify different healing patterns of microbiome changes.

RevDate: 2022-09-23

Liu A, Gao W, Zhu Y, et al (2022)

Gut Non-Bacterial Microbiota: Emerging Link to Irritable Bowel Syndrome.

Toxins, 14(9): pii:toxins14090596.

As a common functional gastrointestinal disorder, irritable bowel syndrome (IBS) significantly affects personal health and imposes a substantial economic burden on society, but the current understanding of its occurrence and treatment is still inadequate. Emerging evidence suggests that IBS is associated with gut microbial dysbiosis, but most studies focus on the bacteria and neglect other communities of the microbiota, including fungi, viruses, archaea, and other parasitic microorganisms. This review summarizes the latest findings that link the nonbacterial microbiota with IBS. IBS patients show less fungal and viral diversity but some alterations in mycobiome, virome, and archaeome, such as an increased abundance of Candida albicans. Moreover, fungi and methanogens can aid in diagnosis. Fungi are related to distinct IBS symptoms and induce immune responses, intestinal barrier disruption, and visceral hypersensitivity via specific receptors, cells, and metabolites. Novel therapeutic methods for IBS include fungicides, inhibitors targeting fungal pathogenic pathways, probiotic fungi, prebiotics, and fecal microbiota transplantation. Additionally, viruses, methanogens, and parasitic microorganisms are also involved in the pathophysiology and treatment. Therefore, the gut nonbacterial microbiota is involved in the pathogenesis of IBS, which provides a novel perspective on the noninvasive diagnosis and precise treatment of this disease.

RevDate: 2022-09-20

Vaughn BP, Fischer M, Kelly CR, et al (2022)

Effectiveness and safety of colonic and capsule fecal microbiota transplantation for recurrent Clostridioides difficile infection.

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association pii:S1542-3565(22)00880-1 [Epub ahead of print].

BACKGROUND AND AIMS: Fecal microbiota transplantation (FMT) emerged as rescue treatment for multiply recurrent Clostridioides difficile infection (rCDI) non-responsive to standard therapy. However, estimation of FMT efficacy varies among different protocols and formulations, while placebo-controlled clinical trials have excluded most rCDI patients due to medical co-morbidities. This study aimed to determine the safety and effectiveness of capsule FMT (cap-FMT) and colonoscopy FMT (colo-FMT) for rCDI using standardized products in a large, multicentered, prospective real-world cohort.

METHODS: Clinical outcomes and adverse events after FMT performed for rCDI at six sites were captured in a prospective registry. FMT was performed using one of two standardized formulations of microbiota manufactured by the University of Minnesota Microbiota Therapeutics Program, freeze-dried/encapsulated or frozen-thawed/liquid. FMT administration route was determined by the treating physician. rCDI cure rate was assessed at 1 and 2 months. Safety data was collected within the first 72 hours and at 1 and 2 months. Logistic regression was used to investigate factors associated with FMT failure.

RESULTS: Three hundred and one FMTs were performed in 269 unique patients. Two-thirds were cap-FMT. CDI cure rates were 86% (95% CI: 82%, 90%) at 1-month and 81% (95% CI: 75%, 86%) at 2-months. There was no difference in the 1-month or 2-month cure rate between cap- and colo-FMT. Cap-FMT recipients were older and less likely to be immunosuppressed or have inflammatory bowel disease. Patient factors of older age and hemodialysis were associated with FMT failure by 2-months on multivariate logistic regression. Additionally, post FMT antibiotic use was associated with FMT failure at 2-months. One SAE was related to colonoscopy (aspiration pneumonia), otherwise no new safety signals were identified.

CONCLUSIONS: Cap-FMT using freeze dried capsules has a similar safety and effectiveness profile compared to colo-FMT, without the procedural risks of colonoscopy. While highly effective overall, patient selection is a key factor to optimizing FMT success.

RevDate: 2022-09-20

Zhang Q, Li T, Niu J, et al (2022)

Inhibitory effects of antibiotic-induced gut microbiota depletion on acute itch behavior in mice.

Brain research bulletin pii:S0361-9230(22)00254-4 [Epub ahead of print].

BACKGROUND: The gut microbiota is known to be associated with the regulation of many neurological diseases and behaviors, including chronic pain. However, it is unclear whether the gut microbiota is critical to the itch sensation. In this study, we investigated the effects of gut microbiota depletion on acute itch.

METHODS: First, an antibiotic cocktail was orally administered to deplete the gut microbiota in male C57BL/6 mice. Then, pruritogens were intradermally injected to induce acute itch behavior. In addition, antibiotic-treated mice received transplantation of fecal microbiota from untreated mice, followed by tests for acute itch. The changes in c-Fos expression in trigeminal ganglia (TG) neurons were also investigated by immunofluorescence staining.

RESULTS: Our results indicated that chronic antibiotic treatment significantly reduced the diversity and richness of the gut microbiota of mice. Compared to vehicle-treated mice, antibiotic-treated mice showed reductions in acute itch behavior induced by compound 48/80, chloroquine (CQ), and serotonin (5-HT), respectively. Moreover, repositioning of microbiota reversed the reductions in acute itch behavior in antibiotic-treated mice. In addition, immunofluorescence staining revealed that antibiotic-treated mice displayed decreased c-Fos expression in ipsilateral TG compared to controls.

CONCLUSIONS: Our study, for the first time, discovered that antibiotic-induced gut microbiota depletion could reduce acute itch behavior, which may be connected with decreased TG neuronal activity.

RevDate: 2022-09-20

Xia Y, Tian Y, Zhou D, et al (2022)

Gut microbiota involved in spermatogenic function of Sancai Lianmei granules in obese mice.

Naunyn-Schmiedeberg's archives of pharmacology [Epub ahead of print].

Obesity is a well-established cause of reduced fertility and semen quality in men. Current evidence suggests that Sancai Lianmei granules (SCLM) effectively improve sexual function and semen quality in diabetic patients, while the gut microbiota can influence disease metabolism through various mechanisms. However, the effect of SCLM on the obesity-induced decrease in semen quality and on the gut microbiota is unclear. This study aimed to investigate the effects of SCLM on spermatogenic function and gut microbiota in obese mice. Obese mice were induced by a high-fat diet, and lipid metabolism, spermatogenic function, inflammatory factors, oxidative stress, and autophagy were analyzed to determine the effects of SCLM and SCLM-fecal microbiota transplantation (FMT). In addition, changes in the gut microbiota of mice were analyzed. SCLM and SCLM + FMT could effectively reduce the levels of total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL); decrease the expression of oxidative stress products malondialdehyde (MDA) and 8-hydroxyde-oxyguanosine (8-OHdG); and increase sperm density and sperm viability in obese mice while inhibiting the inflammatory responses and excessive cellular autophagy, indicating that SCLM and SCLM + FMT exerted a protective effect on spermatogenic functions. Furthermore, SCLM affected the gut microbiota composition in mice. This study determined that obesity can lead to reduced sperm motility and affect the composition of the gut microbiota, while SCLM can regulate blood lipids in mice directly or indirectly by regulating gut microbiota changes, and may improve sperm motility in obese mice by reducing oxidative stress and autophagy. In addition, FMT enhanced this effect, which may be related to the diversity of gut microbiota.

RevDate: 2022-09-19

Singh A, Mahajan R, Kahlon BK, et al (2022)

Early fecal microbiome transfer after donor defecation determines response in patients with moderate to severe ulcerative colitis.

Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology [Epub ahead of print].

BACKGROUND: Fecal microbiome transfer (FMT) targeting gut microbiome dysbiosis is an emerging therapy for ulcerative colitis (UC). There is however no consensus on protocols for performing FMT in UC, especially in relation to time after donor feces defecation.

METHODS: This is a single-center retrospective analysis of patients with moderate-severe UC (total Mayo Clinic score ≥6 and endoscopic Mayo Clinic subscore of ≥2) treated with FMT between September 2017 and December 2019 at Dayanand Medical College and Hospital, Ludhiana, India. Fresh fecal samples from unrelated healthy voluntary donors were administered through colonoscopy at weeks 0, 2, 6, 10, 14, 18, and 22. Time interval between donor feces defecation and FMT procedure was recorded for each FMT session and the mean time of seven sessions was designated aika. Impact of aika on clinical response and safety of FMT was evaluated.

RESULTS: During the study period, 123 adult patients (mean age 33.75±11.97 years, 61.8% [n=76] males) with moderate-severe UC (mean total Mayo Clinic and endoscopic Mayo Clinic scores 7.49±1.60 and 2.50±0.50, respectively) were treated with FMT. The mean aika was 2.29±0.75 h. The aika was smaller in patients who responded to FMT as compared to non-responders (2.13±0.75 h vs. 2.71±0.76 h, p=0.0002) as well as in patients achieving clinical remission (2.15±0.76 h vs. 2.42±0.76 h, p=0.05). There was no significant impact of aika on adverse effects except for the incidence of borborygmi after FMT, which was higher in patients with aika ≤2 h.

CONCLUSION: Early FMT after donor feces defecation favorably impacts the clinical response rates in patients with active UC.

RevDate: 2022-09-20
CmpDate: 2022-09-20

Ye C, Chen QY, Yan YM, et al (2022)

[Establishment and preliminary clinical application of human intestinal fluid transplantation].

Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery, 25(9):819-825.

Objective: To explore and establish the preparation system of human intestinal fluid transplantation (HIFT) and HIFT capsule, and to preliminarily apply it to clinic. Methods: Strict standards for donor screening and management were established. The nasojejunal tube was catheterized into the distal jejunum, and then it was connected with an improved disposable sterile negative pressure collection device for the collection of human intestinal fluid. After that, it was prepared into capsules by filtering, adding 10% glycerin protectant and freeze-drying method. The amount of living bacteria was used as the standard of therapeutic dose. The living bacteria amount in fluid is ≥ 5.0×108 /mL and the living bacteria proportion is ≥ 83%; the living bacteria amount in powder is ≥ 2.0×106 /g and the living bacteria proportion is ≥ 81%; The observational indicators included: (1) the basic information of the donor, the amount of living bacteria in the HIF and powder. (2) Preliminary analysis of the treatment for ASD, which combined HIFT capsule with standard FMT capsule, from February to December 2021 (Clinical trial Registration Number: ChiCTR2100043929). Evaluation criteria: Trypan blue staining method was used to detect the living bacteria amount in fluid and powder. The Autism Behavior Checklist (ABC) and Childhood Autism Rating Scale (CARS) were used to evaluate the efficacy. Results: Compared with the parent donor, the standard donor was younger [(25.4±0.9) y vs. (30.7±3.2) y, t=-19.097, P=0.001] and had a lower body mass index [(19.7±0.5) kg/m2 vs. (20.8±1.3) kg/m2, t=-8.726, P=0.001], more in the living bacteria amount in powder [(7.47±1.52)×106/g vs. (5.03±1.38)×106/g, t=11.331, P=0.031], Chao index (205.4±6.8 vs. 194.2±7.2, t=10.415, P=0.001), and Shannon index (3.25±0.14 vs 2.72±0.27, t=19.465, P=0.001). The differences were statistically significant (all P<0.05). However, there were no significant differences in gender, drainage volume and total number of bacterial liquid colonies between the two groups (all P>0.05). Both the standard donor and the parent donor met the donor screening criteria, and the preparation fluid and powder met the treatment criteria. Eight patients received the treatment of HIFT combined with fecal microbiota transplantation (FMT). Preliminary statistical results showed that HIFT combined with FMT improved ABC and CARS at the 1st, 2nd, 3rd and 4th months. The differences were statistically significant (all P<0.05). No severe adverse reaction occurred. Conclusion: Based on the previous research on FMT preparation system and the clinical technology in our center, this study developed a high standard HIFT preparation system, and explored the clinical study of HIFT combined with FMT, in order to provide an innovative therapy for the treatment of diseases.

RevDate: 2022-09-20
CmpDate: 2022-09-20

Ye C, Chen QY, Ma XQ, et al (2022)

[Long-term outcomes of 328 patients with of autism spectrum disorder after fecal microbiota transplantation].

Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery, 25(9):798-803.

Objective: To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) in the treatment of autism spectrum disorder (ASD). Methods: A longitudinal study was conducted. Clinical data from ASD patients with gastrointestinal symptoms and who underwent FMT in the Tenth People's Hospital affiliated to Tongji University or Jinling Hospital between May 2012 to May 2021 were retrospectively collected. Scores derived from the autism behavior checklist (ABC), the childhood autism rating scale (CARS), the Bristol stool form scale (BSFS), and the gastrointestinal symptom rating scale (GSRS) were analyzed at baseline and at the 1st, 3rd, 6th, 12th, 24th, 36th, 48th and 60th month after FMT. Records of any adverse reactions were collected. Generalized estimating equations were used for analysis of data on time points before and after FMT. Results: A total of 328 patients met the inclusion criteria for this study. Their mean age was 6.1±3.4 years old. The cohort included 271 boys and 57 girls. The percentage of patients remaining in the study for post-treatment follow-up at the 1st, 3rd, 12th, 24th, 36th, 48th and 60th month were as follows: 303 (92.4%), 284 (86.7%), 213 (64.9%), 190 (57.9%), 143 (43.6%), 79 (24.1%), 46 (14.0%), 31 (9.5%). After FMT, the average ABC score was significantly improved in the first 36 months and remained improved at the 48th month. However, the average score was not significantly different from baseline by the 60th month (1st-36th month, P<0.001; 48th month, P=0.008; 60th month, P=0.108). The average CARS score improved significantly during the first 48 months and remained improved at the 60th month (1st-48th month, P<0.001; 60th month, P=0.010). The average BSFS score was also significantly improved in the first 36 months (with an accompanying stool morphology that resembled type 4). This improvement was maintained at the 48th month. However, the average score was similar to baseline at the 60th month (1st-36th month, P<0.001; 48th month, P=0.008; 60th month, P=0.109). The average GSRS score was significantly improved during the first 24 months, but not afterwards (1st-24th month, P<0.001; 36th month, P=0.209; 48th month, P=0.996; 60th month, P=0.668). The adverse events recorded during treatment included abdominal distension in 21 cases (6.4%), nausea in 14 cases (4.3%), vomiting in 9 cases (2.7%), abdominal pain in 15 cases (4.6%), diarrhea in 18 cases (5.5%), fever in 13 cases (4.0%), and excitement in 24 cases (7.3%). All adverse reactions were mild to moderate and improved immediately after suspension of FMT or on treatment of symptoms. No serious adverse reactions occurred. Conclusion: FMT has satisfactory long-term efficacy and safety for the treatment of ASD with gastrointestinal symptoms.

RevDate: 2022-09-20
CmpDate: 2022-09-20

Lin ZL, Lu JB, Chen QY, et al (2022)

[Clinical effectiveness of fecal microbiota transplantation combined with nutritional support and psychological intervention in patients with "Tetralogy of Tongji"].

Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery, 25(9):784-791.

