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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 17 May 2021 at 01:33 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: 2021-05-14

Bonde A, Daly S, Kirsten J, et al (2021)

Human Gut Microbiota-associated Gastrointestinal Malignancies: A Comprehensive Review.

Radiographics : a review publication of the Radiological Society of North America, Inc [Epub ahead of print].

The human gastrointestinal tract houses trillions of microbes. The gut and various types of microorganisms, including bacteria, viruses, fungi, and archaea, form a complex ecosystem known as the gut microbiota, and the whole genome of the gut microbiota is referred to as the gut microbiome. The gut microbiota is essential for homeostasis and the overall well-being of a person and is increasingly considered an adjunct "virtual organ," with a complexity level comparable to that of the other organ systems. The gut microbiota plays an essential role in nutrition, local mucosal homeostasis, inflammation, and the mucosal immune system. An imbalanced state of the gut microbiota, known as dysbiosis, can predispose to development of various gastrointestinal malignancies through three speculated pathogenic mechanisms: (a) direct cytotoxic effects with damage to the host DNA, (b) disproportionate proinflammatory signaling inducing inflammation, and (c) activation of tumorigenic pathways or suppression of tumor-suppressing pathways. Several microorganisms, including Helicobacter pylori, Epstein-Barr virus, human papillomavirus, Mycoplasma species, Escherichia coli, and Streptococcus bovis, are associated with gastrointestinal malignancies such as esophageal adenocarcinoma, gastric adenocarcinoma, gastric mucosa-associated lymphoid tissue lymphoma, colorectal adenocarcinoma, and anal squamous cell carcinoma. Imaging plays a pivotal role in diagnosis and management of microbiota-associated gastrointestinal malignancies. Appropriate use of probiotics, fecal microbiota transplantation, and overall promotion of the healthy gut are ongoing areas of research for prevention and treatment of malignancies. Online supplemental material is available for this article.©RSNA, 2021.

RevDate: 2021-05-14

Wilson BC, Vatanen T, Jayasinghe TN, et al (2021)

Strain engraftment competition and functional augmentation in a multi-donor fecal microbiota transplantation trial for obesity.

Microbiome, 9(1):107.

BACKGROUND: Donor selection is an important factor influencing the engraftment and efficacy of fecal microbiota transplantation (FMT) for complex conditions associated with microbial dysbiosis. However, the degree, variation, and stability of strain engraftment have not yet been assessed in the context of multiple donors.

METHODS: We conducted a double-blinded randomized control trial of FMT in 87 adolescents with obesity. Participants were randomized to receive multi-donor FMT (capsules containing the fecal microbiota of four sex-matched lean donors) or placebo (saline capsules). Following a bowel cleanse, participants ingested a total of 28 capsules over two consecutive days. Capsules from individual donors and participant stool samples collected at baseline, 6, 12, and 26 weeks post-treatment were analyzed by shotgun metagenomic sequencing allowing us to track bacterial strain engraftment and its functional implications on recipients' gut microbiomes.

RESULTS: Multi-donor FMT sustainably altered the structure and the function of the gut microbiome. In what was effectively a microbiome competition experiment, we discovered that two donor microbiomes (one female, one male) dominated strain engraftment and were characterized by high microbial diversity and a high Prevotella to Bacteroides (P/B) ratio. Engrafted strains led to enterotype-level shifts in community composition and provided genes that altered the metabolic potential of the community. Despite our attempts to standardize FMT dose and origin, FMT recipients varied widely in their engraftment of donor strains.

CONCLUSION: Our study provides evidence for the existence of FMT super-donors whose microbiomes are highly effective at engrafting in the recipient gut. Dominant engrafting male and female donor microbiomes harbored diverse microbial species and genes and were characterized by a high P/B ratio. Yet, the high variability of strain engraftment among FMT recipients suggests the host environment also plays a critical role in mediating FMT receptivity.

TRIAL REGISTRATION: The Gut Bugs trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615001351505).

TRIAL PROTOCOL: The trial protocol is available at https://bmjopen.bmj.com/content/9/4/e026174 . Video Abstract.

RevDate: 2021-05-14

Kuai XY, Yao XH, Xu LJ, et al (2021)

Evaluation of fecal microbiota transplantation in Parkinson's disease patients with constipation.

Microbial cell factories, 20(1):98.

Parkinson's disease (PD) is a neurodegenerative disorder and 70-80% of PD patients suffer from gastrointestinal dysfunction such as constipation. We aimed to assess the efficacy and safety of fecal microbiota transplantation (FMT) for treating PD related to gastrointestinal dysfunction. We conducted a prospective, single- study. Eleven patients with PD received FMT. Fecal samples were collected before and after FMT and subjected to 16S ribosomal DNA (rDNA) gene sequencing. Hoehn-Yahr (H-Y) grade, Unified Parkinson's Disease Rating Scale (UPDRS) score, and the Non-Motion Symptom Questionnaire (NMSS) were used to assess improvements in motor and non-motor symptoms. PAC-QOL score and Wexner constipation score were used to assess the patient's constipation symptoms. All patients were tested by the small intestine breath hydrogen test, performed before and after FMT. Community richness (chao) and microbial structure in before-FMT PD patients were significantly different from the after-FMT. We observed an increased abundance of Blautia and Prevotella in PD patients after FMT, while the abundance of Bacteroidetes decreased dramatically. After FMT, the H-Y grade, UPDRS, and NMSS of PD patients decreased significantly. Through the lactulose H2 breath test, the intestinal bacterial overgrowth (SIBO) in PD patients returned to normal. The PAC-QOL score and Wexner constipation score in after-FMT patients decreased significantly. Our study profiles specific characteristics and microbial dysbiosis in the gut of PD patients. FMT might be a therapeutic potential for reconstructing the gut microbiota of PD patients and improving their motor and non-motor symptoms.

RevDate: 2021-05-14
CmpDate: 2021-05-14

Giles EM, J Couper (2020)

Microbiome in health and disease.

Journal of paediatrics and child health, 56(11):1735-1738.

There has been an exponential rise in research into the microbiota of the human gastrointestinal tract, particularly of the genomic content (the microbiome). The vast number of micro-organisms residing in our gut has an integral role in essential processes, including growth and development. Probiotics, live micro-organisms with putative benefits on health have become ubiquitous as treatments for many conditions, despite often limited robust clinical trial data. However, the resurgence of faecal microbial transplantation as an effective treatment modality provides further promise that manipulation of our microbiome can have clinical benefits. This review will present the recent evidence for the role of the microbiome in development and growth, and focus on the evidence for its manipulation in paediatric diseases. We will show that while there is promising data in specific diseases, there remain many unanswered questions. Only through a deeper understanding of our complex internal ecosystem will we be able to move to the next stage of targeted microbial therapy.

RevDate: 2021-05-13

Lu C, Chen J, Yi C, et al (2021)

Gut microbiota mediated the protective effects of tuna oil on collagen-induced arthritis in mice.

Food & function [Epub ahead of print].

Rheumatoid arthritis is emerging as a chronic autoimmune disease worldwide. In this study, the beneficial effects of tuna oil (TO) on collagen-induced arthritis (CIA) mice were investigated. Dietary administration of TO relieved arthritis severity and joint bone erosion, and ameliorated systemic inflammation. Furthermore, TO treatments regulated the phosphorylation of nuclear factor-kappa B (NF-κB) and Wnt1/β-catenin signaling pathways in the joint, enhanced osteoblastogenesis biomarkers and suppressed osteoclastogenesis biomarkers, and subsequently re-balanced bone remodeling. Moreover, the impaired intestinal epithelial barrier was repaired after TO treatments, along with gut microbiota modulation. By employing fecal microbiota transplantation, we clarified that the beneficial effects of TO in CIA alleviation were mediated by the modulated gut microbiota. These results indicated that gut microbiota mediated the protective effects of tuna oil on collagen-induced arthritis in mice.

RevDate: 2021-05-13

Gupta S, Mullish BH, JR Allegretti (2021)

Fecal Microbiota Transplantation: The Evolving Risk Landscape.

The American journal of gastroenterology, 116(4):647-656.

Fecal microbiota transplantation (FMT) has been recommended in clinical guidelines for the treatment of recurrent Clostridioides difficile infection (CDI). However, it is considered investigational by most regulatory agencies. As the adoption of FMT has increased from a small group of CDI experts alone to more widespread use, there has been a corresponding increase in concern regarding potential risk. FMT is largely considered a safe procedure although risks described range from mild gastrointestinal symptoms to serious infection. Currently, there is variability in how "FMT" is characterized specifically regarding testing approach, which, in turn, impacts the risk profile. This has been highlighted by the rare cases of multidrug-resistant organisms, Shiga toxin-producing Escherichia and enteropathogenic E. coli, recently reported, where these organisms were not screened. These cases have prompted additional screening mandates from the US Food and Drug Administration (FDA), which has maintained its policy of enforcement discretion for the use of FMT for CDI not responding to standard therapy. Here, we examine the evolving risk landscape of FMT.

RevDate: 2021-05-13

Sharma A (2021)

Continuing Medical Education Questions: April 2021.

The American journal of gastroenterology, 116(4):636.

Article Title: Fecal Microbiota Transplantation: The Evolving Risk Landscape.

RevDate: 2021-05-13

Wang B, Wang L, Wang H, et al (2021)

Targeting the Gut Microbiota for Remediating Obesity and Related Metabolic Disorders.

The Journal of nutrition pii:6274852 [Epub ahead of print].

The rate of obesity is rapidly increasing and has become a health and economic burden worldwide. As recent studies have revealed that the gut microbiota is closely linked to obesity, researchers have used various approaches to modulate the gut microbiota to treat the condition. Dietary composition and energy intake strongly affect the composition and function of the gut microbiota. Intestinal microbial changes alter the composition of bile acids and fatty acids and regulate bacterial lipopolysaccharide production, all of which influence energy metabolism and immunity. Evidence also suggests that remodeling the gut microbiota through intake of probiotics, prebiotics, fermented foods, and dietary plants, as well as by fecal microbiota transplantation, are feasible methods to remediate obesity.

RevDate: 2021-05-13

Liu X, Li Y, Wu K, et al (2021)

Fecal Microbiota Transplantation as Therapy for Treatment of Active Ulcerative Colitis: A Systematic Review and Meta-Analysis.

Gastroenterology research and practice, 2021:6612970.

Aim: Increasing evidence supports the role of the gut microbiota in the etiology of ulcerative colitis (UC). Fecal microbiota transplantation (FMT) is a highly effective treatment against recurrent Clostridium difficile infection; however, its efficacy in UC is still controversial. A systematic review and meta-analysis was conducted to evaluate the efficacy and safety of FMT for treatment of active UC.

Methods: We searched Cochrane, Medline, Web of Science, and Embase from inception to February 2020. Randomized controlled trials (RCTs) recruiting adults with active UC, which compared FMT with controls, were eligible. The primary outcome was combined clinical remission with endoscopic remission/response. Secondary outcomes included clinical remission, endoscopic remission, and serious adverse events. Relative risk (RR) with 95% confidence interval (CI) is reported.

Results: Five RCTs with 292 participants were eligible for inclusion. When data were pooled for all patients, FMT was associated with a higher combined clinical remission with endoscopic remission/response; the RR of combined outcome not achieving after FMT vs. control was 0.79 (95% CI 0.70-0.88). FMT delivered via lower gastrointestinal route was superior to upper gastrointestinal route with regard to combined clinical remission with endoscopic remission/response (RR = 0.79, 95% CI 0.70-0.89). FMT with pooled donor stool (RR = 0.69, 95% CI 0.56-0.85) and higher frequency of administration (RR = 0.76, 95% CI 0.62-0.93) may be more effective with regard to clinical remission. There was no statistically significant difference in serious adverse events with FMT compared with controls (RR = 0.98, 95% CI 0.93-1.03).

Conclusion: FMT shows a promising perspective with comparable safety and favorable clinical efficacy for the treatment of active UC in the short term. However, further larger, more rigorously conducted RCTs of FMT in UC are still needed in order to resolve the controversial questions.

RevDate: 2021-05-12
CmpDate: 2021-05-12

Khanna S, CS Kraft (2021)

The interplay of SARS-CoV-2 and Clostridioides difficile infection.

Future microbiology, 16:439-443.

The COVID-19 pandemic has changed the way we practice medicine and lead our lives. In addition to pulmonary symptoms; COVID-19 as a syndrome has multisystemic involvement including frequent gastrointestinal symptoms such as diarrhea. Due to microbiome alterations with COVID-19 and frequent antibiotic exposure, COVID-19 can be complicated by Clostridioides difficile infection. Co-infection with these two can be associated with a high risk of complications. Infection control measures in hospitals is enhanced due to the COVID-19 pandemic which in turn appears to reduce the incidence of hospital-acquired infections such as C. difficile infection. Another implication of COVID-19 and its potential transmissibility by stool is microbiome-based therapies. Potential stool donors should be screened COVID-19 symptoms and be tested for COVID-19.

RevDate: 2021-05-06
CmpDate: 2021-05-06

Hohmann EL (2021)

Faecal microbiota transplantation: more screening for old and new pathogens.

The Lancet. Infectious diseases, 21(5):587-589.

RevDate: 2021-05-09

Derosa L, L Zitvogel (2021)

Fecal microbiota transplantation: can it circumvent resistance to PD-1 blockade in melanoma?.

Signal transduction and targeted therapy, 6(1):178.

RevDate: 2021-05-07

Chen PJ, Nakano T, Lai CY, et al (2021)

Daily full spectrum light exposure prevents food allergy-like allergic diarrhea by modulating vitamin D3 and microbiota composition.

NPJ biofilms and microbiomes, 7(1):41.

The importance of sun exposure on human health is well recognized, and a recent trend in the avoidance of sun exposure has led to the risk of missing the beneficial effects such as vitamin D3 biogenesis. Vitamin D3 insufficiency is one of the risk factors for the development of food allergies (FAs), and vitamin D3 status controls gut homeostasis by modulating the microbiota. This study aimed to explore the impact of daily full spectrum light exposure (phototherapy) on the pathogenesis of FAs. Phototherapy ameliorated allergic diarrhea and improved FA-associated vitamin D3 insufficiency and dysbiosis. Fecal microbiota transplantation (FMT) of FA donor feces induced allergic diarrhea with OVA-specific IgE elevation in naïve mice. In contrast, FMT of naïve donor feces ameliorated allergic diarrhea in established FA mice, suggesting the involvement of the microbiota composition in FA. Phototherapy is an alternative approach for the prevention of FA-like allergic diarrhea through the modulation of vitamin D3 status and microbiota composition.

RevDate: 2021-05-10
CmpDate: 2021-05-10

Cuna A, Morowitz MJ, Ahmed I, et al (2021)

Dynamics of the preterm gut microbiome in health and disease.

American journal of physiology. Gastrointestinal and liver physiology, 320(4):G411-G419.