Objective: To summarize and analyze the clinical effect of fecal microbiota transplantation (FMT) combined with nutritional support and psychotherapy in patients with "Tetralogy of Tongji" (comprising chronic gastrointestinal dysfunction, mental and psychological disorders, malnutrition, and endocrine disorders). Methods: A longitudinal study was conducted. The inclusion criteria were as follows: (1) patients were under 70 years of age; (2) patients exhibited chronic gastrointestinal dysfunction (in accordance with the Rome IV diagnostic criteria for irritable bowel syndrome ie. chronic functional constipation, diarrhea, abdominal pain and abdominal distention) with onset occurring more than one year previously; (3) patients exhibited malnutrition (body mass index ≤ 18.5 kg/m2); (4) patients exhibited depression, anxiety, or state as diagnosed by a psychologist using the Hamilton anxiety rating scale (HAMA) and the Hamilton depression scale (HAMD); (5) patients were women of childbearing age with amenorrhea or menstrual disorder with a duration ≥6 months. Patients were excluded if they exhibited gastrointestinal bleeding, short bowel syndrome, radiation-induced intestinal injury, intestinal obstruction or inflammatory bowel disease, recurrent/metastatic tumors, systemic infectious diseases, life-threatening systemic comorbidities, intorlerate to nasojejunal, percutaneous gastrostomy / jejunostomy or FMT. The clinical data of 43 patients at Shanghai Tenth People's Hospital exhibiting the "Tetralogy of Tongji" and who received microflora transplantation combined with nutritional support and psychotherapy from June 2017 to June 2021 was prospectively collected. There were 12 males and 31 females with a mean age of 35.2±16.7 years. All 43 patients had chronic gastrointestinal dysfunction. Of these, 24 patients had depression and 19 had anxiety. There were 26 women of reproductive age, including 13 cases of menstrual disorder and 9 cases of amenorrhea. The treatment intervention was a combination of FMT (microflora solution or microflora capsule), nutritional support (enteral nutrition) and psychological intervention. The following were assessed before treatment and 1, 3, 6 months after treatment: (1) gastrointestinal function was assessed using the gastrointestinal symptoms rating scale (GSRS), where a higher score is indicative of more serious gastrointestinal symptoms, and the gastrointestinal quality of life index (GIQLI), where a higher score is indicative of higher quality of life; (2) psychological status was assessed using HAMA and HAMD scores, where a lower score is indicative of reduced severity of anxiety or depression symptoms, respectively; (3) nutritional status was assessed by measurements of total blood protein, albumin, fibrinogen and prealbumin, as well as measurements of body mass and body mass index (BMI); (4) neuroendocrine function was assessed by measurement of blood levels of cortisol, dopamine and noradrenaline, as well as menstruation in women of reproductive age. Results: The follow-up rates at 1, 3 and 6 months after treatment were 90.7% (39/43), 72.1% (31/43) and 55.8% (24/43), respectively. The total effective rate for chronic gastrointestinal dysfunction was 81.4% (35/43), of which the average GSRS score decreased from 29.35±3.56 before treatment to 18.25±2.56 in the sixth month (P<0.001). The average GIQLI score increased from 56.23±10.34 before treatment to 91.04±20.39 in the sixth month (P<0.001). All patients had malnutrition before treatment. After 6 months, their body weight had increased from 40.61±8.88 kg to 50.45±6.23 kg (P<0.001), and BMI had increased from 15.17±1.87 kg/m2 to 19.58±1.42 kg/m2 (P<0.001). The average total protein level was 60.99± 5.99 g/L before treatment. After 6 months, this had increased to 64.21±4.23 g/L (F=2.715, P=0.022). The average prealbumin level increased from 150.14±56.04 mg/L before treatment to 258.17±86.94 mg/L after 6 months (F=15.124, P<0.001). In this study, 24 patients with depression/depressed state were included. After treatment, the average HAMD score in these patients decreased from 22.79±6.63 before treatment to 9.92±7.24 after 6 months (P<0.001). There were 19 patients with anxiety disorder/anxiety state. After treatment, the average HAMA score in these patients decreased from 17.15±4.34 before treatment to 7.73±4.10 after 6 months (P<0.001). Observing the endocrine efficacy of 26 women of childbearing age, it was found that the effective rate of this treatment on endocrine regulation was 69.2% (18/26). Although there was no significant change in blood cortisol levels after 6 months, average blood dopamine levels decreased from 32.91±10.65 nmol/L before treatment to 13.02±5.58 nmol/L after 6 months (P<0.001). Average blood norepinephrine levels decreased from 49.75±15.23 ng/L before treatment to 19.21±9.58 ng/L after 6 months (P<0.001). Conclusion: The strategy of FMT combined with nutritional support and psychological intervention is effective in improving the symptoms of the "Tetralogy of Tongji".

RevDate: 2022-09-20
CmpDate: 2022-09-20

Chen QY, Lu JB, Qin HL, et al (2022)

[Clinical significance and intervention strategy of gastrointestinal psychiatry].

Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery, 25(9):771-776.

With the development of global economy and society,the number of patients who suffer from functional gastrointestinal disorders (FGID) and mental illness is growing. In recent years, a substantial amount of high-quality research evidence shows that these two kinds of diseases often coexist, and they are mutually causal, and their common pathophysiology is the abnormal interaction of "bacteria-gut-brain axis". In clinical practice, there are some problems, such as insufficient recognition and attention of both doctors and patients to its clinical manifestations, lack of understanding of pathophysiological mechanism, and lack of overall and integrated views of intervention methods, which may be the main factors of poor curative effect at present. Therefore, according to the global research progress and the author's clinical experience, we put forward a new viewpoint of "gastrointestinal psychiatry", it concluded that clinical intervention strategies needed to include dietary and lifestyle changes as well as multidisciplinary interventions such as probiotics, prebiotic, fecal microbiota transplantation and cognitive psychology. On the basis of gastrointestinal psychiatry, this paper systematically elaborated the diagnosis and treatment of this kind of diseases.

RevDate: 2022-09-20
CmpDate: 2022-09-20

Qin HL, Chen QY, N Li (2022)

[Further improve the standardization construction and development level of fecal microbiota transplantation (FMT) in China].

Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery, 25(9):766-770.

In the past ten years, the clinical application of fecal microbiota transplantation (FMT) in the treatment of intestinal and extraintestinal diseases has attracted much attention. In China, there are more than 300 hospitals that have developed FMT, but the development of FMT is still in its early stage. The clinical practice of FMT needs to form a standardized system, including management of donors and acceptors, preparation of capsules containing certain gut bacteria, evaluation of effectiveness, and study of fecal microbiota and disease. In order to promote the establishment of the standard system of FMT and the healthy development of FMT, this paper expounds the establishment of the standardization of domestic flora transplantation according to the relevant literature, as well as the experience of 10000 cases and 95300 times of FMT in our center.

RevDate: 2022-09-20
CmpDate: 2022-09-20

Society of Parenteral and Enteral Nutrition, Chinese Medical Association, Microecology Professional Committee of Shanghai Preventive Medicine Association (2022)

[Chinese expert consensus on screening and management of fecal microbiota transplantation donors (2022 edition)].

Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery, 25(9):757-765.

Fecal microbiota transplantation (FMT) has been recommended by clinical practical guidelines and consensus for the treatment of a variety of intestinal diseases, but in more and more medical institutions trying to develop this technology in clinical practice, how to screen and manage donors has become an urgent need for regulation. In view of this, based on evidence-based medical evidence, Society of Parenteral and Enteral Nutrition of Chinese Medical Association and Microecology Professional Committee of Shanghai Preventive Medicine Association jointly formulate an expert consensus on the screening and management of donors, including screening on the internet and in clinic, evaluation and selection during donation, establishment of the standard of donor management, the follow-up system and the professional support system, with a view to improving the quality of microbiota transplantation donors, reducing adverse events, and promoting the standardized clinical application of FMT.

RevDate: 2022-09-20
CmpDate: 2022-09-20

National Institute of Hospital Administration, NHC, Society of Parenteral and Enteral Nutrition, Chinese Medical Association, Intestinal Microecology Cooperative Group, Chinese Society for Parenteral and Enteral Nutrition (2022)

[Expert consensus on clinical application management of fecal microbiota transplantation (2022 edition)].

Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery, 25(9):747-756.

Fecal microbiota transplantation (FMT) is to transplant the functional intestinal bacteria from human feces into the intestinal tract of patients, reconstruct the new intestinal flora and treat intestinal and extra-intestinal diseases. During the past 10 years, FMT has made a breakthrough in the treatment of intestinal and extra-intestinal diseases, and provided a brand-new strategy to the treatment of intestinal and extra-intestinal diseases. In view of the fact that FMT lacks a unified clinical management standard at home and abroad, relevant regulations and policies still need to be improved, and clinical application experience still needs to be accumulated, the National Institute of Hospital Administration, National Health Commission commissioned a clinical FMT expert working group to organize experts in related fields. Based on thorough analysis of relevant literature, policies and norms internationally, as well as the mature experience of FMT in many medical institutions in China, an expert consensus for clinical management of FMT in medical institutions is compiled to further strengthen its clinical application and standard management, so as to improve the safety and efficacy of FMT.

RevDate: 2022-09-18

Ianiro G, Mullish BH, Iqbal TH, et al (2022)

Minimising the risk of monkeypox virus transmission during faecal microbiota transplantation: recommendations from a European expert panel.

The lancet. Gastroenterology & hepatology pii:S2468-1253(22)00305-3 [Epub ahead of print].

RevDate: 2022-09-20

Pu Y, Zhang Q, Tang Z, et al (2022)

Correction: Fecal microbiota transplantation from patients with rheumatoid arthritis causes depression-like behaviors in mice through abnormal T cells activation.

Translational psychiatry, 12(1):387 pii:10.1038/s41398-022-02168-6.

RevDate: 2022-09-17

Abdelghafar YA, AbdelQadir YH, Motawea KR, et al (2022)

Efficacy and safety of fecal microbiota transplant in irritable bowel syndrome: An update based on meta-analysis of randomized control trials.

Health science reports, 5(5):e814.

Background and Aims: Fecal microbiota transfer (FMT) is a potential treatment for irritable bowel syndrome (IBS). Several randomized trials have tested FMT effects using different routes of administration, doses, and sample sizes. We aim to assess the overall efficacy of FMT for IBS patients and the safety of the intervention.

Methods: We systematically searched four databases for randomized control trials that studied the efficacy and safety of FMT in IBS patients.

Results: We included 8 randomized trials (472 patients) that compared FMT with placebo in IBS patients. Pooled results showed no statistically significant difference between FMT and control groups in the overall change in IBS symptom severity (IBS-SSS) at 1 month (p = 0.94), 3/4 months (p = 0.82), and at the end of trials (p = 0.67). No significant difference in the total number of respondents between the FMT and control groups (risk ratios = 1.84, [95% confidence interval (CI) = 0.82-2.65], p = 0.19). Although the oral route of administration showed a significant difference in the number of respondents (p = 0.004), there was no statistically significant difference in the IBS-SSS when subgrouping the oral route of administration (mean difference = 47.57, [95% CI = -8.74-103.87], p = 0.10).

Conclusion: FMT is not an effective treatment to relieve all the symptoms of IBS. Even in the groups that showed relatively significant improvement after FMT, the effect was proven to wear off over time and the re-administration carries a low success rate. Future research should consider different bacterial-based interventions such as probiotics or specific antibiotics.

RevDate: 2022-09-15

Ianiro G, Punčochář M, Karcher N, et al (2022)

Variability of strain engraftment and predictability of microbiome composition after fecal microbiota transplantation across different diseases.

Nature medicine [Epub ahead of print].

Fecal microbiota transplantation (FMT) is highly effective against recurrent Clostridioides difficile infection and is considered a promising treatment for other microbiome-related disorders, but a comprehensive understanding of microbial engraftment dynamics is lacking, which prevents informed applications of this therapeutic approach. Here, we performed an integrated shotgun metagenomic systematic meta-analysis of new and publicly available stool microbiomes collected from 226 triads of donors, pre-FMT recipients and post-FMT recipients across eight different disease types. By leveraging improved metagenomic strain-profiling to infer strain sharing, we found that recipients with higher donor strain engraftment were more likely to experience clinical success after FMT (P = 0.017) when evaluated across studies. Considering all cohorts, increased engraftment was noted in individuals receiving FMT from multiple routes (for example, both via capsules and colonoscopy during the same treatment) as well as in antibiotic-treated recipients with infectious diseases compared with antibiotic-naïve patients with noncommunicable diseases. Bacteroidetes and Actinobacteria species (including Bifidobacteria) displayed higher engraftment than Firmicutes except for six under-characterized Firmicutes species. Cross-dataset machine learning predicted the presence or absence of species in the post-FMT recipient at 0.77 average AUROC in leave-one-dataset-out evaluation, and highlighted the relevance of microbial abundance, prevalence and taxonomy to infer post-FMT species presence. By exploring the dynamics of microbiome engraftment after FMT and their association with clinical variables, our study uncovered species-specific engraftment patterns and presented machine learning models able to predict donors that might optimize post-FMT specific microbiome characteristics for disease-targeted FMT protocols.

RevDate: 2022-09-15

Schmidt TSB, Li SS, Maistrenko OM, et al (2022)

Drivers and determinants of strain dynamics following fecal microbiota transplantation.

Nature medicine [Epub ahead of print].

Fecal microbiota transplantation (FMT) is a therapeutic intervention for inflammatory diseases of the gastrointestinal tract, but its clinical mode of action and subsequent microbiome dynamics remain poorly understood. Here we analyzed metagenomes from 316 FMTs, sampled pre and post intervention, for the treatment of ten different disease indications. We quantified strain-level dynamics of 1,089 microbial species, complemented by 47,548 newly constructed metagenome-assembled genomes. Donor strain colonization and recipient strain resilience were mostly independent of clinical outcomes, but accurately predictable using LASSO-regularized regression models that accounted for host, microbiome and procedural variables. Recipient factors and donor-recipient complementarity, encompassing entire microbial communities to individual strains, were the main determinants of strain population dynamics, providing insights into the underlying processes that shape the post-FMT gut microbiome. Applying an ecology-based framework to our findings indicated parameters that may inform the development of more effective, targeted microbiome therapies in the future, and suggested how patient stratification can be used to enhance donor microbiota colonization or the displacement of recipient microbes in clinical practice.

RevDate: 2022-09-19
CmpDate: 2022-09-19

Koo H, CD Morrow (2022)

Time series strain tracking analysis post fecal transplantation identifies individual specific patterns of fecal dominant donor, recipient, and unrelated microbial strains.

PloS one, 17(9):e0274633.

BACKGROUND: Fecal microbial transplantation (FMT) has been used with the therapeutic intent to change the functions of the gut microbial community in metabolism and host immunity. For most of these therapies, the recipients are not given antibiotics to eliminate the microbial community prior to transplant with donor fecal microbes resulting in the initial gut microbial community following FMT consisting of a consortium of donor and recipient microbes. The detailed analysis of the fecal samples from these FMT over time provides a unique opportunity to study the changes in the gut microbial strain community that occurs following the introduction of new microbial strains (donor) into an established community (recipient).

METHODS: In this study, we have metagenomic data set consisting of 5 FMT that contained donor, recipient and recipient post FMT taken multiple times for periods up to 535 days after the FMT. We used two established strain tracking methods, Window-based Single Nucleotide Variant (SNV) Similarity (WSS) and StrainPhlAn, to determine the presence of donor and recipient microbial strains following FMT. To assess recombination between donor and recipient strains of Bacteroides vulgatus post FMT, we used BLAST+ to analyze the data sets for Bacteroidales-specific antimicrobial proteins (BSAP-3) that have known functions to restrict species specific replication.

RESULTS: We found that Alistipes onderdonkii, Alistipes shahii, Alistipes putredinis, and Parabacteroides merdae, all had patterns post FMT consisting of either dominant donor or recipient microbial strains in the feces. In contrast, the analysis of Bacteroides spp. in five FMT pairs revealed inter-individual oscillation over time with the appearance of either donor or recipient fecal strain dominance. In some instances, B. vulgatus and B. uniformis were also identified after FMT that were not related to either the donor or recipient. Finally, in one of the FMT, we identified a distinct B. vulgatus strain post-FMT that matched the pre-FMT strain but was BSAP-3 positive, suggesting a possible recombination event between the donor and recipient strains.

CONCLUSION: The complex oscillating patterns of the appearance of fecal dominant donor, recipient or unrelated strains following extended times post FMT provide new insights into the dynamics of the microbial community interactions with the recipients following FMT. The result from our analysis has implications for the use of FMT to predictably change the biological functions of the gut community in metabolism and host immunity.

RevDate: 2022-09-17

Shi D, Turroni S, Gong L, et al (2022)

Editorial: Manipulation of gut microbiota as a key target to intervene on the onset and progression of digestive system diseases.

Frontiers in medicine, 9:999005.

RevDate: 2022-09-17

Deluce J, Maleki Vareki S, R Fernandes (2022)

The role of gut microbiome in immune modulation in metastatic renal cell carcinoma.

Therapeutic advances in medical oncology, 14:17588359221122714.

Treatment of metastatic renal cell carcinomas (mRCC) has drastically improved since the advent of immunotherapy with immune checkpoint inhibitors (ICIs), with a significant proportion of patients achieving durable responses. While this has revolutionized treatment and improved outcomes for mRCC patients, a large subset of patients still does not respond to treatment with ICIs. Moreover, ICIs can induce various immune-related adverse events, limiting their use in many patients. Therefore, there is a need to identify the predictive biomarkers of both efficacy and toxicity associated with ICIs, which would allow for a more personalized approach and help with clinical decision-making. This review aims to explore the role of the gut microbiome in RCC to overcome primary resistance and predict response to treatment with ICIs. First, current therapeutic strategies and mechanisms of action of ICI therapies for RCC treatment will be reviewed. With the technological development of shotgun whole-genome sequencing, the gut microbiome has emerged as an exciting field of research within oncology. Thus, the role of the microbiome and its bidirectional interaction with ICIs and other drugs will be explored, with a particular focus on the microbiome profile in RCC. Lastly, the rationale for future clinical interventions to overcome resistance to ICIs using fecal microbiota transplantation in patients with RCC will be presented.

RevDate: 2022-09-14

Wang Y, Zhang S, Borody TJ, et al (2022)

Encyclopedia of fecal microbiota transplantation: a review of effectiveness in the treatment of 85 diseases.

Chinese medical journal [Epub ahead of print].

ABSTRACT: Fecal microbiota transplantation (FMT) has been used as a core therapy for treating dysbiosis-related diseases by remodeling gut microbiota. The methodology and technology for improving FMT are stepping forward, mainly including washed microbiota transplantation (WMT), colonic transendoscopic enteral tubing (TET) for microbiota delivery, and purified Firmicutes spores from fecal matter. To improve the understanding of the clinical applications of FMT, we performed a systematic literature review on FMT published from 2011 to 2021. Here, we provided an overview of the reported clinical benefits of FMT, the methodology of processing FMT, the strategy of using FMT, and the regulations on FMT in global. A total of 782 studies were included for the final analysis. The present review profiled the effectiveness from all clinical FMT uses in 85 specific diseases as eight categories, including infections, gut diseases, microbiota-gut-liver axis, microbiota-gut-brain axis, metabolic diseases, oncology, hematological diseases, and other diseases. Although many further controlled trials will be needed, the dramatic increasing reports have shown the promising future of FMT for dysbiosis-related diseases in the gut or beyond the gut.

RevDate: 2022-09-19

Hu C, Li J, Liu M, et al (2022)

Young fecal transplantation modulates the visual toxicity of perfluorobutanesulfonate in aged zebrafish recipients.

Aquatic toxicology (Amsterdam, Netherlands), 251:106295 pii:S0166-445X(22)00221-1 [Epub ahead of print].

Perfluorobutanesulfonate (PFBS) is an emerging pollutant of potent toxicity to impair visual system. Previous studies highlighted the applicability of gut microbiota manipulation to mitigate the toxicities of PFBS. However, it remains unknown whether transplantation of whole fecal microbiota to PFBS-disturbed gut can restore the health of the recipient animals, especially for aged fish that are of high susceptibility. In the present study, aged zebrafish of 3 years old were first transplanted with feces from young counterparts and then exposed to environmentally relevant concentrations of PFBS. After exposure, toxic effects of PFBS on visual system of aged zebrafish were elucidated based on transcriptional, proteomic, biochemical, histological, and behavioral evidences. In addition, interaction between young fecal transplant and innate visual toxicity of PFBS was further explored in the aged. The results showed that PFBS singular exposure induced lipid peroxidation (by 1.9-fold) in aged male eyes, which were alleviated by young fecal transplantation. PFBS also disturbed the retinal structure of the aged, which was characterized by increases in plexiform layers, but decreases in ganglion neuron number (by 26.8% and 26.0% in males and females, respectively) and optic nerve width (by 14.1% and 12.7% in males and females, respectively). It was unexpected that young fecal transplant was very potent in re-organizing the histological assembly of aged eyes regardless of PFBS coexposure, underlining the intimate interplay between gut and retina. Proteomic profiling provided more clues about the visual toxicology mechanism of PFBS, which was found to typically interfere with synaptic neurotransmission occurring in plexiform layers. However, proteome perturbation of aged eyes by PFBS exposure was effectively shifted by the transplantation of young feces towards the control phenotype, suggesting the high ameliorative potential of young fecal transplantation along the gut-retina axis. Overall, the present study pinpoints the potent visual toxicity of PFBS in aged animals and highlights the efficacy of young fecal transplant to regulate the inherent toxicity of PFBS. Future studies are necessitated to sequence the gut microbiota and unveil the underlying interactive routes between gut microbes and visual system.

RevDate: 2022-09-17
CmpDate: 2022-09-15

Bai X, Sun Y, Li Y, et al (2022)

Landscape of the gut archaeome in association with geography, ethnicity, urbanization, and diet in the Chinese population.

Microbiome, 10(1):147.

BACKGROUND AND AIMS: The human gut is home to a largely underexplored microbiome component, the archaeome. Little is known of the impact of geography, urbanization, ethnicity, and diet on the gut archaeome in association with host health. We aim to delineate the variation of the human gut archaeome in healthy individuals and its association with environmental factors and host homeostasis.

METHODS: Using metagenomic sequencing, we characterized the fecal archaeomes of 792 healthy adult subjects from 5 regions in China, spanning 6 ethnicities (Han, Zang, Miao, Bai, Dai, and Hani), consisting of both urban and rural residents for each ethnicity. In addition, we sampled 119 host variables (including lifestyle, diet, and blood parameters) and interrogated the influences of those factors, individually and combined, on gut archaeome variations.

RESULTS: Population geography had the strongest impact on the gut archaeome composition, followed by urbanization, dietary habit, and ethnicity. Overall, the metadata had a cumulative effect size of 11.0% on gut archaeome variation. Urbanization decreased both the α-diversity (intrinsic microbial diversity) and the β-diversity (inter-individual dissimilarities) of the gut archaeome, and the archaea-to-bacteria ratios in feces, whereas rural residents were enriched for Methanobrevibacter smithii in feces. Consumption of buttered milk tea (a characteristic diet of the rural Zang population) was associated with increased abundance of M. smithii. M. smithii was at the central hub of archaeal-bacterial interactions in the gut microecology, where it was positively correlated with the abundances of a multitude of short chain fatty acid (SCFA)-producing bacteria (including Roseburia faecis, Collinsella aerofaciens, and Prevotella copri). Moreover, a decreased abundance of M. smithii was associated with increased human blood levels of cholinesterase in the urban population, coinciding with the increasing prevalence of noncommunicable diseases (such as dementia) during urbanization.

CONCLUSIONS: Our data highlight marked contributions of environmental and host factors (geography, urbanization, ethnicity, and habitual diets) to gut archaeome variations across healthy individuals, and underscore the impact of urbanization on the gut archaeome in association with host health in modern society. Video Abstract.

RevDate: 2022-09-15
CmpDate: 2022-09-15

Pipek B, Valentová H, Fojtík P, et al (2022)

Faecal microbiota transplantation in the treatment of recurrent intestinal Clostridioides difficile infection - a ten-year single-center experience.

Casopis lekaru ceskych, 161(3-4):126-130.

Clostridioides difficile (Clostridium difficile in older taxonomy) is a gram-positive anaerobic and bacteria enabled by endospores. Clostridioides difficile is currently the main cause of nosocomial infections in developed countries. Due to the high probability of developing bacterial resistance to treatment and the numerous recurrences in multiple chronic conditions in older adults of our society it causes a widespread medical problem. Faecal microbiota transplantation (FMT) is a highly effective method for treating recurrent intestinal Clostridioides difficile infections (CDI). With this method the potential mechanism of effect is the transmission of a complex intestinal ecosystem, including vital microorganisms, from the donor to the recipient. Presenting the results of monocentric prospective monitoring: Primary aim of the study was to evaluate long-term remission (the continued absence of clinical manifestations of CDI 3 months after FMT administration). The secondary aim of the study was to monitor the short-term remission in the 7 days after FMT administration. Demographic data, information about CDI and the details of therapy were obtained and completed by the treating physician of each patient or by targeted questioning of the patient or their family. We used clinical monitoring to determine the effect of the treatment. The examinations of stool donors and the preparation for a faecal microbiota transplantation were performed according to the currently valid guidelines of the Czech Society of Infectious Diseases for the treatment of the recurrent bacterial infection Clostridioides difficile with faecal microbiota transplantation. The follow-ups took place from February 2011 to July 2021 in the gastroenterology department at the AGEL Ostrava-Vítkovice Hospital and included 116 patients with their first and subsequent recurrence of CDI that were treated with faecal bacteriotherapy. The median age of our patients was 71 years old (the youngest was 19 years old, the oldest 103 years old). 69 women and 47 men took part in the study. 56 patients had their first recurrence of CDI, 41 had a second attack, and 20 patients had a third and subsequent recurrences. In 62 patients (53.4 %), the route of FMT administration was a local enema into the left colon. With 37 patients (31.9 %) we used a colonoscopy after standard anterograde bowel preparation. With 12 patients (10.3 %) gastroscopy administration (deep into the duodenum) was used. 4 patients (3.5 %) were given a nasoenteral tube and one patient (0.9 %) was administered FMT per percutaneous endoscopic gastrostomy (PEG). We applied a frozen universal donor FMT in 81 patients (69.8 %), and a freshly prepared FMT from a person living in the same household was used in 35 patients (30.1 %). The secondary endpoint (the absence of clinical manifestations of CDI within 7 days of FMT administration) was achieved with 102 patients (87.9 %) in our study. The fulfilment of the primary endpoint (the development of long-term remission) was observed with 93 patients (80.2 %). An early administration of FMT appears to be a significant predictor of treatment effect (p = 0.05; OR 5.11; 95% CI 1.65-15.8). Faecal microbiota transplantation is an effective and safe therapy for recurrent intestinal Clostridioides difficile infection, and it respects the up-to-date guidelines for treatment. Of the 116 patients included in our study with first and subsequent CDI, we achieved long-term remission in 80.2 % of them. An early administration of FMT appears to be a significant predictor of treatment effect.

RevDate: 2022-09-20
CmpDate: 2022-09-13

Zhang ZJ, Lehmann CJ, Cole CG, et al (2022)

Translating Microbiome Research From and To the Clinic.

Annual review of microbiology, 76:435-460.

Extensive research has elucidated the influence of the gut microbiota on human health and disease susceptibility and resistance. We review recent clinical and laboratory-based experimental studies associating the gut microbiota with certain human diseases. We also highlight ongoing translational advances that manipulate the gut microbiota to treat human diseases and discuss opportunities and challenges in translating microbiome research from and to the bedside.

RevDate: 2022-09-13

Spindler MP, Siu SS, Mogno I, et al (2022)

Human gut microbiota stimulate defined innate immune responses that vary from phylum to strain.

Cell host & microbe pii:S1931-3128(22)00408-5 [Epub ahead of print].

The potential of commensal bacteria to modulate host immunity remains largely uncharacterized, largely due to the vast number of strains that comprise the human gut microbiota. We have developed a screening platform to measure the innate immune responses of myeloid cells to 277 bacterial strains isolated from the gut microbiota of healthy individuals and those with inflammatory bowel diseases. The innate immune responses to gut-derived bacteria are as strong as those toward pathogenic bacteria, and they vary from phylum to strain. Myeloid cells differentially rely upon innate receptors TLR2 or TLR4 to sense taxa, with differential sensing of Bacteroidetes and Proteobacteria that predict in vivo functions. These innate immune responses can be modeled using combinations of up to 8 Toll-like receptor (TLR) agonists. Furthermore, the immunogenicity of strains is stable over time and following fecal microbiota transplantation into new human recipients. Collectively, this high-throughput approach provides an insight into how commensal microorganisms shape innate immune phenotypes.

RevDate: 2022-09-12

Vasiliu O (2022)

Is fecal microbiota transplantation a useful therapeutic intervention for psychiatric disorders? A narrative review of clinical and preclinical evidence.

Current medical research and opinion [Epub ahead of print].