Advances in metagenomics have allowed a detailed study of the gut microbiome, and its role in human health and disease. Infants born prematurely possess a fragile gut microbial ecosystem that is vulnerable to perturbation. Alterations in the developing gut microbiome in preterm infants are linked to life-threatening diseases such as necrotizing enterocolitis (NEC) and late-onset sepsis; and may impact future risk of asthma, atopy, obesity, and psychosocial disease. In this mini-review, we summarize recent literature on the origins and patterns of development of the preterm gut microbiome in the perinatal period. The host-microbiome-environmental factors that portend development of dysbiotic intestinal microbial patterns associated with NEC and sepsis are reviewed. Strategies to manipulate the microbiome and mitigate dysbiosis, including the use of probiotics and prebiotics will also be discussed. Finally, we explore the challenges and future directions of gut microbiome research in preterm infants.

RevDate: 2021-05-07

Pai N, Popov J, Hill L, et al (2021)

Results of the first pilot randomized controlled trial of fecal microbiota transplant in pediatric ulcerative colitis: lessons, limitations, and future prospects.

Gastroenterology pii:S0016-5085(21)00739-3 [Epub ahead of print].

RevDate: 2021-05-07

Yadav D, S Khanna (2021)

Safety of fecal microbiota transplantation for Clostridioides difficile infection focusing on pathobionts and SARS-CoV-2.

Therapeutic advances in gastroenterology, 14:17562848211009694 pii:10.1177_17562848211009694.

Clostridioides difficile infection (CDI) is a consequence of flagrant use of antibiotics, an aging population with increasing comorbidities, and increased hospitalizations. The treatment of choice for CDI is antibiotics (vancomycin or fidaxomicin), with a possibility of recurrent CDI despite lack of additional risk factors for CDI. For the last 10 years, fecal microbiota transplantation (FMT) has emerged as a promising therapy for recurrent CDI, with success rates of over 85% compared with less than 50% with antibiotics for multiple recurrent CDI. Along with the success of FMT, several adverse and serious adverse events with FMT have been reported. These range from self-limiting abdominal pain to death due to severe sepsis. This review focuses on the safety of FMT, emphasizing the reports of transmission of pathobionts like extended-spectrum beta lactamase Escherichia coli and Shiga toxin-producing E. coli. The severe acute respiratory syndrome coronavirus-2 is a potential pathogen that could be transmitted via FMT during the COVID-19 pandemic. The challenges faced by clinicians for donor screening, clinical trials, and other aspects of FMT during the pandemic are discussed.

RevDate: 2021-05-06

Hartmann P, B Schnabl (2021)

New Developments in Microbiome in Alcohol-Associated and Nonalcoholic Fatty Liver Disease.

Seminars in liver disease, 41(1):87-102.

Alcohol-associated liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are important causes of morbidity and mortality worldwide. The intestinal microbiota is involved in the development and progression of both ALD and NAFLD. Here we describe associated changes in the intestinal microbiota, and we detail randomized clinical trials in ALD and NAFLD which evaluate treatments modulating the intestinal microbiome including fecal microbiota transplantation, probiotics, prebiotics, synbiotics, and antibiotics. Finally, we discuss precision medicine approaches targeting the intestinal microbiome to ameliorate ALD and NAFLD.

RevDate: 2021-05-06

Smitka K, Prochazkova P, Roubalova R, et al (2021)

Current Aspects of the Role of Autoantibodies Directed Against Appetite-Regulating Hormones and the Gut Microbiome in Eating Disorders.

Frontiers in endocrinology, 12:613983.

The equilibrium and reciprocal actions among appetite-stimulating (orexigenic) and appetite-suppressing (anorexigenic) signals synthesized in the gut, brain, microbiome and adipose tissue (AT), seems to play a pivotal role in the regulation of food intake and feeding behavior, anxiety, and depression. A dysregulation of mechanisms controlling the energy balance may result in eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). AN is a psychiatric disease defined by chronic self-induced extreme dietary restriction leading to an extremely low body weight and adiposity. BN is defined as out-of-control binge eating, which is compensated by self-induced vomiting, fasting, or excessive exercise. Certain gut microbiota-related compounds, like bacterial chaperone protein Escherichia coli caseinolytic protease B (ClpB) and food-derived antigens were recently described to trigger the production of autoantibodies cross-reacting with appetite-regulating hormones and neurotransmitters. Gut microbiome may be a potential manipulator for AT and energy homeostasis. Thus, the regulation of appetite, emotion, mood, and nutritional status is also under the control of neuroimmunoendocrine mechanisms by secretion of autoantibodies directed against neuropeptides, neuroactive metabolites, and peptides. In AN and BN, altered cholinergic, dopaminergic, adrenergic, and serotonergic relays may lead to abnormal AT, gut, and brain hormone secretion. The present review summarizes updated knowledge regarding the gut dysbiosis, gut-barrier permeability, short-chain fatty acids (SCFA), fecal microbial transplantation (FMT), blood-brain barrier permeability, and autoantibodies within the ghrelin and melanocortin systems in eating disorders. We expect that the new knowledge may be used for the development of a novel preventive and therapeutic approach for treatment of AN and BN.

RevDate: 2021-05-05

Panwar RB, Sequeira RP, TB Clarke (2021)

Microbiota-mediated protection against antibiotic-resistant pathogens.

Genes and immunity [Epub ahead of print].

Colonization by the microbiota provides one of our most effective barriers against infection by pathogenic microbes. The microbiota protects against infection by priming immune defenses, by metabolic exclusion of pathogens from their preferred niches, and through direct antimicrobial antagonism. Disruption of the microbiota, especially by antibiotics, is a major risk factor for bacterial pathogen colonization. Restoration of the microbiota through microbiota transplantation has been shown to be an effective way to reduce pathogen burden in the intestine but comes with a number of drawbacks, including the possibility of transferring other pathogens into the host, lack of standardization, and potential disruption to host metabolism. More refined methods to exploit the power of the microbiota would allow us to utilize its protective power without the drawbacks of fecal microbiota transplantation. To achieve this requires detailed understanding of which members of the microbiota protect against specific pathogens and the mechanistic basis for their effects. In this review, we will discuss the clinical and experimental evidence that has begun to reveal which members of the microbiota protect against some of the most troublesome antibiotic-resistant pathogens: Klebsiella pneumoniae, vancomycin-resistant enterococci, and Clostridioides difficile.

RevDate: 2021-05-05

Xu B, Qin W, Yan Y, et al (2021)

Gut microbiota contributes to the development of endometrial glands in gilts during the ovary-dependent period.

Journal of animal science and biotechnology, 12(1):57.

BACKGROUND: The hyper-prolificacy Meishan gilts achieved a superior endometrial gland development (EGD) than white crossbred gilts during the ovary-independent period (before 60 d of age). Then, the EGD continues under the management of ovary-derived steroid hormones that regulated by gut microbiota (after 60 d of age). However, whether Meishan gilts' superiority in EGD lasting to the ovary-dependent period (after 60 d of age) and the role of gut microbiota in this period both remain unclear.

METHODS: Meishan gilts and Landrace x Yorkshire (LxY) gilts were raised under the same housing and feeding conditions until sexual maturity and then we compared their EGD and gut microbiota. Meanwhile, we transplanted fecal microbiota from Meishan gilts to L×Y gilts to explore the role of gut microbiota in EGD. We sampled plasma every 3 weeks and collected the uterus, ovary, liver, and rectal feces after the sacrifice. We then determined the hormone concentrations and expressions of the EGD-related genes. We also profiled the gut microbiota using 16S rDNA sequencing and metabolites of plasma and liver tissue using untargeted metabolomics. Finally, the correlation analysis and significant test was conducted between FMT-shifted gut microbes and EGD-related indices.

RESULTS: Meishan gilts have larger endometrial gland area (P < 0.001), longer uterine horn length (P < 0.01) but lighter uterine horn weight (P < 0.05), a distinctive gut microbiota compared with L×Y gilts. Fecal microbiota transplantation (FMT) increased endometrial gland area (P < 0.01). FMT markedly shifted the metabolite profiles of both liver and plasma, and these differential metabolites enriched in steroid hormone biosynthesis pathway. FMT increased estradiol and insulin-like growth factor 1 but decreased progesterone dynamically. FMT also increased the expression of the EGD-related genes estrogen receptor 1 gene, epithelial cadherin, and forkhead box protein A2. There is a significant correlation between FMT-shifted gut microbes and EGD-related indices.

CONCLUSION: Sexually matured Meishan gilts achieved a superior EGD than LxY gilts. Meanwhile, gut microbiota contribute to the EGD potentially via regulating of steroid hormones during the ovary-dependent period.

RevDate: 2021-05-05

Han JX, Tao ZH, Qian Y, et al (2021)

ZFP90 drives the initiation of colitis-associated colorectal cancer via a microbiota-dependent strategy.

Gut microbes, 13(1):1-20.

Chronic inflammation and gut microbiota dysbiosis are risk factors for colorectal cancer. In clinical practice, patients with inflammatory bowel disease (IBD) have a greatly increased risk of developing colitis-associated colorectal cancer (CAC). However, the underlying mechanism of the initiation of CAC remains unknown. Systematic analyses using an existing genome-wide association study (GWAS) and conditional deletion of Zfp90 (encoding zinc finger protein 90 homolog) in a CAC mouse model indicated that Zfp90 is a putative oncogene in CAC development.Strikingly, depletion of the gut microbiota eliminated the tumorigenic effect of Zfp90 in the CAC mouse model. Moreover, fecal microbiota transplantation demonstrated that Zfp90 promoted CAC dependent on the gut microbiota. Analysis of 16s rDNA sequences in fecal specimens from the CAC mouse model allowed us to speculate that a Prevotella copri-defined microbiota might mediate the oncogenic role of Zfp90 in the development of CAC. Mechanistic studies revealed Zfp90 accelerated CAC development through the TLR4-PI3K-AKT-NF-κB pathway. Our findings revealed the crucial role of the Zfp90-microbiota-NF-κB axis in creating a tumor-promoting environment and suggested therapeutic targets for CAC prevention and treatment.

RevDate: 2021-05-05

Kouidhi S, Zidi O, Alhujaily M, et al (2021)

Fecal Metabolomics Reveals Distinct Profiles of Kidney Transplant Recipients and Healthy Controls.

Diagnostics (Basel, Switzerland), 11(5): pii:diagnostics11050807.

Monitoring graft recipients remains dependent on traditional biomarkers and old technologies lacking specificity, sensitivity, or accuracy. Recently, metabolomics is becoming a promising approach that may offer to kidney transplants a more effective and specific monitoring. Furthermore, emerging evidence suggested a fundamental role of gut microbiota as an important determinant of patients' metabolomes. In the current study, we enrolled forty stable renal allografts recipients compared to twenty healthy individuals. Samples were taken at different time points from patient to patient following transplantation surgery, which varied from 3 months to 22 years post-graft. All patients started the immunosuppression therapy immediately following kidney graft (Day 0). Gas chromatography-mass spectrometry (GC-MS) was employed to perform untargeted analysis of fecal metabolites. Globally, the fecal metabolic signature was significantly different between kidney transplants and the control group. Fecal metabolome was dominated by lipids (sterols and fatty acids) in the stable transplant group compared to the controls (p < 0.05). Overall, 18 metabolites were significantly altered within kidney transplant recipients. Furthermore, the most notable altered metabolic pathways in kidney transplants include ubiquinone and other terpenoid-quinone biosynthesis, tyrosine metabolism, tryptophan biosynthesis, and primary bile acid biosynthesis. Fecal metabolites could effectively distinguish stable transplant recipients from controls, supporting the potential utility of metabolomics in rapid and non-invasive diagnosis to produce relevant biomarkers and to help clinicians in monitoring kidney transplants. Further investigations are needed to clarify the physiological relevance of fecal metabolome and to assess the impact of microbiota modulation.

RevDate: 2021-05-05

Karaduta O, Dvanajscak Z, B Zybailov (2021)

Metaproteomics-An Advantageous Option in Studies of Host-Microbiota Interaction.

Microorganisms, 9(5): pii:microorganisms9050980.

Gut microbiome contributes to host health by maintaining homeostasis, increasing digestive efficiency, and facilitating the development of the immune system. Manipulating gut microbiota is being recognized as a therapeutic target to manage various chronic diseases. The therapeutic manipulation of the intestinal microbiome is achieved through diet modification, the administration of prebiotics, probiotics, or antibiotics, and more recently, fecal microbiome transplantation (FMT). In this opinion paper, we give a perspective on the current status of application of multi-omics technologies in the analysis of host-microbiota interactions. The aim of this paper was to highlight the strengths of metaproteomics, which integrates with and often relies on other approaches.

RevDate: 2021-05-05
CmpDate: 2021-05-05

Alghetaa H, Mohammed A, Zhou J, et al (2021)

Resveratrol-mediated attenuation of superantigen-driven acute respiratory distress syndrome is mediated by microbiota in the lungs and gut.

Pharmacological research, 167:105548.

Acute Respiratory Distress Syndrome (ARDS) is triggered by a variety of agents, including Staphylococcal Enterotoxin B (SEB). Interestingly, a significant proportion of patients with COVID-19, also develop ARDS. In the absence of effective treatments, ARDS results in almost 40% mortality. Previous studies from our laboratory demonstrated that resveratrol (RES), a stilbenoid, with potent anti-inflammatory properties can attenuate SEB-induced ARDS. In the current study, we investigated the role of RES-induced alterations in the gut and lung microbiota in the regulation of ARDS. Our studies revealed that SEB administration induced inflammatory cytokines, ARDS, and 100% mortality in C3H/HeJ mice. Additionally, SEB caused a significant increase in pathogenic Proteobacteria phylum and Propionibacterium acnes species in the lungs. In contrast, RES treatment attenuated SEB-mediated ARDS and mortality in mice, and significantly increased probiotic Actinobacteria phylum, Tenericutes phylum, and Lactobacillus reuteri species in both the colon and lungs. Colonic Microbiota Transplantation (CMT) from SEB-injected mice that were treated with RES as well as the transfer of L. reuteri into recipient mice inhibited the production of SEB-mediated induction of pro-inflammatory cytokines such as IFN-γ and IL-17 but increased that of anti-inflammatory IL-10. Additionally, such CMT and L. reuteri recipient mice exposed to SEB, showed a decrease in lung-infiltrating mononuclear cells, cytotoxic CD8+ T cells, NKT cells, Th1 cells, and Th17 cells, but an increase in the population of regulatory T cells (Tregs) and Th3 cells, and increase in the survival of mice from SEB-mediated ARDS. Together, the current study demonstrates that ARDS induced by SEB triggers dysbiosis in the lungs and gut and that attenuation of ARDS by RES may be mediated, at least in part, by alterations in microbiota in the lungs and the gut, especially through the induction of beneficial bacteria such as L. reuteri.

RevDate: 2021-05-05
CmpDate: 2021-05-05

Tran HQ, Bretin A, Adeshirlarijaney A, et al (2020)

"Western Diet"-Induced Adipose Inflammation Requires a Complex Gut Microbiota.

Cellular and molecular gastroenterology and hepatology, 9(2):313-333.

BACKGROUND & AIMS: Consumption of a low-fiber, high-fat, Western-style diet (WSD) induces adiposity and adipose inflammation characterized by increases in the M1:M2 macrophage ratio and proinflammatory cytokine expression, both of which contribute to WSD-induced metabolic syndrome. WSD-induced adipose inflammation might result from endoplasmic reticulum stress in lipid-overloaded adipocytes and/or dissemination of gut bacterial products, resulting in activation of innate immune signaling. Hence, we aimed to investigate the role of the gut microbiota, and its detection by innate immune signaling pathways, in WSD-induced adipose inflammation.