The therapeutic management of psychiatric disorders is currently confronted with a critical need to find new therapeutic interventions due to the high rates of non-responsivity or low responsivity in the key pathologies, e.g., schizophrenia spectrum disorders, alcohol use disorders, or major depressive disorder. The modulation of intestinal microbiota has been explored in various organic and psychiatric dysfunctions, with different degrees of success. However, this type of intervention may represent a helpful add-on at a conceptual level since it does not associate negative pharmacokinetics interactions, significant adverse events, or risk for non-adherence in the long term. Oral administration of pre-, pro-, or synbiotics, and especially the treatment with fecal microbiota transplantation (FMT), are methods still in their early research phase for patients with psychiatric disorders, therefore an exploration of data regarding the potential benefits and adverse events of FMT was considered necessary. In order to accomplish this purpose, the available results of research dedicated to each category of psychiatric disorders, starting with depressive and anxiety disorders, continuing with schizophrenia, substance use disorders, and finishing with disorders diagnosed during childhood, were presented in this paper. Seven clinical trials, 16 preclinical studies, three meta-analyses/systematic reviews, and six case reports, all of these representing ten distinct categories of psychiatric disorders or manifestations, have been reviewed. Mood disorders, anxiety disorders, and alcohol dependence have been the most extensively investigated clinical entities from the FMT efficacy and tolerability perspective, and reviewed data are generally promising. Based on the current status of research, FMT may be considered a helpful intervention in specific psychiatric pathologies. Still, this review showed that most of the information is derived from entirely preclinical studies. Therefore, clinical trials with sound methodology and more participants are needed to clarify FMT's benefits and risks in psychiatric disorders.

RevDate: 2022-09-13
CmpDate: 2022-09-13

Korpela K, WM de Vos (2022)

Infant gut microbiota restoration: state of the art.

Gut microbes, 14(1):2118811.

The gut microbiota has a central role in the programming of the host's metabolism and immune function, with both immediate and long-term health consequences. Recent years have witnessed an accumulation of understanding of the process of the colonization and development of the gut microbiota in infants. The natural gut microbiota colonization during birth is frequently disrupted due to C-section birth or intrapartum or postpartum antibiotic exposure, and consequently aberrant gut microbiota development is common. On a positive note, research has shown that restoration of normal gut microbiota development is feasible. We discuss here the current understanding of the infant microbiota, provide an overview of the sources of disturbances, and critically evaluate the evidence on early life gut microbiota restoration for improved health outcomes by analyzing published data from infant gut microbiota restoration studies.

RevDate: 2022-09-13
CmpDate: 2022-09-13

Li Z, Zhang Y, Hong W, et al (2022)

Gut microbiota modulate radiotherapy-associated antitumor immune responses against hepatocellular carcinoma Via STING signaling.

Gut microbes, 14(1):2119055.

Studies of the gut-liver axis have enhanced our understanding of the pathophysiology of various liver diseases and the mechanisms underlying the regulation of the effectiveness of therapies. Radiotherapy (RT) is an important therapeutic option for patients with unresectable hepatocellular carcinoma (HCC). However, the role of the microbiome in regulating the response to RT remains unclear. The present study characterizes the gut microbiome of patients responsive or non-responsive to RT and investigates the molecular mechanisms underlying the differences in patient response. We collected fecal samples for 16S rRNA sequencing from a prospective longitudinal trial of 24 HCC patients receiving RT. We used fecal microbiota transplantation (FMT), flow cytometry, and transcriptome sequencing to explore the effects of dysbiosis on RT. We also examined the role of stimulator of interferon genes (STING) in RT-associated antitumor immune responses mediated by gut microbiota in STING- (Tmem173-/-) and cGAS-knockout (Mb21d1-/-) mouse models. We propose that primary resistance to RT could be attributed to the disruption of the gut microbiome. Mechanistically, gut microbiome dysbiosis impairs antitumor immune responses by suppressing antigen presentation and inhibiting effector T cell functions through the cGAS-STING-IFN-I pathway. Cyclic-di-AMP - an emerging second messenger of bacteria - may act as a STING agonist and is thus a potential target for the prediction and modulation of responses to RT in HCC patients. Our study highlights the therapeutic potential of modulating the gut microbiome in HCC patients receiving RT and provides a new strategy for the radiosensitization of liver cancer.

RevDate: 2022-09-13

Zhang F, Zuo T, Wan Y, et al (2022)

Multi-omic analyses identify mucosa bacteria and fecal metabolites associated with weight loss after fecal microbiota transplantation.

Innovation (Cambridge (Mass.)), 3(5):100304.

Fecal microbiota transplantation (FMT) has shown promising results in animal models of obesity, while results in human studies are inconsistent. We aimed to determine factors associated with weight loss after FMT in nine obese subjects using serial multi-omics analysis of the fecal and mucosal microbiome. The mucosal microbiome, fecal microbiome, and fecal metabolome showed individual clustering in each subject after FMT. The colonic microbiome in patients showed more marked variance after FMT compared with the duodenal microbiome, characterized by an increased relative abundance of Bacteroides. Subjects who lost weight after FMT sustained enrichment of Bifidobacterium bifidum and Alistipes onderdonkii in the duodenal, colonic mucosal, and fecal microbiome and increased levels of phosphopantothenate biosynthesis and fecal metabolite eicosapentaenoic acid (EPA), compared with those without weight loss. Fecal levels of amino acid metabolism-associated were positively correlated with the fecal abundance of B. bifidum, and fatty acid metabolism-associated metabolites showed positive correlations with A. onderdonkii. We report for the first time the individualized response of fecal and mucosa microbiome to FMT in obese subjects and highlight that FMT is less capable of shaping the small intestine microbiota. These findings contribute to personalized microbe-based therapies for obesity.

RevDate: 2022-09-13
CmpDate: 2022-09-13

Ju Z, Guo P, Xiang J, et al (2022)

Low-dose radiation exaggerates HFD-induced metabolic dysfunction by gut microbiota through PA-PYCR1 axis.

Communications biology, 5(1):945.

Co-exposure of High-fat-diet (HFD) behavior and environmental low-dose radiation (LDR) is common among majority occupational workers, but the synergism of this co-exposure in metabolic health is poorly understood. This study aimed to investigate the impact of gut microbiota and its metabolites on the regulation of HFD accompanied by LDR-associated with metabolic dysfunction and insulin resistance. Here, we reported that Parasutterella was markedly elevated in the gut microbiota of mice in co-exposure of HFD and LDR, accompanied by increased pyrrolidinecarboxylic acid (PA) level in both intestine and plasma. Transplantation of fecal microbiota from mice with co-exposure HFD and LDR with metabolic dysfunction resulted in increased disruption of metabolic dysfunction, insulin resistance and increased PYCR1 (Pyrroline-5-carboxylate reductase 1) expression. Mechanistically, intestinal barrier was damaged more serious in mice with co-exposure of HFD and LDR, leading high PA level in plasma, activating PYCR1 expression to inhibit insulin Akt/mTOR (AKT kinase-transforming protein/Serine threonine-protein kinase) signaling pathway to aggravate HFD-induced metabolic impairments. This study suggests a new avenue for interventions against western diet companied with low dose radiation exposure-driven metabolic impairments.

RevDate: 2022-09-12

Juárez-Fernández M, Goikoetxea-Usandizaga N, Porras D, et al (2022)

Enhanced mitochondrial activity reshapes a gut microbiota profile that delays NASH progression.

Hepatology (Baltimore, Md.) [Epub ahead of print].

BACKGROUND AND AIMS: Recent studies suggest that mitochondrial dysfunction promotes progression to NASH by aggravating the gut-liver status. However, the underlying mechanism remains unclear. Herein, we hypothesized that enhanced mitochondrial activity might reshape a specific microbiota signature that, when transferred to germ-free (GF) mice, could delay NASH progression.

APPROACH AND RESULTS: Wild-type and methylation-controlled J protein knockout (MCJ-KO) mice were fed for 6 weeks with either control or a choline-deficient, L-amino acid-defined, high-fat diet (CDA-HFD). One mouse of each group acted as a donor of cecal microbiota to GF mice, who also underwent the CDA-HFD model for 3 weeks. Hepatic injury, intestinal barrier, gut microbiome, and the associated fecal metabolome were then studied. Following 6 weeks of CDA-HFD, the absence of methylation-controlled J protein, an inhibitor of mitochondrial complex I activity, reduced hepatic injury and improved gut-liver axis in an aggressive NASH dietary model. This effect was transferred to GF mice through cecal microbiota transplantation. We suggest that the specific microbiota profile of MCJ-KO, characterized by an increase in the fecal relative abundance of Dorea and Oscillospira genera and a reduction in AF12, Allboaculum, and [Ruminococcus], exerted protective actions through enhancing short-chain fatty acids, nicotinamide adenine dinucleotide (NAD+) metabolism, and sirtuin activity, subsequently increasing fatty acid oxidation in GF mice. Importantly, we identified Dorea genus as one of the main modulators of this microbiota-dependent protective phenotype.

CONCLUSIONS: Overall, we provide evidence for the relevance of mitochondria-microbiota interplay during NASH and that targeting it could be a valuable therapeutic approach.

RevDate: 2022-09-13
CmpDate: 2022-09-13

Martín Legorburo MJ, Pareja Sierra T, Martínez Ramírez M, et al (2022)

[Fecal transplantation for the treatment of Clostridioides difficile recurrent infection].

Revista espanola de geriatria y gerontologia, 57(4):236-237.

RevDate: 2022-09-13
CmpDate: 2022-09-13

Shaikh FY, Gills JJ, Mohammad F, et al (2022)

Murine fecal microbiota transfer models selectively colonize human microbes and reveal transcriptional programs associated with response to neoadjuvant checkpoint inhibitors.

Cancer immunology, immunotherapy : CII, 71(10):2405-2420.

Human gut microbial species found to associate with clinical responses to immune checkpoint inhibitors (ICIs) are often tested in mice using fecal microbiota transfer (FMT), wherein tumor responses in recipient mice may recapitulate human responses to ICI treatment. However, many FMT studies have reported only limited methodological description, details of murine cohorts, and statistical methods. To investigate the reproducibility and robustness of gut microbial species that impact ICI responses, we performed human to germ-free mouse FMT using fecal samples from patients with non-small cell lung cancer who had a pathological response or nonresponse after neoadjuvant ICI treatment. R-FMT mice yielded greater anti-tumor responses in combination with anti-PD-L1 treatment compared to NR-FMT, although the magnitude varied depending on mouse cell line, sex, and individual experiment. Detailed investigation of post-FMT mouse microbiota using 16S rRNA amplicon sequencing, with models to classify and correct for biological variables, revealed a shared presence of the most highly abundant taxa between the human inocula and mice, though low abundance human taxa colonized mice more variably after FMT. Multiple Clostridium species also correlated with tumor outcome in individual anti-PD-L1-treated R-FMT mice. RNAseq analysis revealed differential expression of T and NK cell-related pathways in responding tumors, irrespective of FMT source, with enrichment of these cell types confirmed by immunohistochemistry. This study identifies several human gut microbial species that may play a role in clinical responses to ICIs and suggests attention to biological variables is needed to improve reproducibility and limit variability across experimental murine cohorts.

RevDate: 2022-09-10

Xu Q, Zhang S, Quan J, et al (2022)

The evaluation of fecal microbiota transplantation vs vancomycin in a Clostridioides difficile infection model.

Applied microbiology and biotechnology [Epub ahead of print].

Vancomycin is the preferred treatment for Clostridioides difficile infection (CDI) but has been associated with a high recurrence rate of CDI in treated patients. Fecal microbiota transplantation (FMT) has emerged as a remarkably successful treatment for recurrent CDI (rCDI). Herein, we present a mouse model of CDI to further define the changes in intestinal inflammation, flora, and metabolites following FMT versus vancomycin treatment and to find the potential therapy to restore colonization resistance. Both FMT and vancomycin treatment could ameliorate CDI-induced clinical features and intestinal tissue damage, with decrease in the levels of inflammatory mediators like IL-1β, IL-6, TNF-α, G-CSF, and MCP-1 in the colon and plasma. Observing the fecal gut microbiome profile revealed that unlike vancomycin, FMT could replenish intestinal microbiota by augmenting the relative abundance of the phylum Bacteroidetes and eliminating the abundance of the phylum Proteobacteria. FMT also reduced the levels of several carbohydrates, such as raffinose and fructose-6-phosphate, and amino acids, including tryptophan and glutamyl-valine, in the gut metabolome, thus suppressing C. difficile germination and growth. Our results suggest that the FMT-induced reconstruction of a specific gut community structure and restoration of metabolites promote the recovery of colonization resistance in mice better than vancomycin, thus offering new insights for the prevention of rCDI. KEY POINTS: • Both FMT and vancomycin ameliorate CDI-induced inflammatory response. • FMT restores a specific community structure and gut metabolites. • Mice treated with FMT may promote the recovery of colonization resistance and has a better outcome.

RevDate: 2022-09-12

Shi C, Zhou L, Li H, et al (2022)

Intestinal microbiota metabolizing Houttuynia cordata polysaccharides in H1N1 induced pneumonia mice contributed to Th17/Treg rebalance in gut-lung axis.

International journal of biological macromolecules, 221:288-302 pii:S0141-8130(22)01937-7 [Epub ahead of print].

Influenza A virus is intricately linked to dysregulation of gut microbiota and host immunity. Previous study revealed that Houttuynia cordata polysaccharides (HCP) exert the therapeutic effect on influenza A virus inducing lung and intestine damage via regulating pulmonary and intestinal mucosal immunity. However, whether this result was due to the regulation of gut microbiota in the gut-lung axis remains unclear. Here, we firstly found that the elimination of gut microbiota using antibiotic cocktails led to both loss of the protective effect of HCP on intestine and lung injury, and reduction of the efficacy on regulating Th17/Treg balance in gut-lung axis. Fecal microbiota transplantation study confirmed that the gut microbiota fermented with HCP under pathological conditions (H1N1 infection) was responsible for reducing pulmonary and intestinal injury. Moreover, the interaction of HCP and gut microbiota under pathological conditions exhibited not only much more abundant gut microbial diversity, but also higher content of the acetate. Our results demonstrated that the underlying mechanism to ameliorate viral pneumonia in mice involving Th17/Treg rebalance via the gut microbiota and HCP metabolite (acetate) metabolized in pneumonia mice. Our results provided a new insight for macromolecular polysaccharides through targeting intestinal microenvironment reducing distant pulmonary infection.

RevDate: 2022-09-09

Luo Y, Wang J, Wang C, et al (2022)

The fecal arsenic excretion, tissue arsenic accumulation, and metabolomics analysis in sub-chronic arsenic-exposed mice after in situ arsenic-induced fecal microbiota transplantation.

The Science of the total environment pii:S0048-9697(22)05682-0 [Epub ahead of print].