METHODS: Mice were fed grain-based chow or a WSD for 8 weeks, assessed metabolically, and intestinal and adipose tissue were analyzed by flow cytometry and quantitative reverse transcription polymerase chain reaction. Microbiota was ablated via antibiotics and use of gnotobiotic mice that completely lacked microbiota (germ-free mice) or had a low-complexity microbiota (altered Schaedler flora). Innate immune signaling was ablated by genetic deletion of Toll-like receptor signaling adaptor myeloid differentiation primary response 88.

RESULTS: Ablation of microbiota via antibiotic, germ-free, or altered Schaedler flora approaches did not significantly impact WSD-induced adiposity, yet dramatically reduced WSD-induced adipose inflammation as assessed by macrophage populations and cytokine expression. Microbiota ablation also prevented colonic neutrophil and CD103- dendritic cell infiltration. Such reduced indices of inflammation correlated with protection against WSD-induced dysglycemia, hypercholesterolemia, and liver dysfunction. Genetic deletion of myeloid differentiation primary response 88 also prevented WSD-induced adipose inflammation.

CONCLUSIONS: These results indicate that adipose inflammation, and some aspects of metabolic syndrome, are not purely a consequence of diet-induced adiposity per se but, rather, may require disturbance of intestine-microbiota interactions and subsequent activation of innate immunity.

RevDate: 2021-05-04
CmpDate: 2021-05-04

Karolewska-Bochenek K, Lazowska-Przeorek I, Grzesiowski P, et al (2021)

Faecal Microbiota Transfer - a new concept for treating cytomegalovirus colitis in children with ulcerative colitis.

Annals of agricultural and environmental medicine : AAEM, 28(1):56-60.

INTRODUCTION: Cytomegalovirus (CMV) infection in patients with inflammatory bowel disease (IBD) is reactivated by the use of immunosuppressive drugs. CMV infection may produce IBD flares refractory to standard therapy.

OBJECTIVE: The aim of our study was to assess the efficacy and safety of faecal microbiota transplantation (FMT) for the treatment of CMV colitis in patients with ulcerative colitis (UC) flare.

MATERIAL AND METHODS: A total of 8 children, with mild to severe UC, positive for CMV PCR in colonic biopsies, received 50-100 ml FMT by nasogastric tube on 5 consecutive days in each of 2 weeks. During the study, the subjects were treated with 5ASA and FMT. Immunosuppressant therapy was withdrawn, when CMV colitis was diagnosed by positive DNA PCR in colonic tissues. The clinical response was defined as a decrease of Paediatric UC Activity Index by ≥20 points.

RESULTS: At the 6th week of the study, negative colonic CMV DNA PCR was measured after 10 infusions in 7/8 patients. For one boy, 20 infusions were administered to assess CMV elimination from colonic biopsies. A clinical response was observed in 3/8 patients, with clinical remission in 3/8 patients. Faecal calprotectin decreased significantly in 3 patients. CRP normalized in 2 patients after 6 weeks. No serious adverse effects were observed during and after infusions.

CONCLUSIONS: FMT seems to be an effective and safe treatment option for CMV colitis in children with UC. This is the first study to demonstrate the application of FMT as a new therapeutic option for CMV colitis.

RevDate: 2021-05-03

Rubio-Del-Campo A, Gozalbo-Rovira R, Moya-Gonzálvez EM, et al (2021)

Infant gut microbiota modulation by human milk disaccharides in humanized microbiome mice.

Gut microbes, 13(1):1-20.

Human milk glycans present a unique diversity of structures that suggest different mechanisms by which they may affect the infant microbiome development. A humanized mouse model generated by infant fecal transplantation was utilized here to evaluate the impact of fucosyl-α1,3-GlcNAc (3FN), fucosyl-α1,6-GlcNAc, lacto-N-biose (LNB) and galacto-N-biose on the fecal microbiota and host-microbiota interactions. 16S rRNA amplicon sequencing showed that certain bacterial genera significantly increased (Ruminococcus and Oscillospira) or decreased (Eubacterium and Clostridium) in all disaccharide-supplemented groups. Interestingly, cluster analysis differentiates the consumption of fucosyl-oligosaccharides from galactosyl-oligosaccharides, highlighting the disappearance of Akkermansia genus in both fucosyl-oligosaccharides. An increment of the relative abundance of Coprococcus genus was only observed with 3FN. As well, LNB significantly increased the relative abundance of Bifidobacterium, whereas the absolute levels of this genus, as measured by quantitative real-time PCR, did not significantly increase. OTUs corresponding to the species Bifidobacterium longum, Bifidobacterium adolescentis and Ruminococcus gnavus were not present in the control after the 3-week intervention, but were shared among the donor and specific disaccharide groups, indicating that their survival is dependent on disaccharide supplementation. The 3FN-feeding group showed increased levels of butyrate and acetate in the colon, and decreased levels of serum HDL-cholesterol. 3FN also down-regulated the pro-inflammatory cytokine TNF-α and up-regulated the anti-inflammatory cytokines IL-10 and IL-13, and the Toll-like receptor 2 in the large intestine tissue. The present study revealed that the four disaccharides show efficacy in producing beneficial compositional shifts of the gut microbiota and in addition, the 3FN demonstrated physiological and immunomodulatory roles.

RevDate: 2021-05-03

Li Y, Xia S, Jiang X, et al (2021)

Gut Microbiota and Diarrhea: An Updated Review.

Frontiers in cellular and infection microbiology, 11:625210.

Diarrhea is a common problem to the whole world and the occurrence of diarrhea is highly associated with gut microbiota, such as bacteria, fungi, and viruses. Generally, diarrheal patients or animals are characterized by gut microbiota dysbiosis and pathogen infections may lead to diarrheal phenotypes. Of relevance, reprograming gut microbiota communities by dietary probiotics or fecal bacteria transplantation are widely introduced to treat or prevent diarrhea. In this review, we discussed the influence of the gut microbiota in the infection of diarrhea pathogens, and updated the research of reshaping the gut microbiota to prevent or treat diarrhea for the past few years. Together, gut microbiota manipulation is of great significance to the prevention and treatment of diarrhea, and further insight into the function of the gut microbiota will help to discover more anti-diarrhea probiotics.

RevDate: 2021-05-03

Chen J, Zaman A, Ramakrishna B, et al (2021)

Stool Banking for Fecal Microbiota Transplantation: Methods and Operations at a Large Stool Bank.

Frontiers in cellular and infection microbiology, 11:622949.

Objectives: Fecal microbiota transplantation (FMT) is a recommended therapy for recurrent Clostridioides difficile infection and is being investigated as a potential therapy for dozens of microbiota-mediated indications. Stool banks centralize FMT donor screening and FMT material preparation with the goal of expanding access to FMT material while simultaneously improving its safety, quality, and convenience. Although there are published consensuses on donor screening guidelines, there are few reports about the implementation of those guidelines in functioning stool banks.

Methods: To help inform consensus standards with data gathered from real-world settings and, in turn, to improve patient care, here we describe the general methodology used in 2018 by OpenBiome, a large stool bank, and its outputs in that year.

Results: In 2018, the stool bank received 7,536 stool donations from 210 donors, a daily average of 20.6 donations, and processed 4,271 of those donations into FMT preparations. The median time a screened and enrolled stool donor actively donated stool was 5.8 months. The median time between the manufacture of an FMT preparation and its shipment to a hospital or physician was 8.9 months. Half of the stool bank's partner hospitals and physicians ordered an average of 0.75 or fewer FMT preparations per month.

Conclusions: Further knowledge sharing should help inform refinements of stool banking guidelines and best practices.

RevDate: 2021-05-02

Goeser F, Sifft B, Stein-Thoeringer C, et al (2021)

Fecal microbiota transfer for refractory intestinal graft-versus-host disease - experience from two German tertiary centers.

European journal of haematology [Epub ahead of print].

RATIONALE: Steroid refractory graft-versus-host disease (sr-GvHD) represents a challenging complication after allogeneic hematopoetic cell transplantation (allo-HCT). Intestinal microbiota (IM) diversity and dysbiosis were identified as influencing factors for the development of acute GvHD. Fecal microbiota transfer (FMT) is hypothesized to restore IM dysbiosis, but there is limited knowledge about the significance of FMT in the treatment of sr-GvHD.

OBJECTIVES: We studied the effects of FMT on sr-GvHD in allo-HCT patients from two German tertiary clinical centers (n=11 patients; period: March 2017 until July 2019). To assess safety and clinical efficacy, we analyzed clinical data pre- and post-FMT (day -14 to +30 relative to FMT). Moreover, IM were analyzed in donor samples and in a subset of patients pre- and post-FMT by 16S rRNA sequencing.

RESULTS: Post-FMT, we observed no intervention-associated, systemic inflammatory responses and only minor side effects (5/11 patients: abdominal pain and transformation of peristalsis - each 3/11 and vomiting - 1/11). Stool frequencies and volumes were significantly reduced [pre- vs. post-FMT (d14): p <0.05, respectively] as well as clear attenuation regarding both grading and staging of sr-GvHD was present upon FMT. Moreover, IM analyses revealed an increase of alpha diversity as well as a compositional shifts towards the donor post-FMT.

CONCLUSIONS: In our study, we observed positive effects on sr-GVHD after FMT without the occurrence of major adverse events. Although these findings are in line with published data on benefical effects of FMT in sr-GvHD, further randomized clinical studies are urgently needed to better define the clinical validity including mode-of-action.

RevDate: 2021-05-03
CmpDate: 2021-05-03

Weinstein N, Garten B, Vainer J, et al (2020)

Managing the Microbiome: How the Gut Influences Development and Disease.

Nutrients, 13(1):.

The microbiome lies at the forefront of scientific research, as researchers work to uncover its mysterious influence on human development and disease. This paper reviews how the microbiome is studied, how researchers can improve its study, and what clinical applications microbiome research might yield. For this review, we analyzed studies concerning the role of the microbiome in disease and early development, the common methodologies by which the microbiome is researched in the lab, and modern clinical treatments for dysbiosis and their possible future applications. We found that the gut microbiome is essential for proper development of various physiological systems and that gut dysbiosis is a clear factor in the etiology of various diseases. Furthermore, we found that germ-free animal models and microbiome manipulation techniques are inadequate, reducing the efficacy of microbiome research. Nonetheless, research continues to show the significance of microbiome manipulation in the clinical treatment of disease, having shown great promise in the prevention and treatment of dysbiosis. Though the clinical applications of microbiome manipulation are currently limited, the significance of dysbiosis in the etiology of a wide array of diseases indicates the significance of this research and highlights the need for more effective research methods concerning the microbiome.

RevDate: 2021-05-03
CmpDate: 2021-05-03

Liu XJ, Wu LH, Xie WR, et al (2020)

Faecal microbiota transplantation simultaneously ameliorated patient's essential tremor and irritable bowel syndrome.

Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society, 20(5):796-798.

RevDate: 2021-04-30

Wu C, Lyu W, Hong Q, et al (2021)

Gut Microbiota Influence Lipid Metabolism of Skeletal Muscle in Pigs.

Frontiers in nutrition, 8:675445.

Gut microbiota is recognized as a strong determinant of host physiology including fat metabolism and can transfer obesity-associated phenotypes from donors to recipients. However, the relationship between gut microbiota and intramuscular fat (IMF) is still largely unknown. Obese Jinhua pigs (JP) have better meat quality that is associated with higher IMF content than lean Landrace pigs (LP). The present study was conducted to test the contribution of gut microbiota to IMF properties by transplanting fecal microbiota of adult JP and LP to antibiotics-treated mice. Similar to JP donors, the mice receiving JP's microbiota (JM) had elevated lipid and triglyceride levels and the lipoprotein lipase activity, as well as reduced mRNA level of angiopoietin-like 4 (ANGPTL4) in the gastrocnemius muscles, compared to those in mice receiving LP's microbiota (LM). High-throughput 16S rRNA sequencing confirmed that transplantation of JP and LP feces differently reconstructed the gut microbiota in both jejunum and colon of mouse recipients. In colonic samples, we observed an elevated ratio of Firmicutes to Bacteroidetes and increased abundance of genus Romboutsia in JM, which were positively correlated with obesity. Furthermore, the abundance of Akkermansia decreased in JM, which is positively correlated with lean. Colonic concentrations of acetate (P = 0.047) and butyrate (P = 0.014) were significantly lower in JM than in LM, and consistently, the terminal genes for butyrate synthesis, butyryl CoA: acetate CoA transferase were less abundant in colonic microbiota of JM. Taken together, these gut microbiota of obese JP intrinsically promotes IMF accumulation and can transfer the properties to mouse recipients. Manipulation of intestinal microbiota will, therefore, have the potential to improve the meat quality and flavor of pigs and even to ameliorate the metabolic syndrome in human.

RevDate: 2021-04-30

Li W, Deng X, T Chen (2021)

Exploring the Modulatory Effects of Gut Microbiota in Anti-Cancer Therapy.

Frontiers in oncology, 11:644454.

In the recent decade, gut microbiota has received growing interest due to its role in human health and disease. On the one hand, by utilizing the signaling pathways of the host and interacting with the immune system, the gut microbiota is able to maintain the homeostasis in human body. This important role is mainly modulated by the composition of microbiota, as a normal microbiota composition is responsible for maintaining the homeostasis of human body, while an altered microbiota profile could contribute to several pathogenic conditions and may further lead to oncogenesis and tumor progression. Moreover, recent insights have especially focused on the important role of gut microbiota in current anticancer therapies, including chemotherapy, radiotherapy, immunotherapy and surgery. Research findings have indicated a bidirectional interplay between gut microbiota and these therapeutic methods, in which the implementation of different therapeutic methods could lead to different alterations in gut microbiota, and the presence of gut microbiota could in turn contribute to different therapeutic responses. As a result, manipulating the gut microbiota to reduce the therapy-induced toxicity may provide an adjuvant therapy to achieve a better therapeutic outcome. Given the complex role of gut microbiota in cancer treatment, this review summarizes the interactions between gut microbiota and anticancer therapies, and demonstrates the current strategies for reshaping gut microbiota community, aiming to provide possibilities for finding an alternative approach to lower the damage and improve the efficacy of cancer therapy.

RevDate: 2021-04-30

Scibelli N, Singh P, K Raynor (2021)

Intestinal Dysbiosis Disguised as a Rectal Fistula Treated With Autologous Fecal Microbiota Transplantation.

Cureus, 13(3):e14115.

Fecal microbiota transplantation (FMT) has been efficacious in the treatment of intestinal dysbiosis, derangement of the native intestinal microflora, and the indications for autologous FMT are growing. A 69-year-old Caucasian man with a past medical history of paraplegia secondary to motor vehicle accident and sigmoid-end colostomy presented to his gastroenterologist with the complaint of rectal discharge. A complicated medical course pre-dated his presentation and included multiple decubitus ulcers requiring debridement and several courses of broad-spectrum antibiotics. The rectal discharge was initially presumed to be from a fistula leading to one of his ulcers; however, workup with anoscopy, flexible sigmoidoscopy, and magnetic resonance imaging of the pelvis showed no visible perirectal abscess or connection to the sigmoid colon through a fistula. Intestinal dysbiosis was an alternative theory considered to be the cause of his copious rectal discharge due to his several courses of broad-spectrum antibiotics and prolonged inactivity of his gut. This prompted a trial treatment plan utilizing autologous FMT, with the patient administering enemas containing his own stool to the distal limb of his bowel. As a result of this treatment, the patient's chief complaint completely resolved within days of initiating treatment, although symptoms did eventually return. We would like to propose that further randomized studies should be done to investigate autologous FMT as a treatment for patients suffering from intestinal dysbiosis following sigmoid-end colostomy.

RevDate: 2021-04-30

Zhang L, Ma X, Liu P, et al (2021)

Treatment and mechanism of fecal microbiota transplantation in mice with experimentally induced ulcerative colitis.

Experimental biology and medicine (Maywood, N.J.) [Epub ahead of print].

Restoring intestinal microbiota dysbiosis with fecal microbiota transplantation is considered as a promising treatment for ulcerative colitis. However, the mechanisms underlying its relieving effects remain unclear. Ulcerative colitis pathogenesis is associated with the involvement of immune cells and inflammatory cytokines. Here, we aimed to investigate the effect of fecal microbiota transplantation on T cell cytokines in a dextran sulfate sodium-induced ulcerative colitis mouse model. Five-aminosalicylic acid (5-ASA) was used as the positive control. Male C57BL/6 mice were randomly assigned to control, model (UC), UC + FMT, and UC + 5-ASA groups. Each group consisted of five mice. The establishment of the mouse model was verified by fecal occult-blood screening and hematoxylin-eosin staining. Results showed that fecal microbiota transplantation reduced colonic inflammation, significantly decreased T helper (Th)1 and Th17 cells, interferon-gamma, interleukin-2 and interleukin-17, as well as significantly increased Th2 and regulatory T (Treg) cells, interleukin-4, interleukin-10, and transforming growth factor-beta, and improved routine blood count. Furthermore, 16S rRNA gene-sequencing analysis showed a significant increase in the relative abundance of genus Akkermansia and a significant decrease in the relative abundance of genus Helicobacter in the ulcerative colitis group. Fecal microbiota transplantation restored the profile of the intestinal microbiota to that of the control group. These findings demonstrated the capability of fecal microbiota transplantation in controlling experimentally induced ulcerative colitis by improving Th1/Th2 and Th17/Treg imbalance through the regulation of intestinal microbiota.

RevDate: 2021-04-30

Polak K, Bergler-Czop B, Szczepanek M, et al (2021)

Psoriasis and Gut Microbiome-Current State of Art.

International journal of molecular sciences, 22(9): pii:ijms22094529.

Psoriasis is a chronic, immune-mediated inflammatory disease that affects around 125 million people worldwide. Several studies concerning the gut microbiota composition and its role in disease pathogenesis recently demonstrated significant alterations among psoriatic patients. Certain parameters such as Firmicutes/Bacteroidetes ratio or Psoriasis Microbiome Index were developed in order to distinguish between psoriatic and healthy individuals. The "leaky gut syndrome" and bacterial translocation is considered by some authors as a triggering factor for the onset of the disease, as it promotes chronic systemic inflammation. The alterations were also found to resemble those in inflammatory bowel diseases, obesity and certain cardiovascular diseases. Microbiota dysbiosis, depletion in SCFAs production, increased amount of produced TMAO, dysregulation of the pathways affecting the balance between lymphocytes populations seem to be the most significant findings concerning gut physiology in psoriatic patients. The gut microbiota may serve as a potential response-to-treatment biomarker in certain cases of biological treatment. Oral probiotics administration as well as fecal microbial transplantation were most reported in bringing health benefits to psoriatic patients. However, the issue of psoriatic bacterial gut composition, its role and healing potential needs further investigation. Here we reviewed the literature on the current state of the relationship between psoriasis and gut microbiome.

RevDate: 2021-04-30

Nomura K, Ishikawa D, Okahara K, et al (2021)

Bacteroidetes Species Are Correlated with Disease Activity in Ulcerative Colitis.

Journal of clinical medicine, 10(8): pii:jcm10081749.

Fecal microbiota transplantation following triple-antibiotic therapy (amoxicillin/fosfomycin/metronidazole) improves dysbiosis caused by reduced Bacteroidetes diversity in patients with ulcerative colitis (UC). We investigated the correlation between Bacteroidetes species abundance and UC activity. Fecal samples from 34 healthy controls and 52 patients with active UC (Lichtiger's clinical activity index ≥5 or Mayo endoscopic subscore ≥1) were subjected to next-generation sequencing with HSP60 as a target in bacterial metagenome analysis. A multiplex gene expression assay using colonoscopy-harvested mucosal tissues determined the involvement of Bacteroidetes species in the mucosal immune response. In patients with UC, six Bacteroides species exhibited significantly lower relative abundance, and twelve Bacteroidetes species were found significantly correlated with at least one metric of disease activity. The abundance of five Bacteroidetes species (Alistipes putredinis, Bacteroides stercoris, Bacteroides uniformis, Bacteroides rodentium, and Parabacteroides merdae) was correlated with three metrics, and their cumulative relative abundance was strongly correlated with the sum of Mayo endoscopic subscore (R = -0.71, p = 2 × 10-9). Five genes (TARP, C10ORF54, ITGAE, TNFSF9, and LCN2) associated with UC pathogenesis were expressed by the 12 key species. The loss of key species may exacerbate UC activity, serving as potential biomarkers.

RevDate: 2021-04-30
CmpDate: 2021-04-30

Raftery AL, Tsantikos E, Harris NL, et al (2020)

Links Between Inflammatory Bowel Disease and Chronic Obstructive Pulmonary Disease.

Frontiers in immunology, 11:2144.

Inflammatory bowel disease (IBD) and chronic obstructive pulmonary disease (COPD) are chronic inflammatory diseases of the gastrointestinal and respiratory tracts, respectively. These mucosal tissues bear commonalities in embryology, structure and physiology. Inherent similarities in immune responses at the two sites, as well as overlapping environmental risk factors, help to explain the increase in prevalence of IBD amongst COPD patients. Over the past decade, a tremendous amount of research has been conducted to define the microbiological makeup of the intestine, known as the intestinal microbiota, and determine its contribution to health and disease. Intestinal microbial dysbiosis is now known to be associated with IBD where it impacts upon intestinal epithelial barrier integrity and leads to augmented immune responses and the perpetuation of chronic inflammation. While much less is known about the lung microbiota, like the intestine, it has its own distinct, diverse microflora, with dysbiosis being reported in respiratory disease settings such as COPD. Recent research has begun to delineate the interaction or crosstalk between the lung and the intestine and how this may influence, or be influenced by, the microbiota. It is now known that microbial products and metabolites can be transferred from the intestine to the lung via the bloodstream, providing a mechanism for communication. While recent studies indicate that intestinal microbiota can influence respiratory health, intestinal dysbiosis in COPD has not yet been described although it is anticipated since factors that lead to dysbiosis are similarly associated with COPD. This review will focus on the gut-lung axis in the context of IBD and COPD, highlighting the role of environmental and genetic factors and the impact of microbial dysbiosis on chronic inflammation in the intestinal tract and lung.

RevDate: 2021-04-29

Xu HM, Huang HL, Xu J, et al (2021)

Cross-Talk Between Butyric Acid and Gut Microbiota in Ulcerative Colitis Following Fecal Microbiota Transplantation.

Frontiers in microbiology, 12:658292.

Fecal microbiota transplantation (FMT) can inhibit the progression of ulcerative colitis (UC). However, how FMT modulates the gut microbiota and which biomarker is valuable for evaluating the efficacy of FMT have not been clarified. This study aimed to determine the changes in the gut microbiota and their relationship with butyric acid following FMT for UC. Fecal microbiota (FM) was isolated from healthy individuals or mice and transplanted into 12 UC patients or colitis mice induced by dextran sulfate sodium (DSS). Their clinical colitis severities were monitored. Their gut microbiota were analyzed by 16S sequencing and bioinformatics. The levels of fecal short-chain fatty acids (SCFAs) from five UC patients with recurrent symptoms after FMT and individual mice were quantified by liquid chromatography-mass spectrometry (LC-MS). The impact of butyric acid on the abundance and diversity of the gut microbiota was tested in vitro. The effect of the combination of butyric acid-producing bacterium and FMT on the clinical responses of 45 UC patients was retrospectively analyzed. Compared with that in the controls, the FMT significantly increased the abundance of butyric acid-producing bacteria and fecal butyric acid levels in UC patients. The FMT significantly increased the α-diversity, changed gut microbial structure, and elevated fecal butyric acid levels in colitis mice. Anaerobic culture with butyrate significantly increased the α-diversity of the gut microbiota from colitis mice and changed their structure. FMT combination with Clostridium butyricum-containing probiotics significantly prolonged the UC remission in the clinic. Therefore, fecal butyric acid level may be a biomarker for evaluating the efficacy of FMT for UC, and addition of butyrate-producing bacteria may prolong the therapeutic effect of FMT on UC by changing the gut microbiota.

RevDate: 2021-04-29

Schmidt C, Grunert PC, A Stallmach (2021)

An Update for Pharmacologists on New Treatment Options for Inflammatory Bowel Disease: The Clinicians' Perspective.

Frontiers in pharmacology, 12:655054 pii:655054.

The introduction of anti-tumor necrosis factor antibodies resulted in a considerable expansion of the options available for the treatment of inflammatory bowel disease. Unfortunately, approximately one third of treated patients do not respond to these modalities, and drug efficacy may be lost over time. These drugs are also associated with contraindications, adverse events, and intolerance. As such, there is an ongoing need for new therapeutic strategies. Despite several recent advances, including antibodies against pro-inflammatory cytokines and cell adhesion molecules, Janus kinase inhibitors, and modulators of sphingosine-1-phosphate receptors, not all problems associated with IBD have been solved. In this manuscript, we review the current state of development of several new treatment options. Ongoing evaluation will require specific proof of efficacy as well as direct comparisons with established treatments. Results from head-to-head comparisons are needed to provide clinicians with critical information on how to formulate effective therapeutic approaches for each patient.

RevDate: 2021-04-29

Su F, Luo Y, Yu J, et al (2021)

Tandem fecal microbiota transplantation cycles in an allogeneic hematopoietic stem cell transplant recipient targeting carbapenem-resistant Enterobacteriaceae colonization: a case report and literature review.

European journal of medical research, 26(1):37.

BACKGROUND: Due to limited antibiotic options, carbapenem-resistant Enterobacteriaceae (CRE) infections are associated with high non-relapse mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Also, intestinal CRE colonization is a risk factor for subsequent CRE infection. Several clinical studies have reported successful fecal microbiota transplantation (FMT) for the gut decontamination of a variety of multidrug-resistant bacteria (MDRB), even in immunosuppressed patients. Similarly, other studies have also indicated that multiple FMTs may increase or lead to successful therapeutic outcomes.

CASE PRESENTATION: We report CRE colonization in an allo-HSCT patient with recurrent CRE infections, and its successful eradication using tandem FMT cycles at 488 days after allo-HSCT. We also performed a comprehensive microbiota analysis. No acute or delayed adverse events (AEs) were observed. The patient remained clinically stable with CRE-negative stool culture at 26-month follow-up. Our analyses also showed some gut microbiota reconstruction. We also reviewed the current literature on decolonization strategies for CRE.

CONCLUSIONS: CRE colonization led to a high no-relapse mortality after allo-HSCT; however, well-established decolonization strategies are currently lacking. The successful decolonization of this patient suggests that multiple FMT cycles may be potential options for CRE decolonization.

RevDate: 2021-04-29
CmpDate: 2021-04-29

Kousgaard SJ, Nielsen HL, Kirk KF, et al (2020)

Faecal microbiota transplantation to chronic pouchitis improves quality of life: a pilot study.

International journal of colorectal disease, 35(11):2135-2136.

RevDate: 2021-04-28

Danne C, Rolhion N, H Sokol (2021)

Recipient factors in faecal microbiota transplantation: one stool does not fit all.

Nature reviews. Gastroenterology & hepatology [Epub ahead of print].

Faecal microbiota transplantation (FMT) is a promising therapy for chronic diseases associated with gut microbiota alterations. FMT cures 90% of recurrent Clostridioides difficile infections. However, in complex diseases, such as inflammatory bowel disease, irritable bowel syndrome and metabolic syndrome, its efficacy remains variable. It is accepted that donor selection and sample administration are key determinants of FMT success, yet little is known about the recipient factors that affect it. In this Perspective, we discuss the effects of recipient parameters, such as genetics, immunity, microbiota and lifestyle, on donor microbiota engraftment and clinical efficacy. Emerging evidence supports the possibility that controlling inflammation in the recipient intestine might facilitate engraftment by reducing host immune system pressure on the newly transferred microbiota. Deciphering FMT engraftment rules and developing novel therapeutic strategies are priorities to alleviate the burden of chronic diseases associated with an altered gut microbiota such as inflammatory bowel disease.

RevDate: 2021-04-28
CmpDate: 2021-04-28

Shen H, Guan Q, Zhang X, et al (2020)

New mechanism of neuroinflammation in Alzheimer's disease: The activation of NLRP3 inflammasome mediated by gut microbiota.

Progress in neuro-psychopharmacology & biological psychiatry, 100:109884.

Alzheimer's disease (AD) is a central degenerative disease characterized by cognitive impairment. Polymerization of β-amyloid has been reported to cause the entanglement of nerve cells, leading to the progressive loss of nerve cells. Accumulative studies have confirmed the important roles of neuroinflammation in the development of AD. In this study, the gut microbiota from AD patients were transplanted into APP/PS1 double transgenic mice. As a result, the expression of NLRP3 was increased in the intestinal tract of mice, and the expression levels of inflammatory factors in peripheral blood were also increased. Consistently, the cognitive impairment was more severe in mice receiving gut microbiota from AD patients than those did not, with activation of microglia in the central hippocampus of mice, and increased expression of neuroinflammatory factors. In APP/PS1 mice transplanted with gut microbiota from AD patients, transplantation of healthy human gut microbiota or oral administration of minocycline was further used to improve the composition of gut microbiota. Consequently, the intestinal expression of NLRP3 was down-regulated, the cognitive ability of mice was improved, the activation of microglia in central hippocampus was suppressed and the expression of neuroinflammatory factors was also down-regulated. After transplantation of gut microbiota from AD patients in C57BL/6 mice, the intestinal expression of NLRP3 was up-regulated. Although the cognitive ability of mice was not significantly changed, the microglia in the hippocampus of mice were still activated and the expression of inflammatory factors was up-regulated. In this study, we found that gut microbiota in AD patients could induce the activation of NLRP3 inflammasome in the intestinal tract of mice, subsequently causing the release of inflammatory factors. The absorption and circulation of inflammatory factors through the intestinal tract could further aggravate the inflammation in the nervous tissues and the activation of microglia. Therefore, improving the composition of gut microbiota in AD patients can further attenuate neuroinflammation, which is considered as a novel idea for AD treatment.

RevDate: 2021-04-27
CmpDate: 2021-04-27

Xiang L, Ding X, Li Q, et al (2020)

Efficacy of faecal microbiota transplantation in Crohn's disease: a new target treatment?.

Microbial biotechnology, 13(3):760-769.