Arsenic can be specifically enriched by rice, and the health hazards caused by high arsenic rice are gradually attracting attention. This study aimed to explore the potential of microbial detoxification via gut microbiome in the treatment of sub-chronic arsenic poisoning. We first exposed mice to high-dose arsenic feed (30 mg/kg, rice arsenic composition) for 60 days to promote arsenic-induced microbes in situ in the gastrointestinal tract, then transplanted their fecal microbiota (FMT) into another batch of healthy recipient mice, and dynamically monitored the microbial colonization by 16S rRNA sequencing and ITS sequencing. The results showed that in situ arsenic-induced fecal microbiome can stably colonized and interact with indigenous microbes in the recipient mice in two weeks, and established a more stable network of gut microbiome. Then, the recipient mice continued to receive high-dose arsenic exposure for 52 days. After above sub-chronic arsenic exposure, compared with the non-FMT group, fecal arsenic excretion, liver and plasma arsenic accumulation were significantly lower (P < 0.05), and that in kidney, hair, and thighbone present no significant differences. Metabolomics of feces- plasma-brain axis were also disturbed, some up-regulated metabolites in feces, plasma, and cerebral cortex may play positive roles for the host. Therefore, microbial detoxification has potential in the treatment of sub-chronic arsenic poisoning. However, gut flora is an extremely complex community with different microorganisms have different arsenic metabolizing abilities, and various microbial metabolites. Coupled with the matrix effects, these factors will have various effects on the efflux and accumulation of arsenic. The definite effects (detoxification or non-detoxification) could be not assured based on the current study, and more systematic and rigorous studies are needed in the future.

RevDate: 2022-09-09

Kong B, Fu H, Xiao Z, et al (2022)

Gut microbiota dysbiosis induced by a high-fat diet increases susceptibility to atrial fibrillation.

The Canadian journal of cardiology pii:S0828-282X(22)00786-3 [Epub ahead of print].

BACKGROUND: Obesity is a significant risk factor for atrial fibrillation (AF), and the gut microbiota is closely related to obesity-induced diseases. However, whether the gut microbiota is involved in regulating obesity-induced AF has not been studied. This study investigated whether gut microbiota dysbiosis affects obesity-related AF.

METHODS: Fecal microbes derived from normal diet (ND)-fed and high-fat diet (HD)-fed mice were transplanted into those fed normally. Morphological, biochemical, functional, histological, electrophysiological studies, molecular analysis, 16S rRNA gene amplicon sequencing, and RNA-sequencing were performed.

RESULTS: Transplantation of the HD gut microbes in ND-maintained (THD) mice led to a significant increase in the susceptibility to AF. Gut microbiota analysis showed a significant increase in Desulfovibrionaceae, which generated metabolic endotoxemia in THD mice. Transplantation with HD microbes also resulted in significantly increased levels of circulating lipopolysaccharide (LPS), significant disruption in the histological architecture of the intestinal tissue, and significantly increased pro-inflammatory cytokines in the left atrium, indicating that atrial inflammation likely contributed to AF susceptibility. RNA-sequencing showed that the THD group had enhanced activation of ferroptosis and TLR4/NF-κB/NLRP3 inflammasome signaling pathway. Inhibiting the ferroptosis or NLRP3 inflammasome signaling pathway significantly improved atrial fibrosis and reduced susceptibility to obesity-related gut dysbiosis-induced AF.

CONCLUSIONS: This study provides evidence showing an original causal role of gut microbiota dysbiosis in the pathogenesis of obesity-related AF, which showed elevated LPS and dysregulation of atrial pathological remodeling by activating ferroptosis and the TLR4/NF-κB/NLRP3 inflammasome signaling pathway.

RevDate: 2022-09-12
CmpDate: 2022-09-12

Zheng Z, Wang S, Wu C, et al (2022)

Gut Microbiota Dysbiosis after Traumatic Brain Injury Contributes to Persistent Microglial Activation Associated with Upregulated Lyz2 and Shifted Tryptophan Metabolic Phenotype.

Nutrients, 14(17): pii:nu14173467.

Traumatic brain injury (TBI) is a common cause of disability and mortality, affecting millions of people every year. The neuroinflammation and immune response post-TBI initially have neuroprotective and reparative effects, but prolonged neuroinflammation leads to secondary injury and increases the risk of chronic neurodegenerative diseases. Persistent microglial activation plays a critical role in chronic neuroinflammation post-TBI. Given the bidirectional communication along the brain-gut axis, it is plausible to suppose that gut microbiota dysbiosis post-TBI influences microglial activation. In the present study, hippocampal microglial activation was observed at 7 days and 28 days post-TBI. However, in TBI mice with a depletion of gut microbiota, microglia were activated at 7 days post-TBI, but not at 28 days post-TBI, indicating that gut microbiota contributes to the long-term activation of microglia post-TBI. In addition, in conventional mice colonized by the gut microbiota of TBI mice using fecal microbiota transplant (FMT), microglial activation was observed at 28 days post-TBI, but not at 7 days post-TBI, supporting the role of gut microbiota dysbiosis in persistent microglial activation post-TBI. The RNA sequencing of the hippocampus identified a microglial activation gene, Lyz2, which kept upregulation post-TBI. This persistent upregulation was inhibited by oral antibiotics and partly induced by FMT. 16s rRNA gene sequencing showed that the composition and function of gut microbiota shifted over time post-TBI with progressive dysbiosis, and untargeted metabolomics profiling revealed that the tryptophan metabolic phenotype was differently reshaped at 7 days and 28 days post-TBI, which may play a role in the persistent upregulation of Lyz2 and the activation of microglia. This study implicates that gut microbiota and Lyz2 are potential targets for the development of novel strategies to address persistent microglial activation and chronic neuroinflammation post-TBI, and further investigations are warranted to elucidate the specific mechanism.

RevDate: 2022-09-12

Lanthier N, N Delzenne (2022)

Targeting the Gut Microbiome to Treat Metabolic Dysfunction-Associated Fatty Liver Disease: Ready for Prime Time?.

Cells, 11(17): pii:cells11172718.

Numerous studies show a modification of the gut microbiota in patients with obesity or diabetes. Animal studies have also shown a causal role of gut microbiota in liver metabolic disorders including steatosis whereas the human situation is less clear. Patients with metabolic dysfunction associated fatty liver disease (MAFLD) also have a modification in their gut microbiota composition but the changes are not fully characterized. The absence of consensus on a precise signature is probably due to disease heterogeneity, possible concomitant medications and different selection or evaluation criteria. The most consistent changes were increased relative abundance of Proteobacteria, Enterobacteriaceae and Escherichia species and decreased abundance of Coprococcus and Eubacterium. Possible mechanisms linking the microbiota and MAFLD are increased intestinal permeability with translocation of microbial products into the portal circulation, but also changes in the bile acids and production of microbial metabolites such as ethanol, short chain fatty acids and amino acid derivatives able to modulate liver metabolism and inflammation. Several interventional studies exist that attempt to modulate liver disease by administering antibiotics, probiotics, prebiotics, synbiotics, postbiotics or fecal transplantation. In conclusion, there are both gaps and hopes concerning the interest of gut microbiome evaluation for diagnosis purposes of MAFLD and for new therapeutic developments that are often tested on small size cohorts.

RevDate: 2022-09-12
CmpDate: 2022-09-12

Hu ML, Lian WS, Wang FS, et al (2022)

Presume Why Probiotics May Not Provide Protection in Inflammatory Bowel Disease through an Azoxymethane and Dextran Sodium Sulfate Murine Model.

International journal of molecular sciences, 23(17): pii:ijms23179689.

Recent studies have shown dysbiosis is associated with inflammatory bowel disease (IBD). However, trying to restore microbial diversity via fecal microbiota transplantation (FMT) or probiotic intervention fails to achieve clinical benefit in IBD patients. We performed a probiotic intervention on a simulated IBD murine model to clarify their relationship. IBD was simulated by the protocol of azoxymethane and dextran sodium sulfate (AOM/DSS) to set up a colitis and colitis-associated neoplasm model on BALB/c mice. A single probiotic intervention using Clostridium butyricum Miyairi (CBM) on AOM/DSS mice to clarify the role of probiotic in colitis, colitis-associated neoplasm, gut microbiota, and immune cytokines was performed. We found dysbiosis occurred in AOM/DSS mice. The CBM intervention on AOM/DSS mice failed to improve colitis and colitis-associated neoplasms but changed microbial composition and unexpectedly increased expression of proinflammatory IL-17A in rectal tissue. We hypothesized that the probiotic intervention caused dysbiosis. To clarify the result, we performed inverse FMT using feces from AOM/DSS mice to normal recipients to validate the pathogenic effect of dysbiosis from AOM/DSS mice and found mice on inverse FMT did develop colitis and colon neoplasms. We presumed the probiotic intervention to some extent caused dysbiosis as inverse FMT. The role of probiotics in IBD requires further elucidation.

RevDate: 2022-09-12
CmpDate: 2022-09-12

D'Antonio DL, Marchetti S, Pignatelli P, et al (2022)

The Oncobiome in Gastroenteric and Genitourinary Cancers.

International journal of molecular sciences, 23(17): pii:ijms23179664.

Early evidence suggests a strong association of microorganisms with several human cancers, and great efforts have been made to understand the pathophysiology underlying microbial carcinogenesis. Bacterial dysbiosis causes epithelial barrier failure, immune dysregulation and/or genotoxicity and, consequently, creates a tumor-permissive microenvironment. The majority of the bacteria in our body reside in the gastrointestinal tract, known as gut microbiota, which represents a complex and delicate ecosystem. Gut microbes can reach the pancreas, stomach and colon via the bloodstream. Oral bacterial translocations can also occur. In the stomach, pancreas and colon, low microbial diversity is associated with cancer, in particular with a bad prognosis. The urogenital tract also harbors unique microbiota, distinct from the gut microbiota, which might have a role in the urinary and female/male reproductive cancers' pathogenesis. In healthy women, the majority of bacteria reside in the vagina and cervix and unlike other mucosal sites, the vaginal microbiota exhibits low microbial diversity. Genital dysbiosis might have an active role in the development and/or progression of gynecological malignancies through mechanisms including modulation of oestrogen metabolism. Urinary dysbiosis may influence the pathogenesis of bladder cancer and prostate cancer in males. Modulation of the microbiome via pre, pro and postbiotics, fecal or vaginal microbiota transplantation and engineering bacteria might prove useful in improving cancer treatment response and quality of life. Elucidating the complex host-microbiome interactions will result in prevention and therapeutic efficacy interventions.

RevDate: 2022-09-08

Cheng J, Zhang X, Zhang D, et al (2022)

Sheep fecal transplantation affects growth performance in mouse models by altering gut microbiota.

Journal of animal science pii:6694243 [Epub ahead of print].

Animal growth traits are important and complex traits that determine the productivity of animal husbandry. There are many factors that affect growth traits, among which diet digestion is the key factor. In the process of animal digestion and absorption, the role of gastrointestinal microbes is essential. In this study, we transplanted two groups of sheep intestinal microorganisms with different body weight into the intestines of mice of the same age to observe the effect of fecal bacteria transplantation on the growth characteristics of the mouse model. The results showed that receiving FMT had a effect on the growth traits of recipient mice (p < 0.05). Interestingly, only mice receiving high-weight donor microorganisms showed differences. Use 16S rDNA sequencing technology to analyze the stool microorganisms of sheep and mice. The microbial analysis of mouse feces showed that receiving FMT could improve the diversity and richness of microorganisms (p < 0.05), and the microbial composition of mouse feces receiving low-weight donor microorganisms was similar to that of the control group, which was consistent with the change trend of growth traits. The feces of high-weight sheep may have higher colonization ability. The same five biomarkers were identified in the donor and recipient, all belonging to Firmicutes, and were positively correlated with the body weight of mice at each stage. These results suggest that FMT affects the growth traits of receptors by remodeling their gut microflora.

RevDate: 2022-09-08

Piazzesi A, L Putignani (2022)

Extremely small and incredibly close: Gut microbes as modulators of inflammation and targets for therapeutic intervention.

Frontiers in microbiology, 13:958346.

Chronic inflammation is a hallmark for a variety of disorders and is at least partially responsible for disease progression and poor patient health. In recent years, the microbiota inhabiting the human gut has been associated with not only intestinal inflammatory diseases but also those that affect the brain, liver, lungs, and joints. Despite a strong correlation between specific microbial signatures and inflammation, whether or not these microbes are disease markers or disease drivers is still a matter of debate. In this review, we discuss what is known about the molecular mechanisms by which the gut microbiota can modulate inflammation, both in the intestine and beyond. We identify the current gaps in our knowledge of biological mechanisms, discuss how these gaps have likely contributed to the uncertain outcome of fecal microbiota transplantation and probiotic clinical trials, and suggest how both mechanistic insight and -omics-based approaches can better inform study design and therapeutic intervention.

RevDate: 2022-09-08

Liu JY, Lin TL, Chiu CY, et al (2022)

Decolonization of carbapenem-resistant Klebsiella pneumoniae from the intestinal microbiota of model mice by phages targeting two surface structures.

Frontiers in microbiology, 13:877074.

Background: Klebsiella pneumoniae is a normal component of the human gastrointestinal tract microbiota. However, in some cases, it can cause disease. Over the past 20 years, the prevalence of antibiotic-resistant bacteria, such as carbapenem-resistant K. pneumoniae (CRKP), has been increasing.

Materials and methods: We attempted to specifically eliminate CRKP from a mouse model with the human intestinal microbiota. To establish humanized microbiota-colonized mice, we administered K64 CRKP-containing human microbiota to germ-free mice by fecal microbiota transplantation. Then, we used two phages, one targeting the capsule (φK64-1) and one targeting O1 lipopolysaccharide (φKO1-1) of K64 K. pneumoniae, to eliminate CRKP.

Results: In untreated control and φKO1-1-treated K64-colonized mice, no change in CRKP was observed, while in mice treated with φK64-1, a transient reduction was observed. In half of the mice treated with both φKO1-1 and φK64-1, CRKP was undetectable in feces by PCR and culture for 60 days. However, in the other 50% of the mice, K. pneumoniae was transiently reduced but recovered 35 days after treatment.

Conclusion: Combination treatment with φK64-1 and φKO1-1 achieved long-term decolonization in 52.3% of mice carrying CRKP. Importantly, the composition of the intestinal microbiota was not altered after phage treatment. Therefore, this strategy may be useful not only for eradicating drug-resistant bacterial species from the intestinal microbiota but also for the treatment of other dysbiosis-associated diseases.

RevDate: 2022-09-09
CmpDate: 2022-09-09

Tchitchek N, Nguekap Tchoumba O, Pires G, et al (2022)

Low-dose IL-2 shapes a tolerogenic gut microbiota that improves autoimmunity and gut inflammation.

JCI insight, 7(17): pii:159406.