The efficacy of faecal microbiota transplantation (FMT) in Crohn's disease (CD) remains unclear due to lack of data. This study aimed to assess the value of FMT in treating CD-related clinical targets. The use of FMT for CD as a registered trial (NCT01793831) was performed between October 2012 and December 2017. Seven therapeutic targets included abdominal pain, diarrhoea, hematochezia, fever, steroid-dependence, enterocutaneous fistula and active perianal fistula. Each target was recorded as 1 (yes) or 0 (no) during the long-term follow-up for each patient. The primary outcome was the rate of improvement in each therapeutic target. Overall, 174 patients completed the follow-up. The median follow-up duration was 43 (interquartile range, 28-59) months. The median score of the total targets was 2 (range, 1-4) before FMT, and it decreased significantly at 1, 3, 6, 12, 24 and 36 months after FMT (P < 0.001 respectively). At 1 month after FMT, 72.7% (101/139), 61.6% (90/146), 76% (19/25) and 70.6% (12/17) of patients achieved improvement in abdominal pain, diarrhoea, hematochezia and fever respectively. Furthermore, 50% (10/20) of steroid-dependent patients achieved steroid-free remission after FMT. The present findings indicate that it is important to understand the efficacy of FMT in CD as a targeted therapy, especially for abdominal pain, hematochezia, fever and diarrhoea.

RevDate: 2021-04-26

Huda MN, Kim M, BJ Bennett (2021)

Modulating the Microbiota as a Therapeutic Intervention for Type 2 Diabetes.

Frontiers in endocrinology, 12:632335.

Mounting evidence suggested that the gut microbiota has a significant role in the metabolism and disease status of the host. In particular, Type 2 Diabetes (T2D), which has a complex etiology that includes obesity and chronic low-grade inflammation, is modulated by the gut microbiota and microbial metabolites. Current literature supports that unbalanced gut microbial composition (dysbiosis) is a risk factor for T2D. In this review, we critically summarize the recent findings regarding the role of gut microbiota in T2D. Beyond these associative studies, we focus on the causal relationship between microbiota and T2D established using fecal microbiota transplantation (FMT) or probiotic supplementation, and the potential underlying mechanisms such as byproducts of microbial metabolism. These microbial metabolites are small molecules that establish communication between microbiota and host cells. We critically summarize the associations between T2D and microbial metabolites such as short-chain fatty acids (SCFAs) and trimethylamine N-Oxide (TMAO). Additionally, we comment on how host genetic architecture and the epigenome influence the microbial composition and thus how the gut microbiota may explain part of the missing heritability of T2D found by GWAS analysis. We also discuss future directions in this field and how approaches such as FMT, prebiotics, and probiotics supplementation are being considered as potential therapeutics for T2D.

RevDate: 2021-04-26

Sugita K, Shima A, Takahashi K, et al (2021)

Successful outcome after a single endoscopic fecal microbiota transplantation in a Shiba dog with non-responsive enteropathy during the treatment with chlorambucil.

The Journal of veterinary medical science [Epub ahead of print].

A 7-year 6-month-old, castrated male Shiba dog presented with a 1-month history of lethargy, anorexia, vomiting, and frequent watery diarrhea. Weight loss, hypoalbuminemia, anemia, and leukocytosis were detected at the first visit. The dog was diagnosed with non-responsive enteropathy (NRE) based on clinical and histopathological examinations. Since the dog did not respond to the immunosuppressive drugs, fecal microbiota transplantation (FMT) was performed during the treatment with chlorambucil. A single endoscopic FMT into the cecum and colon drastically recovered clinical signs and clinicopathological abnormalities and corrected dysbiosis in the dog. No recurrence or adverse events were observed. The present case report suggests that FMT, possibly together with chlorambucil, might be a treatment option for NRE in Shiba dogs that have poorer prognosis compared with other dog breeds.

RevDate: 2021-04-26
CmpDate: 2021-04-26

Yu F, Jiang R, Han W, et al (2020)

Gut microbiota transplantation from db/db mice induces diabetes-like phenotypes and alterations in Hippo signaling in pseudo germ-free mice.

Aging, 12(23):24156-24167.

Type 2 diabetes mellitus (T2DM) is an age-related metabolic disease that is of increasing concern. Gut microbiota might have a critical role in the pathogenesis of T2DM. Additionally, Hippo signaling has been associated strongly with the progression of T2DM and the aging process. We adopted db/db male mice as a T2DM model, and the gut microbiota of db/db and m/m mice were transplanted successfully into pseudo germ-free mice. Furthermore, Hippo signaling, including mammalian sterile 20-like protein kinases 1 (MST1), large tumor suppressors 1 (LATS1), Yes-associated protein (YAP), and phosphorylation of YAP (p-YAP) in peripheral tissues were significantly altered and highly correlated with blood glucose in db/db mice. Interestingly, the host after gut microbiota transplantation from db/db mice showed decreased MST1 and LATS1 levels, and p-YAP/YAP ratio in the heart, liver, and kidney compared to those from m/m mice. Negative correlations between fasting blood glucose and Hippo signaling levels in selected peripheral tissues also were identified. These findings suggest that alterations in Hippo signaling in selected peripheral tissues may contribute to the development of T2DM, and that therapeutic interventions improving Hippo signaling by gut microbiota transplantation might be beneficial for the treatment of T2DM and other age-related metabolic diseases.

RevDate: 2021-04-23

Kong C, Yan X, Liu Y, et al (2021)

Ketogenic diet alleviates colitis by reduction of colonic group 3 innate lymphoid cells through altering gut microbiome.

Signal transduction and targeted therapy, 6(1):154.

Accumulating evidence suggests that ketogenic diets (KDs) mediate the rise of circulating ketone bodies and exert a potential anti-inflammatory effect; however, the consequences of this unique diet on colitis remain unknown. We performed a series of systematic studies using a dextran sulfate sodium (DSS) animal model of inflammatory colitis. Animals were fed with a KD, low-carbohydrate diet (LCD), or normal diet (ND). Germ-free mice were utilized in validation experiments. Colon tissues were analyzed by transcriptome sequencing, RT2 profiler PCR array, histopathology, and immunofluorescence. Serum samples were analyzed by metabolic assay kit. Fecal samples were analyzed by 16S rRNA gene sequencing, liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. We observed that KD alleviated colitis by altering the gut microbiota and metabolites in a manner distinct from LCD. Quantitative diet experiments confirmed the unique impact of KD relative to LCD with a reproducible increase in Akkermansia, whereas the opposite was observed for Escherichia/Shigella. After colitis induction, the KD protected intestinal barrier function, and reduced the production of RORγt+CD3- group 3 innate lymphoid cells (ILC3s) and related inflammatory cytokines (IL-17α, IL-18, IL-22, Ccl4). Finally, fecal microbiota transplantation into germ-free mice revealed that the KD- mediated colitis inhibition and ILC3 regulation were dependent on the modification of gut microbiota. Taken together, our study presents a global view of microbiome-metabolomics changes that occur during KD colitis treatment, and identifies the regulation of gut microbiome and ILC3s as novel targets involving in IBD dietary therapy.

RevDate: 2021-04-22

Bayoumy AB, Mulder CJJ, Mol JJ, et al (2021)

Gut fermentation syndrome: A systematic review of case reports.

United European gastroenterology journal [Epub ahead of print].

BACKGROUND: The gut fermentation syndrome (GFS), also known as the endogenous alcohol fermentation syndrome or auto brewery syndrome, is a rare and underdiagnosed medical condition where consumed carbohydrates are converted to alcohol by the microbiota in the gastrointestinal or urinary tract. The symptoms of GFS can have severe impact on patients' wellbeing and can have social and legal consequences. Unfortunately, not much is reported about GFS. The aim of this systematic review was to assess the evidence for GFS, causal micro-organisms, diagnostics, and possible treatments.

METHODS: A protocol was developed prior to initiation of the systematic review (PROSPERO 207182). We performed a literature search for clinical studies on 1 September 2020 using PubMed and Embase. We included all clinical studies, including case reports that described the GFS.

RESULTS: In total, 17 case reports were included, consisting of 20 patients diagnosed with GFS. The species that caused the GFS included Klebsiella pneumoniae, Candida albicans, C. glabrata, Saccharomyces cerevisiae, C. intermedia, C. parapsilosis, and C. kefyr.

CONCLUSIONS: GFS is a rare but underdiagnosed disease in daily practice. The disease is mostly reported by Saccharomyces and Candida genera, and some cases were previously treated with antibiotics. Studies in Nonalcoholic Fatty Liver disease suggest a bacterial origin of endogenous alcohol-production, which might also be causal micro-organisms in GFS. Current treatments for GFS include antibiotics, antifungal medication, low carbohydrate diet, and probiotics. There might be a potential role of fecal microbiota transplant in the treatment of GFS.

RevDate: 2021-04-22

de Clercq NC, van den Ende T, Prodan A, et al (2021)

Fecal Microbiota Transplantation from Overweight or Obese Donors in Cachectic Patients with Advanced Gastroesophageal Cancer: A Randomized, Double-blind, Placebo-controlled, Phase II Study.

Clinical cancer research : an official journal of the American Association for Cancer Research pii:1078-0432.CCR-20-4918 [Epub ahead of print].

PURPOSE: Cachexia is a multifactorial syndrome, associated with poor survival in cancer patients and is influenced by the gut microbiota. We investigated the effects of fecal microbiota transplantation (FMT) on cachexia and treatment response in patients with advanced gastroesophageal cancer (GEC).

EXPERIMENTAL DESIGN: In a double-blind randomized placebo-controlled trial performed in the Amsterdam University Medical Center, we assigned 24 cachectic patients with metastatic HER2-negative GEC to either allogenic FMT (healthy obese donor) or autologous FMT, prior to palliative chemotherapy (capecitabine and oxaliplatin). Primary objective was to assess the effect of allogenic FMT on satiety. Secondary outcomes were other features of cachexia, along with disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and toxicity. Finally, exploratory analyses were performed on the effect of FMT on gut microbiota composition (metagenomic sequencing) and metabolites (untargeted metabolomics).

RESULTS: Allogenic FMT did not improve any of the cachexia outcomes. Patients in the allogenic group (n=12) had a higher DCR at 12 weeks (p=0.035) compared to the autologous group (n=12), longer median OS of 365 vs 227 days, HR=0.38 (0.14-1.05; p=0.057) and PFS of 204 vs. 93 days, HR=0.50 (0.21-1.20; p=0.092). Patients in the allogenic group showed a significant shift in fecal microbiota composition after FMT (p=0.010) indicating proper engraftment of the donor microbiota.

CONCLUSIONS: FMT from a healthy obese donor prior to first-line chemotherapy did not affect cachexia, but may have improved response and survival in patients with metastatic GEC. These results provide a rational for larger FMT trials.

RevDate: 2021-04-22

Rinott E, Youngster I, Meir AY, et al (2021)

Autologous fecal microbiota transplantation can retain the metabolic achievements of dietary interventions.

European journal of internal medicine pii:S0953-6205(21)00110-2 [Epub ahead of print].

BACKGROUND: We recently reported that autologous fecal microbiota transplantation (aFMT), derived from the time of maximal weight-loss and administrated in the regain-phase, might preserve weight loss and glycemic control in moderately obese subjects, and is associated with specific microbiome signatures. Here, we sought to explore the global effect of aFMT on adipokines, inflammatory markers and blood cholesterol and on the overall gut microbiome preservation.

METHODS: In the DIRECT-PLUS weight-loss trial, abdominally obese participants were randomized to three distinct weight-loss diets. Following the expected weight loss phase (0-6 m), 90 participants were randomized to receive their personal frozen fecal microbiota or placebo oral capsules (ten 1 g-capsules over ten sessions-total=100 g) during the expected weight regain phase (8-14 m).

RESULTS: Of the 90 participants (age=52 yr; 0-6 m weight loss=-8.3 kg), 95.6% ingested at least 80/100 oral aFMT/placebo capsules over 6 months. Overall, the gut microbiome community structure was associated with plasma levels of leptin, cholesterol and interleukin-6 at baseline and after 6 m, whereas 6 m (weight loss phase) changes in specific microbiome species associated with the dynamic of leptin and inflammatory biomarkers. Following the 8-14 m aFMT administration phase, aFMT maintained decreased levels of leptin (ΔaFMT=-3.54 ng/mL vs. Δplacebo=-0.82 ng/mL;P = 0.04), C-reactive-protein (ΔaFMT=-1.45 mg/L vs. Δplacebo=-0.66 mg/L;P = 0.009), Interleukin-6 (ΔaFMT=-0.03pg/mL vs. Δplacebo=1.11pg/mL;P = 0.03) and total cholesterol (ΔaFMT=2.2 mg/dl vs. Δplacebo=13.1 mg/dl;P = 0.04) achieved in the weight loss phase. Overall, aFMT induced a significant preservatory effect on personal gut microbiome global composition (P = 0.03;Jensen-Shannon distance), as compared to placebo.

CONCLUSIONS: aFMT treatment in the regain phase might retain weight-loss induced metabolic benefits. These findings may suggest a novel aFMT treatment approach for personal metabolic attainment preservation.

RevDate: 2021-04-22

Van Lier YF, Van den Brink MRM, Hazenberg MD, et al (2021)

The post-hematopoietic cell transplantation microbiome: relationships with transplant outcome and potential therapeutic targets.

Haematologica [Epub ahead of print].

Microbiota injury occurs in many patients undergoing allogeneic hematopoietic cell transplantation, likely as a consequence of conditioning regimens involving chemo- and radiotherapy, the widespread use of both prophylactic and therapeutic antibiotics, and profound dietary changes during the peri-transplant period. Peri-transplant dysbiosis is characterized by a decrease in bacterial diversity, loss of commensal bacteria and single-taxon domination (e.g., with Enterococcal strains). Clinically, deviation of the post-transplant microbiota from a normal, high-diversity, healthy state has been associated with increased risk of bacteremia, development of graft-versus-host disease and decreases in overall survival. A number of recent clinical trials have attempted to target the microbiota in allogeneic hematopoietic cell transplantation patients via dietary interventions, selection of therapeutic antibiotics, administration of pre- or pro-biotics, or by performing fecal microbiota transplantation. These strategies have yielded promising results but the mechanisms by which these interventions influence transplant-related complications remain largely unknown. In this review we summarize the current approaches to targeting the microbiota, discuss potential underlying mechanisms and highlight the key outstanding areas that require further investigation in order to advance microbiota- targeting therapies.

RevDate: 2021-04-21

Metta V, Leta V, Mrudula KR, et al (2021)

Gastrointestinal dysfunction in Parkinson's disease: molecular pathology and implications of gut microbiome, probiotics, and fecal microbiota transplantation.

Journal of neurology [Epub ahead of print].

Gastrointestinal symptoms and gut dysbiosis may occur before the onset of motor symptoms in Parkinson's disease (PD). Prediagnostic and prodromal features, such as constipation and α-synuclein pathology, can be detected several years before the clinical diagnosis of PD and have the potential to develop as early PD biomarkers. Environmental toxins and gut dysbiosis may trigger oxidative stress and mucosal inflammation, and initiate α-synuclein accumulation in the enteric nervous system, early in PD. Chronic gut inflammation can lead to a leaky gut and systemic inflammation, neuro inflammation, and neuro degeneration via gut-vagus-brain signaling or through blood-brain barrier permeability. Concepts regarding the gut-brain signaling in PD pathogenesis are changing rapidly and more investigation is required. The gut microbiota interacts with the human body by modulating the enteric and central nervous systems, and immune activity. Understanding the immune responses between gut microbiota and human body might help in elucidating the PD pathogenesis. As changes in gut microbiota composition might be associated with different clinical phenotypes of PD, gut microbiota-modulating interventions, such as probiotics and fecal microbiota transplantation (FMT), have the potential to restore the gut dysbiosis, reduce inflammation, and possibly modulate the clinical PD phenotype.

RevDate: 2021-04-21

Golob JL, K Rao (2021)

Signal vs. noise: how to analyze the microbiome and make progress on antimicrobial resistance.

The Journal of infectious diseases pii:6242384 [Epub ahead of print].

RevDate: 2021-04-21

Wang N, Yao W, Ma R, et al (2021)

The efficacy of a multistrain probiotic on cognitive function and risk of falls in patients with cirrhosis: A protocol for systematic review and meta-analysis.

Medicine, 100(16):e25535.

OBJECTIVE: The effect of probiotics on cognitive function and the risk of falling in cirrhosis patients have not been previously evaluated. We perform this protocol for systematic review and meta-analysis to evaluate the effect of a multistrain probiotic on cognitive function and the risk of falls in patients with cirrhosis.

METHODS: An all-round retrieval will be performed in 5 electronic journal databases from their inception to March 2021, which comprise Medline, Pubmed, Embase, ScienceDirect, and the Cochrane Library by 2 independent reviewers. Data extraction was performed independently, and any conflict was resolved before final analysis. Only randomized clinical trials were included in this study. The main endpoints were cognitive function and risk of falls, and the secondary endpoints were fall incidence, health-related quality of life (HRQOL), systemic inflammatory response, gut barrier, bacterial translocation, and fecal microbiota. The risk of bias assessment of the included studies was performed by 2 authors independently using the tool recommended in the Cochrane Handbook for Systematic Reviews of Interventions.

RESULTS: We hypothesized that the multistrain probiotic improved cognitive function, risk of falls, and inflammatory response in patients with cirrhosis and cognitive dysfunction.

CONCLUSION: This study expects to provide credible and scientific clinical evidence for the efficacy and safety of a multistrain probiotic on cognitive function and the risk of falls in patients with cirrhosis.

OSF REGISTRATION NUMBER: 10.17605/OSF.IO/JKMTP.

RevDate: 2021-04-21
CmpDate: 2021-04-21

Badran M, Mashaqi S, D Gozal (2020)

The gut microbiome as a target for adjuvant therapy in obstructive sleep apnea.

Expert opinion on therapeutic targets, 24(12):1263-1282.

Introduction: Gut dysbiosis is assumed to play a role in obstructive sleep apnea (OSA)-associated morbidities. Pre- and probiotics, short chain fatty acids (SCFA) and fecal matter transplantation (FMT) may offer potential as novel therapeutic strategies that target this gut dysbiosis. As more mechanisms of OSA-induced dysbiosis are being elucidated, these novel approaches are being tested in preclinical and clinical development. Areas covered: We examined the evidence linking OSA to gut dysbiosis and discuss the effects of pre- and probiotics on associated cardiometabolic, neurobehavioral and gastrointestinal disorders. The therapeutic potential of SCFA and FMT are also discussed. We reviewed the National Center for Biotechnology Information database, including PubMed and PubMed Central between 2000 - 2020. Expert opinion: To date, there are no clinical trials and only limited evidence from animal studies describing the beneficial effects of pre- and probiotic supplementation on OSA-mediated dysbiosis. Thus, more work is necessary to assess whether prebiotics, probiotics and SCFA are promising future novel strategies for targeting OSA-mediated dysbiosis.

RevDate: 2021-04-20

Zhang J, Chen Z, Yu H, et al (2021)

Anti-aging effects of a functional food via the action of gut microbiota and metabolites in aging mice.

Aging, 13: pii:202873 [Epub ahead of print].

Wushen (WS) is a mixed food containing 55 natural products that is beneficial to human health. This study aimed to reveal the preventive effect of WS on aging via a combined analysis of gut microbiome and metabolome. Senescence-accelerated mouse prone 8 (SAMP8) mice were used as aging model and senescence-accelerated mouse resistant 1 (SAMR1) mice as control. The mice were fed four diet types; control diet (for SAMR1 mice), standard diet (for SAMP8 mice, as SD group), WS diet, and fecal microbiota transplantation (FMT; transplanted from aging-WS mice). Our results showed that the weight, food intake, neurological function, and general physical conditions significantly improved in WS-fed mice compared to those fed with SD. The CA1 hippocampal region in WS-fed aged mice showed fewer shriveled neurons and increased neuronal layers compared to that of the SD group. WS-fed mice showed a decrease in malondialdehyde and an increase in superoxide dismutase levels in the brain; additionally, IL-6 and TNF-α levels significantly decreased, whereas IL-2 levels and the proportion of lymphocytes, CD3+CD8+ T, and CD4+IFNγ+T cells increased in WS-fed mice. After fed with WS, the abundance of Ruminococcus and Butyrivibrio markedly increased, whereas Lachnoclostridium and Ruminiclostridium significantly decreased in the aging mice. In addition, 887 differentially expressed metabolites were identified in fecal samples, among these, Butyrivibrio was positively correlated with D-glucuronic acid and Ruminococcus was positively associated with 5-acetamidovalerate. These findings provide mechanistic insight into the impact of WS on aging, and WS may be a valuable diet for preventing aging.

RevDate: 2021-04-19

Gal A, Barko PC, Biggs PJ, et al (2021)

One dog's waste is another dog's wealth: A pilot study of fecal microbiota transplantation in dogs with acute hemorrhagic diarrhea syndrome.

PloS one, 16(4):e0250344 pii:PONE-D-20-34770.

Canine acute hemorrhagic diarrhea syndrome (AHDS) has been associated in some studies with Clostridioides perfringens overgrowth and toxin-mediated necrosis of the intestinal mucosa. We aimed to determine the effect of a single fecal microbiota transplantation (FMT) on clinical scores and fecal microbiomes of 1 and 7 dogs with AHDS from New Zealand and South Africa. We hypothesized that FMT would improve AHDS clinical scores and increase microbiota alpha-diversity and short-chain fatty acid (SCFA)-producing microbial communities' abundances in dogs with AHDS after FMT. We sequenced the V3-V4 region of the 16S-rRNA gene in the feces of AHDS FMT-recipients and sham-treated control dogs, and their healthy donors at admission, discharge, and 30 days post-discharge. There were no significant differences in median AHDS clinical scores between FMT-recipients and sham-treated controls at admission or discharge (P = 0.22, P = 0.41). At admission, the Shannon diversity index (SDI) was lower in AHDS dogs than healthy donors (P = 0.002). The SDI did not change from admission to 30 days in sham-treated dogs yet increased in FMT-recipients from admission to discharge (P = 0.04) to levels not different than donors (P = 0.33) but significantly higher than sham-treated controls (P = 0.002). At 30 days, the SDI did not differ between FMT recipients, sham-treated controls, and donors (P = 0.88). Principal coordinate analysis of the Bray-Curtis index separated post-FMT and donor dogs from pre-FMT and sham-treated dogs (P = 0.009) because of increased SCFA-producing genera's abundances after FMT. A single co-abundance subnetwork contained many of the same OTUs found to be differentially abundant in FMT-recipients, and the abundance of this module was increased in FMT-recipients at discharge and 30 days, compared to sham-treated controls. We conclude in this small pilot study FMT did not have any clinical benefit. A single FMT procedure has the potential to increase bacterial communities of SCFA-producing genera important for intestinal health up to 30 days post-FMT.

RevDate: 2021-04-19

Gao Y, Zhang J, Xiao X, et al (2021)

The Role of Gut Microbiota in Duodenal-Jejunal Bypass Surgery-Induced Improvement of Hepatic Steatosis in HFD-Fed Rats.

Frontiers in cellular and infection microbiology, 11:640448.

Bariatric surgery including duodenal-jejunal bypass surgery (DJB) improves insulin sensitivity and reduces obesity-associated inflammation. However, the underlying mechanism for such an improvement is still incompletely understood. Our objective was to investigate the role of the gut microbiota in DJB-associated improvement of hepatic steatosis in high fat diet (HFD)-fed rats. To study this, hepatic steatosis was induced in male adult Sprague-Dawley rats by feeding them with a 60% HFD. At 8 weeks after HFD feeding, the rats were subjected to either DJB or sham operation. HFD was resumed 1 week after the surgery for 3 more weeks. In additional groups of animals, feces were collected from HFD-DJB rats at 2 weeks after DJB. These feces were then transplanted to HFD-fed rats without DJB at 8 weeks after HFD feeding. Hepatic steatosis and fecal microbiota were analyzed at 4 weeks after surgery or fecal transplantation. Our results showed that DJB alleviated hepatic steatosis in HFD-fed rats. Fecal microbiota analysis showed that HFD-fed and standard diet-fed rats clustered differently. DJB induced substantial compositional changes in the gut microbiota. The fecal microbiota of HFD-fed rats received fecal transplant from DJB rats overlapped with that of HFD-DJB rats. Treatment of rats with HFD-induced liver lesions by fecal transplant from DJB-operated HFD-fed rats also attenuated hepatic steatosis. Thus, alterations in the gut microbiota after DJB surgery are sufficient to attenuate hepatic steatosis in HFD-fed rats. Targeting the gut microbiota could be a promising approach for preventing or treating human NAFLD.

RevDate: 2021-04-19

Li F, McClain CJ, W Feng (2019)

Microbiome dysbiosis and alcoholic liver disease☆.

Liver research, 3(3-4):218-226.

Microbiome dysbiosis is strongly associated with alcoholic liver disease (ALD). Recent studies on comprehensive analyses of microbiome compositional and functional changes have begun to uncover the mechanistic relation between microbiome and the pathogenesis of ALD. Importantly, targeting the microbiome has become a potential strategy for the prevention and treatment of ALD. In this review, we summarize the clinical evidence of microbiome dysbiosis in ALD patients, and experimental advances in microbiome and metabolomic functional changes in animals with different species and genetic backgrounds in ALD. We also summarize the studies in humanized intestinal microbiome and fecal microbiota transplantation in mice. We introduce new developments in the studies on the role of the circulating bacterial microbiome, oral bacterial microbiome and fungal microbiome in the development of ALD. We highlight the potential mechanisms by which microbiome dysbiosis contributes to ALD, including short chain fatty acid changes, bile acid metabolism, intestinal barrier function, release of bacterial and fungal products, and inflammation. In addition, we summarize the recent developments targeting the microbiome in prevention and treatment of ALD, including dietary nutrient interference, herbal medicine, antibiotics, anti-fungal agents, probiotics, engineered bacterial therapy, fecal transplantation and oral hygiene. Although recent preclinical studies have advanced our understanding of the microbiome and ALD, clinical studies, especially prospective studies with large samples, are needed to better understand the cause-effect of microbiome dysbiosis in ALD. Identifying new precision-based strategies targeting the microbiome are expected to be developed as more effective therapies in ALD.

RevDate: 2021-04-17

Pomares Bascuñana RÁ, Veses V, CC Sheth (2021)

Effectiveness of fecal microbiota transplant for the treatment of Clostridioides difficile diarrhea: A systematic review and meta-analysis.

Letters in applied microbiology [Epub ahead of print].

Clostridioides difficile is a major cause of health-care related infections and antibiotic-associated diarrhea. High recurrence rates following antibiotic treatment, along with the emergence of hypervirulent and multidrug resistant ribotypes makes essential the development of safe, effective, novel therapies for the treatment of C. difficile infections. The primary outcome evaluated in this meta-analysis was the effectiveness of fecal microbiota transplantation (FMT). Secondary outcomes were the proportion of patients suffering adverse effects along with the most effective administration route. The mean treatment effectiveness was 82% (95% CI: 75-89). Overall, patients receiving FMT via colonoscopy experienced more adverse effects than patients whom received enema, or oral capsules (71.6 % versus 40.2 %, and 35.3% respectively). Comparing administration of FMT by colonoscopy versus enema resulted in a Hedges' g of -0.74 (95% CI of -0.9 - -0.58), indicating a slight advantage in favor of colonoscopy. The comparison between colonoscopy and capsule returned a Hedges' g of 0.44 (95% CI of 0.20 - 0.69), indicating that delivery of the FMT by capsule was statistically significantly more effective. FMT provides an effective and safe treatment for C. difficile diarrhea. Further research into the efficacy of different preparation protocols is needed.

RevDate: 2021-04-19

Li X, Su C, Jiang Z, et al (2021)

Berberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-N-oxide production via manipulating the gut microbiome.

NPJ biofilms and microbiomes, 7(1):36.

Trimethylamine-N-oxide (TMAO), a derivative from the gut microbiota metabolite trimethylamine (TMA), has been identified to be an independent risk factor for promoting atherosclerosis. Evidences suggest that berberine (BBR) could be used to treat obesity, diabetes and atherosclerosis, however, its mechanism is not clear mainly because of its poor oral bioavailability. Here, we show that BBR attenuated TMA/TMAO production in the C57BL/6J and ApoE KO mice fed with choline-supplemented chow diet, and mitigated atherosclerotic lesion areas in ApoE KO mice. Inhibition of TMA/TMAO production by BBR-modulated gut microbiota was proved by a single-dose administration of d9-choline in vivo. Metagenomic analysis of cecal contents demonstrated that BBR altered gut microbiota composition, microbiome functionality, and cutC/cntA gene abundance. Furthermore, BBR was shown to inhibit choline-to-TMA conversion in TMA-producing bacteria in vitro and in gut microbial consortium from fecal samples of choline-fed mice and human volunteers, and the result was confirmed by transplantation of TMA-producing bacteria in mice. These results offer new insights into the mechanisms responsible for the anti-atherosclerosis effects of BBR, which inhibits commensal microbial TMA production via gut microbiota remodeling.

RevDate: 2021-04-19

Albuhairi S, R Rachid (2021)

Biologics and Novel Therapies for Food Allergy.

Immunology and allergy clinics of North America, 41(2):271-283.

Food allergy is a significant public health burden affecting around 10% of adults and 8% of children. Although the first peanut oral immunotherapy product received Food and Drug Administration approval in 2020, there is still an unmet need for more effective therapeutic options that minimize the risk of anaphylaxis, nutritional deficiencies, and patient's quality of life. Biologics are promising modalities, as they may improve compliance, target multiple food allergies, and treat other concomitant atopic diseases. Although omalizumab has been evaluated extensively, most biologics are more novel and have broader immunologic impact. Careful evaluation of their safety profile should therefore be conducted.

RevDate: 2021-04-15

Wang Q, Luo Y, Chaudhuri KR, et al (2021)

The role of gut dysbiosis in Parkinson's disease: mechanistic insights andtherapeutic options.

Brain : a journal of neurology pii:6226389 [Epub ahead of print].