Gut microbiota dysbiosis is associated with inflammatory bowel diseases and with cardiometabolic, neurological, and autoimmune diseases. Gut microbiota composition has a direct effect on the immune system, and vice versa, and it has a particular effect on Treg homeostasis. Low-dose IL-2 (IL-2LD) stimulates Tregs and is a promising treatment for autoimmune and inflammatory diseases. We aimed to evaluate the impact of IL-2LD on gut microbiota and correlatively on the immune system. We used 16S ribosomal RNA profiling and metagenomics to characterize gut microbiota of mice and humans treated or not with IL-2LD. We performed fecal microbiota transplantation (FMT) from IL-2LD-treated to naive recipient mice and evaluated its effects in models of gut inflammation and diabetes. IL-2LD markedly affected gut microbiota composition in mice and humans. Transfer of an IL-2-tuned microbiota by FMT protected C57BL/6J mice from dextran sulfate sodium-induced colitis and prevented diabetes in NOD mice. Metagenomic analyses highlighted a role for several species affected by IL-2LD and for microbial pathways involved in the biosynthesis of amino acids, short-chain fatty acids, and L-arginine. Our results demonstrate that IL-2LD induced changes in gut microbiota that are involved in the immunoregulatory effects of IL-2LD and suggest a crosstalk between Tregs and gut microbiota. These results provide potentially novel insight for understanding the mode of action of Treg-directed therapies.

RevDate: 2022-09-08
CmpDate: 2022-09-08

Lu G, Wang W, Li P, et al (2022)

Washed preparation of faecal microbiota changes the transplantation related safety, quantitative method and delivery.

Microbial biotechnology, 15(9):2439-2449.

The safety, quantitative method and delivery of faecal microbiota transplantation (FMT) vary a lot from different countries in practice. Recently, the improved methodology of FMT based on the automatic filtration, washing process and the related delivery was named as washed microbiota transplantation (WMT). First, this study aimed to describe the methodology development of FMT from manual to washing preparation from 2012 to 2021 in China Microbiota Transplantation System (CMTS), a centralized stool bank for providing a national non-profit service. The secondary aim is to describe donor screenings, the correlation between faecal weight and treatment doses, incidence of adverse events and delivery decision. The retrospective analysis on the prospectively recorded data was performed. Results showed that the success rate of donor screening was 3.1% (32/1036). The incidence rate of fever decreased significantly from 19.4% (6/31) in manual FMT to 2.7% (24/902) in WMT in patients with ulcerative colitis (UC), which made UC a considerable disease model to reflect the quality control of faecal microbiota preparation. We defined one treatment unit as 10 cm3 microbiota precipitation (1.0 × 1013 bacteria) based on enriched microbiota instead of rough faecal weight. For delivering microbiota, colonic transendoscopic enteral tube is a promising way especially for multiple WMTs or frequent colonic administration of drugs combined with WMT. This study should help improve the better practice of FMT for helping more patients in the future.

RevDate: 2022-09-08
CmpDate: 2022-09-08

Parker G, Spoelma MJ, N Rhodes (2022)

Faecal microbiota transplantation for bipolar disorder: A detailed case study.

Bipolar disorders, 24(5):559-563.

RevDate: 2022-09-07
CmpDate: 2022-09-07

Alberca GGF, Cardoso NSS, Solis-Castro RL, et al (2022)

Intestinal inflammation and the microbiota: Beyond diversity.

World journal of gastroenterology, 28(26):3274-3278.

The recent manuscript entitled "Relationship between clinical features and intestinal microbiota in Chinese patients with ulcerative colitis" reported a difference in the intestinal microbiota of patients with ulcerative colitis according to the severity of the colitis. The influence of the intestinal microbiota on the development and progress of gastrointestinal disorders is well established. Besides the diversity in the microbiome, the presence of virulence factors and toxins by commensal bacteria may affect an extensive variety of cellular processes, contributing to the induction of a proinflammatory environment.

RevDate: 2022-09-06

Wang JG, Liang Q, Dou HH, et al (2022)

The Global Incidence of Adverse Events Associated with Fecal Microbiota Transplantation in Children over the Past 20 Years: A Systematic Review and Meta-Analysis.

Journal of gastroenterology and hepatology [Epub ahead of print].

OBJECTIVES: To understand the global incidence of the adverse events associated with fecal microbiota transplantation (FMT) in children over the past 20 years.

METHODS: We searched PubMed, Web of Science, Embase, and three Chinese databases (CNKI, Wanfang, and Chongqing Weipu) for high-quality articles written over the past 20 years and made selections based on the quality standard score. The study characteristics and incidences of adverse events were extracted from each article, meta-analysis was performed using the R.3.6.3 software, and randomized- or fixed-effect meta-analyses were used to determine the incidence of adverse events. Subgroup analysis was performed to determine heterogeneity.

RESULTS: A total of 18 articles involving 681 children were included in the analysis. The total effective rate of FMT in children was 85.75% (95% CI: 76.23-93.15 %), of which the overall efficacy of FMT for the treatment of Clostridium difficile infection was 91.22% (95% CI: 83.49-96.68 %) and the overall adverse event rate was 28.86% (95% CI:19.56-39.15 %) .with a mild to moderate adverse event rate of 27.72% (95% CI: 17.86-38.83 %) and a severe adverse event rate of 0.90% (95% CI: 0.33-1.76 %). The most common mild to moderate adverse events were as follows: Bellyache, 14.02% (95% CI: 5.43-25.77 %); diarrhea, 7.75% (95% CI: 2.69-15.11 %); and bloating, 7.36% (95% CI: 1.79-16.28 %). Other adverse events included fever, 2.34%; vomiting, 3.12%; nausea, 1.50%; hematochezia, 2.30%; anorexia, 1.94%; and fatigue, 0.03%. The only death reported was in a study from China, in which the patient died of sepsis and liver failure four weeks after FMT. The other serious adverse event was an immunodeficiency patient with severe hematochezia. Another study in the United States described seven serious adverse events including one death which was not considered to be related to FMT; however, they did not describe the events in detail. There was no difference in the incidence of adverse events between the upper and lower gastrointestinal tracts (OR = 0.61, 95% CI: 0.02-15.42 , P = 0.76).

CONCLUSION: Adverse events related to FMT in children are mostly mild to moderate, of short duration, and self-limiting. Therefore, the use of FMT in children is safe and worthy of widespread promotion.

RevDate: 2022-09-06

Wang M, Xie X, Zhao S, et al (2022)

Global research trends and hotspots of fecal microbiota transplantation: A bibliometric and visualization study.

Frontiers in microbiology, 13:990800.

Introduction: Fecal microbiota transplantation (FMT) has gained considerable attention in a variety of clinical research areas, and an increasing number of articles are being published. It is very critical to reveal the global status, future research trends, and hotspots in the FMT research and application.

Methods: We searched the Web of Science Core Collection up to May 10, 2022, and only articles and review articles about FMT were included finally. CiteSpace 5.8.R3, VOSviewer 1.6.18, Scimago Graphica and Microsoft Office Excel 2019 were used for data analysis and visualization. The results included publication characteristics, Co-authorships analysis, Co-cited analysis, Co-occurrence analysis, and burst analysis.

Results: Eleven thousand nine hundred seventy-two records were used for the analysis and visualization finally, these records were published between 1980 and 2022, and the publication about FMT is increasing year by year. Co-authorship analysis shown that the USA played a key role in this field. After data analysis and visualization, a total of 57 hotspots about FMT were produced. We summarized these hotspots and classified them into 7 grades according to the number of evidence sources. The evidence sources included top 25 of Web of Science categories, top 30 most Co-cited references, top 10 clusters of references, top 25 references with the strongest citation bursts, top 25 keywords with the most occurrence frequency, major 15 clusters of keywords, top 25 keywords with the strongest citation bursts, and top 35 disease keywords.

Conclusion: This bibliometric analysis is expected to provide overall perspective for FMT. FMT has gained increasing attention and interest, there are many hotspots in this field, which may help researchers to explore new directions for future research.

RevDate: 2022-09-03

Hole MJ, Kaasen Jørgensen K, Holm K, et al (2022)

A shared mucosal gut microbiota signature in primary sclerosing cholangitis before and after liver transplantation.

Hepatology (Baltimore, Md.) [Epub ahead of print].

BACKGROUND AND AIMS: Several characteristic features of the fecal microbiota have been described in primary sclerosing cholangitis (PSC), while data on mucosal microbiota are less consistent. We aimed to utilize a large colonoscopy cohort to investigate key knowledge gaps, including the role of gut microbiota in PSC with inflammatory bowel disease (IBD), the effect of liver transplantation (LT), and whether recurrent PSC (rPSC) may be used to define consistent microbiota features in PSC irrespective of LT.

APPROACH AND RESULTS: We included 84 PSC and 51 liver transplanted PSC patients (PSC-LT), and 40 healthy controls (HC) and performed sequencing of the 16S rRNA gene (V3-V4) from ileocolonic biopsies. The intra-individual microbial diversity was reduced in both PSC and PSC-LT vs. HC. An expansion of Proteobacteria was more pronounced in PSC-LT (up to 19% relative abundance) than in PSC (up to 11%) and HC (up to 8%), (QFDR < 0.05). When investigating PSC before (PSC vs. HC) and after LT (rPSC vs. no-rPSC), increased variability (dispersion) in the PSC group was found. Five genera associated with PSC before and after LT. A dysbiosis index calculated from the five genera, and the presence of the potential pathobiont Klebsiella associated with reduced LT-free survival. Concomitant IBD was associated with reduced Akkermansia.

CONCLUSION: Consistent mucosal microbiota features associated with PSC, PSC-IBD and disease severity, irrespective of LT status, highlights the utility of investigating PSC and rPSC in parallel, and suggests that the impact of gut microbiota on post-transplant liver health should be investigated further.

RevDate: 2022-09-02

Wang Q, Guo X, Yue Q, et al (2022)

Exploring the role and mechanism of gut microbiota in methamphetamine addiction using antibiotic treatment followed by fecal microbiota transplantation.

Anatomical record (Hoboken, N.J. : 2007) [Epub ahead of print].

Recently, the role of the gut microbiota in the context of drug addiction has attracted the attention of researchers; however, the specific effects and underlying mechanisms require further exploration. To accomplish this, C57BL/6 mice were firstly treated with methamphetamine (MA). Conditioned place preference (CPP) behavior changes, gut permeability and function, microglial activation, and inflammatory cytokine expression were systematically analyzed in antibiotics-treated mice with microbiota depletion and in fecal microbiota transplantation mice with microbiota reconstitution. MA treatment altered microbiota composition and caused gut dysbiosis. Depletion of gut microbiota with antibiotics inhibited MA-induced CPP formation, and fecal microbiota transplantation reversed this inhibition. Mechanistic analyses indicated that antibiotic treatment decreased gut permeability and neuroinflammation, while fecal microbiota transplantation offset the impact of antibiotic treatment. Additionally, MA-induced microglial activation was suppressed by antibiotics but restored by microbiota transplantation, and this correlated well with the CPP score. Compared to antibiotic treatment, microbiota transplantation significantly increased 5-HT4 receptor expression in both the nucleus accumbens and the hippocampus. Furthermore, when fecal microbiota from healthy mice was transplanted into MA-treated mice, the CPP scores decreased. Our results provide a novel avenue for understanding MA addiction and suggest a potential future intervention strategy.

RevDate: 2022-09-02

Stallmach A, Steube A, Stallhofer J, et al (2022)

[Fecal microbiota transplantation: indications, risks and opportunities].

Innere Medizin (Heidelberg, Germany) [Epub ahead of print].

Fecal microbiome transfer (FMT) involving the transfer of the microbiome of healthy stool donors to patients with various diseases has been performed in Germany in clinical studies and individual treatment attempts. There is no doubt that FMT is an effective therapeutic principle for recurrent Clostridium difficile infection and ulcerative colitis. From a medico-legal point of view, it should be stressed that, in Germany, the microbiome to be transferred is regarded as a drug, the manufacture of which is subject to the Medicines Act and the risk information from the Federal Institute for Drugs and Medical Devices. The background of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and the potential risk of transmitting pathogens must also be considered. There is an obligation to notify the competent state authorities to perform FMTs in the context of individual treatment attempts. In the context of the limited availability and the fundamental problem of infection, future studies aim to identify the therapeutically active components in the microbiome. Recombinant production is the aim. Initial results represent preliminary steps, as these concepts are not yet established in clinical practice.

RevDate: 2022-09-01

Mukohda M, Mizuno R, H Ozaki (2022)

[Gut microflora and metabolic syndrome: new insight into the pathogenesis of hypertension].

Nihon yakurigaku zasshi. Folia pharmacologica Japonica, 157(5):311-315.

Emerging evidences indicate that a microbial imbalance (dysbiosis) is linked to several diseases including metabolic cardiovascular diseases. A fecal microbiota transplantation from hypertensive human donor to germ-free mice caused blood pressure elevation. In addition, there is a report demonstrating that angiotensin II-induced hypertension and vascular dysfunction were attenuated in germ-free mice, suggesting that gut microbiome may mediate development of hypertension. Although detailed mechanism by which the dysbiosis induces an increased blood pressure remains unknown, changes in microbiome may modify host immune systems and induce inflammatory dysfunction in cardiovascular system, resulting in dysregulation of blood pressure. Some cohort studies demonstrated an association between a higher abundance of Streptococcaceae spp. and blood pressure. One recent report demonstrated that an increasing number of gram-positive Streptococcus was found in the feces of adult spontaneously hypertensive rats with an increased intestinal permeability. We hypothesized that increased bacterial toxin levels derived from gut Streptococcus may be a factor inducing blood pressure dysregulation. In this review, we discuss the possible role of microbiome in cardiovascular disease, especially hypertension.

RevDate: 2022-09-01

Chen Y, Lian B, Li P, et al (2022)

Studies on irritable bowel syndrome associated with anxiety or depression in the last 20 years: A bibliometric analysis.

Frontiers in public health, 10:947097.

Irritable bowel syndrome (IBS) associated with anxiety or depression is ubiquitous in clinical practice, and multiple related articles have been published. However, studies that utilize bibliometric analyses to address this topic are rare. In our study, we aimed to reveal research trends in IBS with anxiety or depression. Publications on IBS in relation to anxiety or depression in the last 20 years were obtained from the Web of Science Core Collection (WoSCC). CiteSpace software (5.8.R3) and GraphPad Prism 8 were used to perform bibliometric analysis of authors, countries, institutions, journals, keywords, and references involved in this topic. A total of 2,562 publications from 716 academic journals were included in this study. The majority of publications (n = 833, 32.51%) were from the USA, and the University of California, Los Angeles, contributed the most publications (n = 97, 3.79%). Active cooperations among countries and institutions were observed. Neurogastroenterology and Motility [impact factor (IF) 2020 = 3.598] published the most papers (170 publications, 6.64%), followed by Alimentary Pharmacology Therapeutics (IF 2020 = 8.171; 88 publications; 3.44%). The literatures related to IBS and anxiety or depression were primarily published in journals related to medicine/medical/clinical, neurology/sports/ophthalmology, and molecular/biology/immunology. Cryan JF and Drossman DA, with the largest number of articles (84 publications) and citations (917 citations), respectively, were considered as the most influential authors in this field. A total of 336 co-cited references were divided into 17 clusters, and #1 fecal microbiota transplantation contained most of the documents published in recent years. Moreover, the keyword "psychosocial factor" had the largest burst strength of 13.52, followed by the keyword "gut microbiota" with a burst strength of 11.71. This study shows the research performance of IBS related to anxiety or depression from 2002 to 2021 and helps researchers master the trend in this field, which should receive more attention.