Parkinson's disease is a common neurodegenerative disease in which gastrointestinal symptoms may appear prior to motor symptoms. The gut microbiota of patients with Parkinson's disease shows unique changes, which may be used as early biomarkers of disease. Alteration in gut microbiota composition may be related to the cause or effect of motor or non-motor symptoms, but the specific pathogenic mechanisms are unclear. The gut microbiota and its metabolites have been suggested to be involved in the pathogenesis of Parkinson's disease by regulating neuroinflammation, barrier function and neurotransmitter activity. There is bidirectional communication between the enteric nervous system and the central nervous system, and the microbiota-gut-brain axis may provide a pathway for the transmission of α-synuclein. We highlight recent discoveries and alterations of the gut microbiota in Parkinson's disease, and highlight current mechanistic insights on the microbiota-gut-brain axis in disease pathophysiology. We discuss the interactions between production and transmission of α-synuclein and gut inflammation and neuroinflammation. In addition, we also draw attention to diet modification, use of probiotics and prebiotics and fecal microbiota transplantation as potential therapeutic approaches that may lead to a new treatment paradigm for Parkinson's disease.

RevDate: 2021-04-16
CmpDate: 2021-04-16

Ballif A, Gerber S, Carrez L, et al (2021)

[Fecal microbiota transplantation: from the evidence to the realty of the field].

Revue medicale suisse, 17(734):726-731.

In clinical practice, fecal microbiota transplantation (FMT) has been established as an unparalleled therapy to date for multiple recurrent Clostridioides difficile infections (CDI). The implementation of the FMT in practice requires a significant investment to meet legal, security and financial requirements. Research on the microbiota is booming and multiple investigations on FMT in indications other than CDI are ongoing.

RevDate: 2021-04-14

Cappetto CM (2021)

Successful use of early, repeat fecal microbiota transplantation for initial treatment of severe, refractory Clostridioides difficile colitis.

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists pii:6225235 [Epub ahead of print].

DISCLAIMER: In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

PURPOSE: There is a paucity of literature surrounding the use of early fecal microbiota transplantation (FMT) for patients presenting with an initial episode of severe, refractory Clostridioides difficile infection (CDI). Information on optimal antibiotic dosing and therapy duration surrounding FMT during an acute, initial episode of CDI is also limited. Described here is a case of successful treatment of CDI after 4 FMTs during an acute, initial episode of severe, refractory Clostridioides difficile colitis.

SUMMARY: A 69-year-old community-dwelling, Caucasian male presented after 48 hours of vomiting and diarrhea. A stool sample tested positive via stool sample by both polymerase chain reaction and enzme-linked immunosorbent assays for Clostridioides difficile. The patient was treated with several days of oral and rectal vancomycin therapy in addition to intravenous metronidazole, but those treatments failed. His clinical and nutrition status deteriorated over the course of several days until salvage therapy was ordered, with administration of 1 inpatient nasogastric FMT and 1 inpatient colonoscopic FMT followed by outpatient colonoscopic FMTs on 2 consecutive days within 2 weeks of hospital discharge.

CONCLUSION: This case suggests a role for early, repeat FMT during an initial presentation of a severe Clostridioides difficile colitis episode refractory to pharmacologic antimicrobial therapy. It also adds to emerging literature regarding the timing of antibiotic cessation surrounding FMT.

RevDate: 2021-04-12

Monaghan TM, Seekatz AM, Markham NO, et al (2021)

Fecal microbiota transplantation for recurrent Clostridioides difficile infection associates with functional alterations in circulating microRNAs.

Gastroenterology pii:S0016-5085(21)00577-1 [Epub ahead of print].

BACKGROUND AND AIMS: The molecular mechanisms underlying successful fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (rCDI) remain poorly understood. The primary objective of this study was to characterize alterations in microRNAs (miRs) following FMT for rCDI.

METHODS: Sera from two prospective multicentre randomized controlled trials were analyzed for miRNA levels using the Nanostring nCounter platform and quantitative RT-PCR. Additionally, rCDI-FMT and toxin-treated animals and ex vivo human colonoids were employed to compare intestinal tissue and circulating miRNAs. miRNA inflammatory gene targets in colonic epithelial and peripheral blood mononuclear cells were evaluated by qPCR and 3'UTR reporter assays. Colonic epithelial cells were employed for mechanistic, cytoskeleton, cell growth and apoptosis studies.

RESULTS: miRNA profiling revealed upregulation of 64 circulating miRNAs 4- and 12-weeks following FMT compared to screening, of which the top 6 were validated in the discovery cohort by RT-qPCR. In a murine model of relapsing-CDI, RT-qPCR analyses of sera and cecal RNA extracts demonstrated suppression of these miRNAs, an effect reversed by FMT. In mouse colon and human colonoids, TcdB mediated the suppressive effects of CDI on miRNAs. CDI dysregulated Drosha, an effect reversed by FMT. Correlation analyses, qPCR and 3'UTR reporter assays revealed that miR-23a, miR-150, miR-26b, miR-28 target directly the 3'UTR of IL12B, IL18, FGF21 and TNFRSF9, respectively. miR-23a and miR-150 demonstrated cytoprotective effects against TcdB.

CONCLUSION: These results provide novel and provocative evidence that modulation of the gut microbiome via FMT induces alterations in circulating and intestinal tissue miRNAs. These findings contribute to a greater understanding of the molecular mechanisms underlying FMT and identify new potential targets for therapeutic intervention in rCDI.

RevDate: 2021-04-12

Madsen M, Kimer N, Bendtsen F, et al (2021)

Fecal microbiota transplantation in hepatic encephalopathy: a systematic review.

Scandinavian journal of gastroenterology [Epub ahead of print].

Hepatic encephalopathy (HE) is a reversible neurocognitive dysfunction that ranges in severity from subclinical alterations to coma. Patients with chronic liver disease are predisposed to HE due to metabolic failure and portosystemic shunting of toxins, of which ammonia is believed to be the main toxic chemical. Fecal microbiota transplantation (FMT) may reduce ammonia synthesis by altering the gut microbiota composition to a taxon low in urease, diminish uptake of ammonia by reestablishing the integrity of the intestinal barrier and increase ammonia clearance by improving liver function. In this systematic review, we summarize the insights of the current literature examining FMT as a treatment for HE.PubMed and EMBASE were searched on 08 February 2021 using the MeSH terms 'fecal microbiota transplantation & hepatic encephalopathy' and the abbreviations 'FMT & HE'.Eight studies fulfilled our inclusion criteria, comprising two randomized clinical trials, three case reports and three rodent studies. Thirty-nine patients with HE were treated with FMT. Thirty-nine rodents received FMT in laboratory tests. FMT improved neurocognitive test results in four human studies and two rodent studies. Microbiota originating from donors was found in human recipients one year post-FMT. Readmission of patients was lower after treatment with FMT compared to standard of care.FMT may improve neurocognitive function and reduce serious adverse events in patients with HE, but the studies conducted so far have been small and their long-term follow-up is limited. Large-scale, randomized and controlled trials are needed to validate and help standardize the clinical application of FMT in cases of HE.

RevDate: 2021-04-16

Björkqvist O, Rangel I, Serrander L, et al (2021)

Faecalibacterium prausnitzii increases following fecal microbiota transplantation in recurrent Clostridioides difficile infection.

PloS one, 16(4):e0249861.

OBJECTIVE: Fecal microbiota transplantation (FMT) is a highly effective treatment for Clostridioides difficile infection (CDI). However, the fecal transplant's causal components translating into clearance of the CDI are yet to be identified. The commensal bacteria Faecalibacterium prausnitzii may be of great interest in this context, since it is one of the most common species of the healthy gut microbiota and produces metabolites with anti-inflammatory properties. Although there is mounting evidence that F. prausnitzii is an important regulator of intestinal homeostasis, data about its role in CDI and FMT are relatively scarce.

METHODS: Stool samples from patients with recurrent CDI were collected to investigate the relative abundance of F. prausnitzii before and after FMT. Twenty-one patients provided fecal samples before the FMT procedure, at 2 weeks post-FMT, and at 2-4 months post-FMT. The relative abundance of F. prausnitzii was determined using quantitative polymerase chain reaction.

RESULTS: The abundance of F. prausnitzii was elevated in samples (N = 9) from donors compared to pre-FMT samples (N = 15) from patients (adjusted P<0.001). No significant difference in the abundance of F. prausnitzii between responders (N = 11) and non-responders (N = 4) was found before FMT (P = 0.85). In patients with CDI, the abundance of F. prausnitzii significantly increased in the 2 weeks post-FMT samples (N = 14) compared to the pre-FMT samples (N = 15, adjusted P<0.001). The increase persisted 2-4 months post-FMT (N = 15) compared to pre-FMT samples (N = 15) (adjusted P<0.001).

CONCLUSIONS: FMT increases the relative abundance of F. prausnitzii in patients with recurrent CDI, and this microbial shift remains several months later. The baseline abundance of F. prausnitzii in donors or recipients was not associated with future treatment response, although a true predictive capacity cannot be excluded because of the limited sample size. Further studies are needed to discern whether F. prausnitzii plays an active role in the resolution of CDI.

RevDate: 2021-04-11

Grigoryan Z, Shen MJ, Twardus SW, et al (2020)

Fecal microbiota transplantation: Uses, questions, and ethics.

Medicine in microecology, 6:.

Fecal microbiota transplantation (FMT) has rapidly grown in notoriety and popularity worldwide as a treatment for both recurrent and refractory C. difficile infection (CDI), as well as for a myriad of other indications, with varying levels of evidence to justify its use. At present, FMT use in the U.S. has not received marketing approval from the U.S. Food and Drug Administration (FDA), but is permitted under "enforcement discretion" for CDI not responding to standard therapy. Meanwhile, the rising interest in the gut microbiome throughout mainstream media has paved the way for "do-it-yourself" (DIY) adaptations of the procedure. This access and unregulated use, often outside any clinical supervision, has quickly outpaced the medical community's research and regulatory efforts. While some studies have been able to demonstrate the success of FMT in treating conditions other than CDI-studies on ulcerative colitis have been particularly promising-little is still known about the treatmen's mechanism of action or long-term side effects. Likewise, screening of donor stool is in its early stages in terms of protocol standardization. In this paper, we explore the regulatory and ethical concerns that arise from the need to balance access to a nascent but promising innovative treatment with the need for research into its efficacy, risk profile, and long-term impact.

RevDate: 2021-04-15
CmpDate: 2021-04-15

Fang S, Wu S, Ji L, et al (2021)

The combined therapy of fecal microbiota transplantation and laxatives for functional constipation in adults: A systematic review and meta-analysis of randomized controlled trials.

Medicine, 100(14):e25390.

OBJECTIVE: Functional constipation is a prevalent, burdensome gastrointestinal disorder whose treatment remains challenging. Combined therapy uniting multiple treatments may be promising. Fecal microbiota transplantation (FMT) which tends to be an etiological treatment has been increasingly investigated in its management. Meanwhile, laxatives are widely used to relieve constipation temporarily, but their overall efficacy is poor. Therefore, we performed meta-analyses of randomized controlled trials to evaluate the joint efficacy of FMT and laxatives in functional constipation.

METHODS: We performed a systematic literature search of 6 electronic databases as of August 11, 2020. Randomized controlled trial of FMT together with laxatives vs laxatives alone in functional constipation in adults were included. Two reviewers independently performed the screening, data extraction, and bias assessment. Dichotomous outcome data were synthesized by risk ratio, and measurement data by weighted mean difference (WMD).

RESULTS: A total of 1400 records were identified, of which 5 were eligible (409 patients). Overall, compared to laxatives alone, combined therapy of FMT and laxatives more significantly improved total effective rate (risk ratio: 1.35; 95% confidence interval [CI]: 1.14, 1.60; I2 = 13%), Bristol stool form scale score (WMD: 1.04; 95% CI: 0.57, 1.51; I2 = 76%), reduce Wexner score (WMD: -3.25; 95% CI: -5.58, -0.92; I2 = 92%), Knowles-Eccersley-Scott-Symptom (KESS) score (WMD: -5.65; 95% CI: -7.62, -3.69; I2 = 0%) and patient assessment of constipation quality of life score (WMD: -18.56; 95%; CI: -26.43, -10.68; I2 = 78%). No serious adverse events were reported. The majority of included studies had poor methodological quality.

CONCLUSION: Combined therapy of FMT and laxatives may be a reasonably effective and safe treatment for people with functional constipation. However, caution is needed with the interpretation of these data due to the small sample size, high heterogeneity, and low quality of the studies. Besides, we expect that more studies will be performed exploring the efficacy and safety of combined therapy for functional constipation.

RevDate: 2021-04-08

Dixon CE, Bedenice D, Restifo M, et al (2021)

NEONATAL INTENSIVE CARE OF 10 HOSPITALIZED GIRAFFE CALVES (GIRAFFA CAMELOPARDALIS) REQUIRING HAND-REARING.

Journal of zoo and wildlife medicine : official publication of the American Association of Zoo Veterinarians, 52(1):57-66.

This retrospective case series describes the clinicopathologic findings, diagnoses, treatment, and outcomes of 10 hand-reared newborn giraffe (Giraffa camelopardalis) calves admitted to a university teaching hospital for intensive care. Ten calves (five males, five females; nine reticulated giraffes [Giraffa camelopardalis reticulata], one Masai giraffe [G. c. tippelskirchi]), were admitted under 2 days of age. Inadequate transfer of passive immunity was suspected in 5 of 10 calves based on assessment of serum total solids and globulin values. These calves were treated with oral frozen bovine colostrum and/or intravenous hyperimmune bovine plasma. Diarrhea occurred in 6 of 10 calves and was managed with supportive care, fecal microbiota transplantation, and limiting milk intake (offering 10% body weight [BW] in milk per day, while feeding <2 L per meal at 2- to 4-hr intervals). Less common diagnoses included pneumonia (n = 3) and mycoplasma-associated septic arthritis (n = 1). Eight calves received systemic antimicrobial therapy. Hyperlactatemia (lactate > 5 mmol/L; n = 8) and hypercreatininemia (creatinine > 2.0 mg/dl, n = 7) were the most common presenting laboratory abnormalities, which resolved with intravenous fluid therapy. All neonatal giraffes survived to discharge after a median hospitalization of 9.5 days (range, 5-37 days) and were successfully hand-reared at their place of birth. In conclusion, neonatal giraffe calves can be intensively managed in a hospital environment. Diarrhea was a common clinical problem and can be related to feeding regimens. Intravenous hyperimmune bovine plasma infusion was well tolerated to manage failure of transfer of passive immunity in calves with inadequate colostrum administration. The current study supports that compromised neonatal giraffe calves may carry an excellent prognosis after early, intensive intervention.

RevDate: 2021-04-08

Park SY, GS Seo (2021)

Fecal Microbiota Transplantation: Is It Safe?.

Clinical endoscopy, 54(2):157-160.

Fecal microbiota transplantation (FMT) is an accepted procedure for the management of recurrent Clostridioides difficile infections. FMT is generally considered safe and well-tolerated - even in high-risk patients. Most short-term risks are mild and known to be associated with delivery methods. Long-term side effects have not been established, and no signs of harm have been found to date. However, causality for several microbiome-associated diseases has to be established. Even though FMT is generally considered safe with strict donor screening, serious adverse events have been recently associated with the FMT product from the stool bank, where screening for multi-drug resistant organisms is not included in protocols. Here, we discuss the adverse events associated with FMT and safety issues.