RevDate: 2022-08-31

Kempski J, S Huber (2022)

[Role of the gut microbiome in the pathogenesis and treatment of inflammatory bowel diseases].

Innere Medizin (Heidelberg, Germany) [Epub ahead of print].

Inflammatory bowel diseases (IBD) are systemic diseases that mainly manifest in the gastrointestinal tract. Due to chronically impaired intestinal homeostasis, they often require permanent and in some cases systemic therapy. The exact causes of IBD are largely unknown. It is postulated that these complex diseases arise in genetically susceptible individuals through a misdirected immune response, promoted by barrier defects, environmental toxins, and the gut microbiome. In this regard, the importance of the microbiome and its pathogenic changes (dysbiosis) in the pathogenesis of IBD is increasingly coming into focus. This review article presents the current state of research on the role of the microbiome in the development of IBD. Therapeutic approaches aimed at correcting intestinal dysbiosis are also discussed.

RevDate: 2022-08-31

Tan B, Liu YX, Tang H, et al (2022)

Gut microbiota shed new light on the management of immune-related adverse events.

Thoracic cancer [Epub ahead of print].

Immunotherapy has dramatically revolutionized the therapeutic landscape for patients with cancer. Although immune checkpoint inhibitors are now accepted as effective anticancer therapies, they introduce a novel class of toxicity, termed immune-related adverse events, which can lead to the temporary or permanent discontinuation of immunotherapy and life-threatening tumor progression. Therefore, the effective prevention and treatment of immune-related adverse events is a clinical imperative to maximize the utility of immunotherapies. Immune-related adverse events are related to the intestinal microbiota, baseline gut microbiota composition is an important determinant of immune checkpoint inhibitor-related colitis, and antibiotics exacerbate these undesirable side-effects. Supplementation with specific probiotics reduces immune checkpoint inhibitor-related colitis in mice, and fecal microbiota transplantation has now been shown to effectively treat refractory immune checkpoint inhibitor-related colitis in the clinic. Hence, modifying the microbiota holds great promise for preventing and treating immune-related adverse events. Microbiomes and their metabolites play important roles in the potential underlying mechanisms through interactions with both innate and adaptive immune cells. Here we review the gut microbiota and immune regulation; the changes occurring in the microbiota during immune checkpoint inhibitor therapy; the relationship between the microbiota and immune-related adverse events, antibiotics, probiotics/prebiotics, and fecal microbiota transplantation in immune checkpoint inhibitor-related colitis; and the protective mechanisms mediated by the microbiome and metabolites in immune-related adverse events.

RevDate: 2022-08-30

Jiang H, Peng Y, Zhang W, et al (2022)

Gut microbiome-targeted therapies in liver cirrhosis: a protocol for systematic review and meta-analysis.

Systematic reviews, 11(1):181.

BACKGROUND: Microbiome-targeted therapies (MTTs), including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT), have been proposed as a potential treatment for cirrhosis via modulation of gut microbiome, while the impact of gut microflora alteration on liver function in cirrhosis trajectory is unclear, and no related systematic review has been published. We aim to comprehensively assess the effects of MTTs in patients with liver cirrhosis.

METHODS: We will search databases of MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) with no time restriction. Only randomized controlled trials published in English will be included. Two independent reviewers will be responsible for study identification and selection, data extraction, and risk of bias assessment, with discrepancies resolved by consensus or referral to a third author. Heterogeneity of studies will be examined using Cochrane Q-test and I2 statistics. The data will be pooled using either a fixed- or random-effects model based on I2 statistics. The results will be presented as risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CI). We will perform subgroup analysis on the type of MTTs and assess the reporting biases. Sensitivity analysis will be conducted to test the stability of each outcome result.

DISCUSSION: There is no current study about the role of MTTs in developing the liver function, and the therapeutic effects of MTTs are inconsistent. By investigating the liver-specific indicators when treating with multiple MTTs on course of cirrhosis, our findings will give more conclusive and stronger evidence about the efficacy of MTTs and provide new insight into the action mechanisms of these MTTs.

PROSPERO CRD42021253198.

RevDate: 2022-08-30

Liu Y, Jiang Z, Yang H, et al (2022)

Gui Shao Tea Extracts Inhibit Gastric Cancer Growth in Vitro and in Vivo and Prolong Survival in Nude Mice.

Frontiers in bioscience (Landmark edition), 27(8):250.

BACKGROUND: Gui Shao Tea (GST), a long-aged tea with a Chinese herbal aroma, can treat many stubborn and malignant diseases, according to traditional Chinese medicine. This research aimed to discover and define GST, study the anti-gastric cancer effects of GST extracts and preliminarily elucidate the mechanism of action in the PI3K/Akt signaling pathway and the gut microbiota.

METHODS: GST was analyzed by GC/MS and HPLC. Cell proliferation, the cell cycle and apoptosis were evaluated by a CCK8 assay and flow cytometry. The effects of GST extracts on tumor inhibition and survival time were explored by a gastric cancer xenograft model in nude mice. The PI3K/Akt signaling pathway was assessed by western blotting and immunohistochemistry. Gut microbiota detection and fecal microbiota transplantation were performed to examine whether the tumor inhibition observed in mice was related to gut microbiota changes.

RESULTS: The ingredients in GST, mostly terpenes and their derivatives, were novel and more concentrated than those in tea made from the branches and leaves of the same plant species, Camellia sinensis, picked and produced the same year, while the levels of polyphenols and alkaloids were significantly reduced. In BGC-823, MGC-803, and SGC-7901 gastric cancer cells, GST extracts significantly inhibited proliferation (p = 0.037), induced G0/G1 arrest (p < 0.001) and promoted early apoptosis (p = 0.041). In mice, gastric tumor growth was significantly inhibited in both the high-dose (HTF) and middle-dose (MTF) GST-fed groups. The inhibition rate in the HTF group was 33.77% on Day 14 (p = 0.042), and that in the MTF group was 55.21% on Day 14 (p = 0.002) and 61.6% on Day 28 (p = 0.008). The survival time of MTF group mice was significantly prolonged by 22.2% (p = 0.013). GST extracts inhibited the PI3K/AKT signaling pathway in gastric cancer cells (p = 0.016) and tissues (p = 0.029), downregulated the protein p-Rb and further downregulated E2F1, thereby affecting the cell cycle and proliferation. GST extracts altered the gut microbiota in mice, but these alterations alone were insufficient to inhibit gastric cancer growth.

CONCLUSIONS: We confirmed the anti-gastric cancer effects of GST extracts, which might provide new approaches and methods for research and development of gastric cancer drugs.

RevDate: 2022-08-30
CmpDate: 2022-08-30

Medel-Matus JS, Simpson CA, Ahdoot AI, et al (2022)

Modification of post-traumatic epilepsy by fecal microbiota transfer.

Epilepsy & behavior : E&B, 134:108860.

It has been well established that traumatic brain injury (TBI) modifies the composition of gut microbiome. Epilepsy, which represents one of the common sequelae of TBI, has been associated with dysbiosis. Earlier study showed that the risk of post-traumatic epilepsy (PTE) after lateral fluid percussion injury (LFPI) in rats can be stratified based on pre-existing (i.e., pre-TBI) gut microbiome profile. In the present study, we examined whether fecal microbiota transfer (FMT) from naïve rats with different prospective histories of PTE would affect the trajectory of PTE in recipients. Fecal samples were collected from naïve adult male Sprague-Dawley rats, followed by LFPI. Seven months later, upon four weeks of vide-EEG monitoring (vEEG), the rats were categorized as those with and without PTE. Recipients were subjected to LFPI, followed by FMT from donors with and without impending PTE. Control groups included auto-FMT and no-FMT subjects. Seven month after LFPI, recipients underwent four-week vEEG to detect spontaneous seizures. After completing vEEG, rats of all groups underwent kindling of basolateral amygdala. Fecal microbiota transfer from donors with impending PTE exerted mild-to-moderate pro-epileptic effects in recipients, evident as marginal increase in multiple spontaneous seizure incidence, and facilitation of kindling. Analysis of fecal samples in selected recipients and their respective donors confirmed that FMT modified microbiota in recipients along the donors' lines, albeit without full microbiome conversion. The findings provide further evidence that gut microbiome may actively modulate the susceptibility to epilepsy.

RevDate: 2022-08-29

Rathour D, Shah S, Khan S, et al (2022)

ROLE OF GUT MICROBIOTA IN DEPRESSION: UNDERSTANDING MOLECULAR PATHWAYS, RECENT RESEARCH, AND FUTURE DIRECTION.

Behavioural brain research pii:S0166-4328(22)00349-7 [Epub ahead of print].

Gut microbiota, also known as the "second brain" in humans because of the regulatory role it has on the central nervous system via neuronal, chemical and immune pathways. It has been proven that there exists a bidirectional communication between the gut and the brain. Increasing evidence supports that this crosstalk is linked to the etiology and treatment of depression. Reports suggest that the gut microbiota control the host epigenetic machinery in depression and gut dysbiosis causes negative epigenetic modifications via mechanisms like histone acetylation, DNA methylation and non-coding RNA mediated gene inhibition. The gut microbiome can be a promising approach for the management of depression. The diet and dietary metabolites like kynurenine, tryptophan, and propionic acid also greatly influence the microbiome composition and thereby, the physiological activities. This review gives a bird-eye view on the pathological updates and currently used treatment approaches targeting the gut microbiota in depression.

RevDate: 2022-08-29

Han Q, Deng LR, Zou M, et al (2022)

Anemoside B4 protects against chronic relapsing colitis in mice by modulating inflammatory response, colonic transcriptome and the gut microbiota.

Phytomedicine : international journal of phytotherapy and phytopharmacology, 106:154416 pii:S0944-7113(22)00505-0 [Epub ahead of print].

BACKGROUND: Anemoside B4 (AB4) is reported to prevent acute colitis when given via intraperitoneal injection by two recent studies. However, whether oral AB4 protects against chronic colitis which resembles the clinical phenotype of ulcerative colitis (UC) and its mechanism of action are largely unknown.

PURPOSE: To systemically investigate the effects of oral AB4 against chronic colitis and illustrate the underlying mechanism of action.

METHODS: The preventive, therapeutic, and dose-dependent effects of AB4 against UC were examined in mice with acute or chronic relapsing colitis induced by dextran sulfate sodium (DSS). The inflammatory responses, colonic transcriptome, and 16S rDNA sequencing of the intestinal content of mice were analyzed.

RESULTS: Oral administration of AB4 alleviated disease severity and colon shortening in mice with chronic relapsing colitis in a dose-dependent manner. The effects of AB4 were comparable to those of two positive-control compounds: tofacitinib and berberine. Unlike tofacitinib, AB4 did not have a deleterious effect on DSS-induced splenic swelling and anemia. Furthermore, AB4 inhibited the inflammatory responses of colitis, as evidenced by in-vivo, ex-vivo, and in-vitro studies. Transcriptomics revealed that AB4 treatment reversed the DSS-mediated decrease in the expression of colonic Pelo, B3gat2 and Mir8010. In addition, AB4 reversed DSS-induced alterations in the intestinal microbiome in mice. Through fecal microbiota transplantation, we proved that AB4 partially exerted its anti-colitis effects by modulating the gut microbiota.

CONCLUSIONS: We demonstrated for the first time that AB4 has dose-dependent therapeutic effects against chronic relapsing colitis by modulating the inflammatory response, colonic gene expression, and intestinal microbiota.

RevDate: 2022-08-29

Qiu J, Wu C, Gao Q, et al (2022)

Effect of fecal microbiota transplantation on the TGF-β1/Smad signaling pathway in rats with TNBS-induced colitis.

Annals of translational medicine, 10(15):825.

Background: Traditional treatments for inflammatory bowel disease (IBD) have adverse side effects, and patients who receive such treatments have high recurrence rates. Fecal microbiota transplantation (FMT) has become an increasingly popular therapeutic option for patients with IBD. However, the mechanism by which FMT alleviates this disease remains unclear.

Methods: In this study, a rat model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis was established and used to explore whether the transforming growth factor-beta 1 (TGF-β1)/small mothers against decapentaplegic (Smad) signaling pathway plays a critical role in the FMT alleviation of IBD.

Results: After the FMT intervention, the disease activity index and histologic scores were significantly decreased. In addition, the TGF-β1 expression level in the FMT group was significantly decreased by approximately 0.72-fold relative to the level in the TNBS colitis group, whereas the Smad3, Smad4, and Smad7 expression levels had increased by approximately 1.21, 1.40, and 1.18 folds, respectively. Similarly, SB431542 inhibited the expression of TGF-β1 and promoted the expression of Smad3, Smad4, and Smad7. Further, the serum levels of the inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) were significantly decreased, whereas that of the interferon-gamma (IFN-γ) was not significantly changed after the FMT intervention.

Conclusions: These results suggest that FMT inhibits the TGF-β1/Smad signaling pathway to attenuate inflammation.

RevDate: 2022-08-29

Shi X, Wu H, Liu Y, et al (2022)

Inhibiting vascular smooth muscle cell proliferation mediated by osteopontin via regulating gut microbial lipopolysaccharide: A novel mechanism for paeonol in atherosclerosis treatment.

Frontiers in pharmacology, 13:936677 pii:936677.

Background: Although the gut microbiota is involved in metabolic disease such as atherosclerosis, the underlying mechanism remains elusive. Paeonol (Pae) is a natural phenolic compound isolated from Cortex Moutan, which exhibits anti-atherosclerotic effects. Our previous research demonstrated gut microbiota as a site of Pae action. However, the mechanism by which Pae exerts its anti-atherosclerotic effect by the regulation of gut microbiota remains unclear. Objective: To investigate a potential mechanistic link between the gut microbial lipopolysaccharide (LPS) and vascular smooth muscle cell (VSMC) proliferation in atherosclerosis progression and explore the possible role of Pae. Methods: Experimental atherosclerosis was established in ApoE-/- mice, and the atherosclerosis mice were treated with Pae for 4 weeks before being sacrificed for analyses while conducting fecal microbiota transplantation (FMT). The plaque area, levels of serum LPS, expressions of inflammatory factors in serum or aorta, and intestinal barrier permeability were determined. VSMCs were co-cultured with THP-1 cells. CCK-8 assay and EdU staining were performed to assess the proliferative capacity of VSMCs. Immunofluorescence staining was performed to observe the nuclear transfer of p65. Western blotting was used to detect the candidate protein expression level, and quantitative real-time PCR (qRT-PCR) was used to detect the mRNA expression level in tissues or cells of each group. Results: During atherosclerosis progression, gut dysbiosis leads to the peripheral accumulation of gut microbial LPS, which acts as a trigger to stimulate osteopontin (OPN) production from circulating monocytes, inducing cell-to-cell crosstalk to promote VSMC proliferation in the aorta. Importantly, the elevation of LPS and OPN concentrations in the blood was also observed in patients with atherosclerosis. Pae could significantly improve atherosclerosis, suppress gut microbial LPS accumulation, and inhibit monocyte/macrophage activation and VSMC proliferation. Conclusions: The present study provides a mechanistic scenario for how long-term stimulation of gut microbial LPS in circulating blood generates a pathological secondary response that leads to abnormal proliferation of VSMCs using high OPN expression in circulating monocytes and suggests a novel strategy for atherosclerosis therapy by remodeling the gut microbiota.

RevDate: 2022-08-29

Cui C, Han Y, Li H, et al (2022)

Curcumin-driven reprogramming of the gut microbiota and metabolome ameliorates motor deficits and neuroinflammation in a mouse model of Parkinson's disease.

Frontiers in cellular and infection microbiology, 12:887407.

Background: Parkinson's disease (PD) is a common neurodegenerative disorder, accompanied by motor deficits as well as gastrointestinal dysfunctions. Recent studies have proved that the disturbance of gut microbiota and metabolism contributes to the pathogenesis of PD; however, the mechanisms underlying these effects have yet to be elucidated. Curcumin (CUR) has been reported to provide neuroprotective effects on neurological disorders and modulate the gut flora in intestinal-related diseases. Therefore, it is of significant interest to investigate whether CUR could exert a protective effect on PD and whether the effect of CUR is dependent on the intestinal flora and subsequent changes in metabolites.

Methods: In this study, we investigated the neuroprotective effects of CUR on a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). 16S rRNA sequencing was performed to explore the profile of the gut microbiota among controls, MPTP-treated mice and CUR-treated mice. Then, antibiotic treatment (ABX) and fecal microbiota transplantation (FMT) experiments were conducted to examine the role of intestinal microbes on the protective effects of CUR in PD mice. Furthermore, ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS)-based metabolomics analysis was used to identify the landscape of the CUR-driven serum metabolome. Finally, Pearson's analysis was conducted to investigate correlations between the gut flora-metabolite axis and CUR-driven neuroprotection in PD.

Results: Our results showed that CUR intervention effectively improved motor deficits, glial cell activation, and the aggregation of α-synuclein (α-syn) in MPTP-treated mice. 16S rRNA sequencing showed elevated abundances of Muribaculaceae, Lactobacillaceae, Lachnospiraceae and Eggerthellaceae but depleted abundances of Aerococcaceae and Staphylococcaceae in CUR-treated mice when compared with MPTP mice. ABX and FMT experiments further confirmed that the gut microbiota was required for CUR-induced protection in PD mice. Serum metabolomics analysis showed that CUR notably upregulated the levels of tyrosine, methionine, sarcosine and creatine. Importantly, strong correlations were identified among crucial taxa (Aerococcaceae, Staphylococcaceae, Muribaculaceae, Lactobacillaceae, Lachnospiraceae and Eggerthellaceae), pivotal metabolites (tyrosine, methionine, sarcosine and creatine) and the motor function and pathological results of mice. CUR treatment led to a rapid increase in the brain levels of tyrosine and levodopa (dopa) these changes were related to the abundances of Lactobacillaceae and Aerococcaceae.

Conclusions: CUR exerts a protective effect on the progression of PD by modulating the gut microbiota-metabolite axis. Lactobacillaceae and Aerococcaceae, along with key metabolites such as tyrosine and dopa play a dominant role in CUR-associated neuroprotection in PD mice. Our findings offer unique insights into the pathogenesis and potential treatment of PD.

RevDate: 2022-08-29

Wang Z, Li Y, Liao W, et al (2022)

Gut microbiota remodeling: A promising therapeutic strategy to confront hyperuricemia and gout.

Frontiers in cellular and infection microbiology, 12:935723.

The incidence of hyperuricemia (HUA) and gout continuously increases and has become a major public health problem. The gut microbiota, which colonizes the human intestine, has a mutually beneficial and symbiotic relationship with the host and plays a vital role in the host's metabolism and immune regulation. Structural changes or imbalance in the gut microbiota could cause metabolic disorders and participate in the synthesis of purine-metabolizing enzymes and the release of inflammatory cytokines, which is closely related to the occurrence and development of the metabolic immune disease HUA and gout. The gut microbiota as an entry point to explore the pathogenesis of HUA and gout has become a new research hotspot. This review summarizes the characteristics of the gut microbiota in patients with HUA and gout. Meanwhile, the influence of different dietary structures on the gut microbiota, the effect of the gut microbiota on purine and uric acid metabolism, and the internal relationship between the gut microbiota and metabolic endotoxemia/inflammatory factors are explored. Moreover, the intervention effects of probiotics, prebiotics, and fecal microbial transplantation on HUA and gout are also systematically reviewed to provide a gut flora solution for the prevention and treatment of related diseases.

RevDate: 2022-08-29

Liu L, Zhang J, Cheng Y, et al (2022)

Gut microbiota: A new target for T2DM prevention and treatment.

Frontiers in endocrinology, 13:958218.

Type 2 diabetes mellitus (T2DM), one of the fastest growing metabolic diseases, has been characterized by metabolic disorders including hyperglycemia, hyperlipidemia and insulin resistance (IR). In recent years, T2DM has become the fastest growing metabolic disease in the world. Studies have indicated that patients with T2DM are often associated with intestinal flora disorders and dysfunction involving multiple organs. Metabolites of the intestinal flora, such as bile acids (BAs), short-chain fatty acids (SCFAs) and amino acids (AAs)may influence to some extent the decreased insulin sensitivity associated with T2DM dysfunction and regulate metabolic as well as immune homeostasis. In this paper, we review the changes in the gut flora in T2DM and the mechanisms by which the gut microbiota modulates metabolites affecting T2DM, which may provide a basis for the early identification of T2DM-susceptible individuals and guide targeted interventions. Finally, we also highlight gut microecological therapeutic strategies focused on shaping the gut flora to inform the improvement of T2DM progression.

RevDate: 2022-08-29

Gang J, Wang H, Xue X, et al (2022)

Microbiota and COVID-19: Long-term and complex influencing factors.

Frontiers in microbiology, 13:963488.

The coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). According to the World Health Organization statistics, more than 500 million individuals have been infected and more than 6 million deaths have resulted worldwide. Although COVID-19 mainly affects the respiratory system, considerable evidence shows that the digestive, cardiovascular, nervous, and reproductive systems can all be involved. Angiotensin-converting enzyme 2 (AEC2), the target of SARS-CoV-2 invasion of the host is mainly distributed in the respiratory and gastrointestinal tract. Studies found that microbiota contributes to the onset and progression of many diseases, including COVID-19. Here, we firstly conclude the characterization of respiratory, gut, and oral microbial dysbiosis, including bacteria, fungi, and viruses. Then we explore the potential mechanisms of microbial involvement in COVID-19. Microbial dysbiosis could influence COVID-19 by complex interactions with SARS-CoV-2 and host immunity. Moreover, microbiota may have an impact on COVID-19 through their metabolites or modulation of ACE2 expression. Subsequently, we generalize the potential of microbiota as diagnostic markers for COVID-19 patients and its possible association with post-acute COVID-19 syndrome (PACS) and relapse after recovery. Finally, we proposed directed microbiota-targeted treatments from the perspective of gut microecology such as probiotics and prebiotics, fecal transplantation and antibiotics, and other interventions such as traditional Chinese medicine, COVID-19 vaccines, and ACE2-based treatments.

RevDate: 2022-08-29

Dong Y, Xu T, Xiao G, et al (2022)

Opportunities and challenges for synthetic biology in the therapy of inflammatory bowel disease.

Frontiers in bioengineering and biotechnology, 10:909591 pii:909591.

Inflammatory bowel disease (IBD) is a complex, chronic intestinal inflammatory disorder that primarily includes Crohn's disease (CD) and ulcerative colitis (UC). Although traditional antibiotics and immunosuppressants are known as the most effective and commonly used treatments, some limitations may be expected, such as limited efficacy in a small number of patients and gut flora disruption. A great many research studies have been done with respect to the etiology of IBD, while the composition of the gut microbiota is suggested as one of the most influential factors. Along with the development of synthetic biology and the continuing clarification of IBD etiology, broader prospects for novel approaches to IBD therapy could be obtained. This study presents an overview of the currently existing treatment options and possible therapeutic targets at the preclinical stage with respect to microbial synthesis technology in biological therapy. This study is highly correlated to the following topics: microbiota-derived metabolites, microRNAs, cell therapy, calreticulin, live biotherapeutic products (LBP), fecal microbiota transplantation (FMT), bacteriophages, engineered bacteria, and their functional secreted synthetic products for IBD medical implementation. Considering microorganisms as the main therapeutic component, as a result, the related clinical trial stability, effectiveness, and safety analysis may be the major challenges for upcoming research. This article strives to provide pharmaceutical researchers and developers with the most up-to-date information for adjuvant medicinal therapies based on synthetic biology.

RevDate: 2022-08-29

Kleber KT, Iranpur KR, Perry LM, et al (2022)

Using the canine microbiome to bridge translation of cancer immunotherapy from pre-clinical murine models to human clinical trials.

Frontiers in immunology, 13:983344.

The microbiome has clearly been established as a cutting-edge field in tumor immunology and immunotherapy. Growing evidence supports the role of the microbiome in immune surveillance, self-tolerance, and response to immune checkpoint inhibitors such as anti PD-L1 and CTLA-4 blockade (1-6). Moreover, recent studies including those using fecal microbial transplantation (FMT) have demonstrated that response to checkpoint immunotherapies may be conferred or eliminated through gut microbiome modulation (7, 8). Consequently, studies evaluating microbiota-host immune and metabolic interactions remain an area of high impact research. While observations in murine models have highlighted the importance of the microbiome in response to therapy, we lack sufficient understanding of the exact mechanisms underlying these interactions. Furthermore, mouse and human gut microbiome composition may be too dissimilar for discovery of all relevant gut microbial biomarkers. Multiple cancers in dogs, including lymphoma, high grade gliomas, melanomas and osteosarcoma (OSA) closely resemble their human analogues, particularly in regard to metastasis, disease recurrence and response to treatment. Importantly, dogs with these spontaneous cancers also have intact immune systems, suggesting that microbiome analyses in these subjects may provide high yield information, especially in the setting of novel immunotherapy regimens which are currently expanding rapidly in canine comparative oncology (9, 10). Additionally, as onco-microbiotic therapies are developed to modify gut microbiomes for maximal responsiveness, large animal models with intact immune systems will be useful for trialing interventions and monitoring adverse events. Together, pre-clinical mechanistic studies and large animal trials can help fully unlock the potential of the microbiome as a diagnostic and therapeutic target in cancer.

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RJR Experience and Expertise

Researcher

Robbins holds BS, MS, and PhD degrees in the life sciences. He served as a tenured faculty member in the Zoology and Biological Science departments at Michigan State University. He is currently exploring the intersection between genomics, microbial ecology, and biodiversity — an area that promises to transform our understanding of the biosphere.

Educator

Robbins has extensive experience in college-level education: At MSU he taught introductory biology, genetics, and population genetics. At JHU, he was an instructor for a special course on biological database design. At FHCRC, he team-taught a graduate-level course on the history of genetics. At Bellevue College he taught medical informatics.

Administrator

Robbins has been involved in science administration at both the federal and the institutional levels. At NSF he was a program officer for database activities in the life sciences, at DOE he was a program officer for information infrastructure in the human genome project. At the Fred Hutchinson Cancer Research Center, he served as a vice president for fifteen years.

Technologist

Robbins has been involved with information technology since writing his first Fortran program as a college student. At NSF he was the first program officer for database activities in the life sciences. At JHU he held an appointment in the CS department and served as director of the informatics core for the Genome Data Base. At the FHCRC he was VP for Information Technology.

Publisher

While still at Michigan State, Robbins started his first publishing venture, founding a small company that addressed the short-run publishing needs of instructors in very large undergraduate classes. For more than 20 years, Robbins has been operating The Electronic Scholarly Publishing Project, a web site dedicated to the digital publishing of critical works in science, especially classical genetics.

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Robbins is well-known for his speaking abilities and is often called upon to provide keynote or plenary addresses at international meetings. For example, in July, 2012, he gave a well-received keynote address at the Global Biodiversity Informatics Congress, sponsored by GBIF and held in Copenhagen. The slides from that talk can be seen HERE.

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Robbins is a skilled meeting facilitator. He prefers a participatory approach, with part of the meeting involving dynamic breakout groups, created by the participants in real time: (1) individuals propose breakout groups; (2) everyone signs up for one (or more) groups; (3) the groups with the most interested parties then meet, with reports from each group presented and discussed in a subsequent plenary session.

Designer

Robbins has been engaged with photography and design since the 1960s, when he worked for a professional photography laboratory. He now prefers digital photography and tools for their precision and reproducibility. He designed his first web site more than 20 years ago and he personally designed and implemented this web site. He engages in graphic design as a hobby.

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A practical handbook on fecal microbiota transplantation (FMT) for physicians, nurses, physician assistants, students, residents, and fellows, The 6 Ds of Fecal Microbiota Transplantation: A Primer from Decision to Discharge and Beyond provides a clinical framework to understand and administer this treatment. FMT has emerged as a promising treatment for C. difficile infection (CDI), and there is a major need for educational resources on the topic. Drs. Jessica Allegretti, Zain Kassam, and their expert contributors are leaders in the field and have collectively cared for thousands of patients suffering from recurrent CDI who have benefitted from FMT. This guide provides practical tools, clinical pearls, and answers to frequently asked questions. Beginning with introductory information on the microbiome and exploring the history of FMT, The 6 Ds of Fecal Microbiota Transplantation outlines a step-by-step checklist for administering FMT: Decision: Who is the right CDI patient to receive FMT? What clinical questions should you ask patients in your FMT clinical assessment?; Donor: How do you select and screen a donor for FMT?; Discussion: What are the risks, benefits, and alternatives that need to be discussed with patients?; Delivery: What is the best delivery method for FMT-colonoscopy, nasogastric tube, enema, or capsules?; Discharge and follow-up: What is the ideal post-FMT care? How should you council patients following FMT?; and Discovery: What are the most promising emerging clinical applications for FMT? What is the evidence for FMT in obesity, autism, irritable bowel syndrome, inflammatory bowel disease, antibiotic resistant bacteria, and liver disease? Arming healthcare professionals with the ability to answer questions from patients regarding FMT and the microbiome, The 6 Ds of Fecal Microbiota Transplantation provides a pragmatic guide for this exciting treatment.

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Reprints and preprints of publications, slide presentations, instructional materials, and data compilations written or prepared by Robert Robbins. Most papers deal with computational biology, genome informatics, using information technology to support biomedical research, and related matters.

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