RevDate: 2021-04-07

Xiao L, Yan J, Yang T, et al (2021)

Fecal Microbiome Transplantation from Children with Autism Spectrum Disorder Modulates Tryptophan and Serotonergic Synapse Metabolism and Induces Altered Behaviors in Germ-Free Mice.

mSystems, 6(2):.

To determine the relationship of the gut microbiota and its metabolites with autism spectrum disorder (ASD)-like behaviors and preliminarily explore the potential molecular mechanisms, the fecal microbiota from donors with ASD and typically developing (TD) donors were transferred into germ-free (GF) mice to obtain ASD-FMT mice and TD-FMT mice, respectively. Behavioral tests were conducted on these mice after 3 weeks. 16S rRNA gene sequencing of the cecal contents and untargeted metabolomic analysis of the cecum, serum, and prefrontal cortex were performed. Untargeted metabolomics was also used to analyze fecal samples of TD and ASD children. Western blotting detected the protein expression levels of tryptophan hydroxylase 1 (TPH1), serotonin transporter (SERT), and serotonin 1A receptor (5-HT1AR) in the colon and TPH2, SERT, and 5-HT1AR in the prefrontal cortex of mice. ASD-FMT mice showed ASD-like behavior and a microbial community structure different from that of TD-FMT mice. Tryptophan and serotonin metabolisms were altered in both ASD and TD children and ASD-FMT and TD-FMT mice. Some microbiota may be related to tryptophan and serotonin metabolism. Compared with TD-FMT mice, ASD-FMT mice showed low SERT and 5-HT1AR and high TPH1 expression levels in the colon. In the prefrontal cortex, the expression levels of TPH2 and SERT were increased in the ASD-FMT group relative to the TD-FMT group. Therefore, the fecal microbiome of ASD children can lead to ASD-like behaviors, different microbial community structures, and altered tryptophan and serotonin metabolism in GF mice. These changes may be related to changes in some key proteins involved in the synthesis and transport of serotonin.IMPORTANCE The relationship between the gut microbiota and ASD is not yet fully understood. Numerous studies have focused on the differences in intestinal microbial and metabolism profiles between TD and ASD children. However, it is still not clear if these microbes and metabolites cause the development of ASD symptoms. Here, we collected fecal samples from TD and ASD children, transplanted them into GF mice, and found that the fecal microbiome of ASD children can lead to ASD-like behaviors, different microbial community structures, and altered tryptophan and serotonin metabolism in GF mice. We also demonstrated that tryptophan and serotonin metabolism was also altered in ASD and TD children. Together, these findings confirm that the microbiome from children with ASD may lead to ASD-like behavior of GF mice through metabolites, especially tryptophan and serotonin metabolism.

RevDate: 2021-04-11

Wang F, Song M, Lu X, et al (2021)

Gut microbes in gastrointestinal cancers.

Seminars in cancer biology pii:S1044-579X(21)00098-5 [Epub ahead of print].

Gut microbes (GMs), dominated by bacteria, play important roles in many physiological processes. The structures and functions of GMs are closely related to human health, the occurrence and development of diseases and the rapid recovery of the body. Gastrointestinal cancers are the major diseases affecting human health worldwide. With the development of metagenomic technology and the wide application of new generation sequencing technology, a large number of studies suggest that complex GMs are related to the occurrence and development of gastrointestinal cancers. Fecal microbiota transplantation (FMT) and probiotics can treat and prevent the occurrence of gastrointestinal cancers. This article reviews the latest research progress of microbes in gastrointestinal cancers from the perspectives of the correlation, the influence mechanism and the application, so as to provide new directions for the prevention, early diagnosis and treatment of gastrointestinal cancers.

RevDate: 2021-04-16
CmpDate: 2021-04-16

Kazemian N, Kao D, S Pakpour (2021)

Fecal Microbiota Transplantation during and Post-COVID-19 Pandemic.

International journal of molecular sciences, 22(6):.

COVID-19 is a major pandemic facing the world today, which has implications on current microbiome-based treatments such as fecal microbiota transplantation (FMT) used for recurrent Clostridioides difficile infections. The bidirectional relationship between the inhabitants of our gut, the gut microbiota, and COVID-19 pathogenesis, as well as the underlying mechanism involved, must be elucidated in order to increase FMT safety and efficacy. In this perspective, we discuss the crucial cross-talk between the gut microbiota and the lungs, known as the gut-lung axis, during COVID-19 infection, as well as the putative effect of these microorganisms and their functional activity (i.e., short chain fatty acids and bile acids) on FMT treatment. In addition, we highlight the urgent need to investigate the possible impact of COVID-19 on FMT safety and efficacy, as well as instilling stringent screening protocols of donors and recipients during COVID-19 and post-COVID-19 pandemic to produce a cohesive and optimized FMT treatment plan across all centers and in all countries across the globe.

RevDate: 2021-04-13

Basson AR, Cominelli F, A Rodriguez-Palacios (2021)

'Statistical Irreproducibility' Does Not Improve with Larger Sample Size: How to Quantify and Address Disease Data Multimodality in Human and Animal Research.

Journal of personalized medicine, 11(3):.

Poor study reproducibility is a concern in translational research. As a solution, it is recommended to increase sample size (N), i.e., add more subjects to experiments. The goal of this study was to examine/visualize data multimodality (data with >1 data peak/mode) as cause of study irreproducibility. To emulate the repetition of studies and random sampling of study subjects, we first used various simulation methods of random number generation based on preclinical published disease outcome data from human gut microbiota-transplantation rodent studies (e.g., intestinal inflammation and univariate/continuous). We first used unimodal distributions (one-mode, Gaussian, and binomial) to generate random numbers. We showed that increasing N does not reproducibly identify statistical differences when group comparisons are repeatedly simulated. We then used multimodal distributions (>1-modes and Markov chain Monte Carlo methods of random sampling) to simulate similar multimodal datasets A and B (t-test-p = 0.95; N = 100,000), and confirmed that increasing N does not improve the 'reproducibility of statistical results or direction of the effects'. Data visualization with violin plots of categorical random data simulations with five-integer categories/five-groups illustrated how multimodality leads to irreproducibility. Re-analysis of data from a human clinical trial that used maltodextrin as dietary placebo illustrated multimodal responses between human groups, and after placebo consumption. In conclusion, increasing N does not necessarily ensure reproducible statistical findings across repeated simulations due to randomness and multimodality. Herein, we clarify how to quantify, visualize and address disease data multimodality in research. Data visualization could facilitate study designs focused on disease subtypes/modes to help understand person-person differences and personalized medicine.

RevDate: 2021-04-05

Pham VT, Calatayud M, Rotsaert C, et al (2021)

Antioxidant Vitamins and Prebiotic FOS and XOS Differentially Shift Microbiota Composition and Function and Improve Intestinal Epithelial Barrier In Vitro.

Nutrients, 13(4): pii:nu13041125.

Human gut microbiota (HGM) play a significant role in health and disease. Dietary components, including fiber, fat, proteins and micronutrients, can modulate HGM. Much research has been performed on conventional prebiotics such as fructooligosaccharides (FOS) and galactooligosaccharides (GOS), however, novel prebiotics or micronutrients still require further validation. We assessed the effect of FOS, xylooligosaccharides (XOS) and a mixture of an antioxidant vitamin blend (AOB) on gut microbiota composition and activity, and intestinal barrier in vitro. We used batch fermentations and tested the short-term effect of different products on microbial activity in six donors. Next, fecal inocula from two donors were used to inoculate the simulator of the human microbial ecosystem (SHIME) and after long-term exposure of FOS, XOS and AOB, microbial activity (short- and branched-chain fatty acids and lactate) and HGM composition were evaluated. Finally, in vitro assessment of intestinal barrier was performed in a Transwell setup of differentiated Caco-2 and HT29-MTX-E12 cells exposed to fermentation supernatants. Despite some donor-dependent differences, all three tested products showed beneficial modulatory effects on microbial activity represented by an increase in lactate and SCFA levels (acetate, butyrate and to a lesser extent also propionate), while decreasing proteolytic markers. Bifidogenic effect of XOS was consistent, while AOB supplementation appears to exert a specific impact on reducing F. nucleatum and increasing butyrate-producing B. wexlerae. Functional and compositional microbial changes were translated to an in vitro host response by increases of the intestinal barrier integrity by all the products and a decrease of the redox potential by AOB supplementation.

RevDate: 2021-04-05

Schmidt EKA, Raposo PJF, Madsen KL, et al (2021)

What Makes a Successful Donor? Fecal Transplant from Anxious-Like Rats Does Not Prevent Spinal Cord Injury-Induced Dysbiosis.

Biology, 10(4): pii:biology10040254.

Spinal cord injury (SCI) causes gut dysbiosis and an increased prevalence of depression and anxiety. Previous research showed a link between these two consequences of SCI by using a fecal transplant from healthy rats which prevented both SCI-induced microbiota changes and the subsequent development of anxiety-like behaviour. However, whether the physical and mental state of the donor are important factors in the efficacy of FMT therapy after SCI remains unknown. In the present study, rats received a fecal transplant following SCI from uninjured donors with increased baseline levels of anxiety-like behaviour and reduced proportion of Lactobacillus in their stool. This fecal transplant increased intestinal permeability, induced anxiety-like behaviour, and resulted in minor but long-term alterations in the inflammatory state of the recipients compared to vehicle controls. There was no significant effect of the fecal transplant on motor recovery in rehabilitative training, suggesting that anxiety-like behaviour did not affect the motivation to participate in rehabilitative therapy. The results of this study emphasize the importance of considering both the microbiota composition and the mental state of the donor for fecal transplants following spinal cord injury.

RevDate: 2021-04-08

Mocanu V, Rajaruban S, Dang J, et al (2021)

Repeated Fecal Microbial Transplantations and Antibiotic Pre-Treatment Are Linked to Improved Clinical Response and Remission in Inflammatory Bowel Disease: A Systematic Review and Pooled Proportion Meta-Analysis.

Journal of clinical medicine, 10(5):.

The response of patients with inflammatory bowel disease (IBD) to fecal microbial transplantation (FMT) has been inconsistent possibly due to variable engraftment of donor microbiota. This failure to engraft has resulted in the use of several different strategies to attempt optimization of the recipient microbiota following FMT. The purpose of our study was to evaluate the effects of two distinct microbial strategies-antibiotic pre-treatment and repeated FMT dosing-on IBD outcomes. A systematic literature review was designed and implemented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A medical librarian conducted comprehensive searches in MEDLINE, Embase, Scopus, Web of Science Core Collection, and Cochrane Library on 25 November 2019 and updated on 29 January 2021. Primary outcomes of interest included comparing relapse and remission rates in patients with IBD for a single FMT dose, repeated FMT dosages, and antibiotic pre-treatment groups. Twenty-eight articles (six randomized trials, 20 cohort trials, two case series) containing 976 patients were identified. Meta-analysis revealed that both repeated FMT and antibiotic pre-treatment strategies demonstrated improvements in pooled response and remission rates. These clinical improvements were associated with increases in fecal microbiota richness and α-diversity, as well as the enrichment of several short-chain fatty acid (SCFA)-producing anaerobes including Bifidobacterium, Roseburia, Lachnospiraceae, Prevotella, Ruminococcus, and Clostridium related species.

RevDate: 2021-04-13

Lorente-Picón M, A Laguna (2021)

New Avenues for Parkinson's Disease Therapeutics: Disease-Modifying Strategies Based on the Gut Microbiota.

Biomolecules, 11(3):.

Parkinson's disease (PD) is a multifactorial neurodegenerative disorder that currently affects 1% of the population over the age of 60 years, and for which no disease-modifying treatments exist. Neurodegeneration and neuropathology in different brain areas are manifested as both motor and non-motor symptoms in patients. Recent interest in the gut-brain axis has led to increasing research into the gut microbiota changes in PD patients and their impact on disease pathophysiology. As evidence is piling up on the effects of gut microbiota in disease development and progression, another front of action has opened up in relation to the potential usage of microbiota-based therapeutic strategies in treating gastrointestinal alterations and possibly also motor symptoms in PD. This review provides status on the different strategies that are in the front line (i.e., antibiotics; probiotics; prebiotics; synbiotics; dietary interventions; fecal microbiota transplantation, live biotherapeutic products), and discusses the opportunities and challenges the field of microbiome research in PD is facing.

RevDate: 2021-04-13

Ooijevaar RE, van Nood E, Goorhuis A, et al (2021)

Ten-Year Follow-Up of Patients Treated with Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection from a Randomized Controlled Trial and Review of the Literature.

Microorganisms, 9(3):.

Fecal microbiota transplantation (FMT) has become a well-established treatment for recurrent Clostridioides difficile infection (rCDI). While short-term outcomes and adverse events relating to FMT have been well documented, there still is a paucity of data with regard to long-term safety. In this report, we describe the long-term follow-up of the prospective cohort of the first randomized controlled trial of FMT for rCDI, and review the existing literature. A total of 34 patients were treated with FMT for rCDI. Seven patients were still alive after a follow-up of more than 10 years and three patients were lost to follow-up. None of the 34 patients had experienced a new-onset autoimmune, gastrointestinal, or malignant disorder during follow-up. We did not find any deterioration or amelioration of pre-existing medical conditions. Furthermore, no deaths directly attributable to FMT could be identified. These findings are in accordance with the data in available literature. In conclusion, no long-term adverse events or complications directly attributable to FMT were found in our prospective cohort. Review of the available literature does not point to long-term risks associated with FMT in this elderly population, provided that carefully screened fecal suspensions are being used. No firm conclusion on the long-term safety of FMT in younger patients could be drawn.

RevDate: 2021-04-02

Leung J, S Pham (2021)

A Systematic Review of Fecal Microbiota Transplantation Versus Vancomycin for Treatment of Recurrent Clostridioides difficile Infection.

Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates, 44(2):106-115.

Clostridioides difficile infection is a major clinical challenge, which may be associated with severe complications. Clostridioides difficile infection may result in repeated episodes of diarrhea, abdominal pain, and dehydration, leading to an increased risk of mortality. Increasingly high rates of recurrent Clostridioides difficile-associated diarrhea, refractory to antibiotic therapy, are difficult to treat. The suboptimal response to antibiotic therapy has led to the need for fecal microbiota transplantation in addition to the more commonly prescribed antibiotic, vancomycin. This systematic review aims to evaluate the effectiveness of fecal microbiota transplantation in the resolution of recurrent Clostridioides difficile infection in adults, compared with an oral vancomycin regimen alone. A systematic literature search was performed, resulting in three randomized control studies. Results from the studies are conflicting, with different variations of study outcomes. In two of the three randomized control trials, fecal microbiota transplantation was statistically significant in effectively resolving Clostridioides difficile infection, but not significant in the third. Although fecal microbiota transplantation results are promising, there are many different variables within the studies, and further research is recommended to explore the effects of these variables within larger sample sizes.

RevDate: 2021-04-17

Manrique P, Zhu Y, van der Oost J, et al (2021)

Gut bacteriophage dynamics during fecal microbial transplantation in subjects with metabolic syndrome.

Gut microbes, 13(1):1-15.

Metabolic Syndrome (MetS) is a growing public health concern worldwide. Individuals with MetS have an increased risk for cardiovascular (CV) disease and type 2 diabetes (T2D). These diseases - in part preventable with the treatment of MetS - increase the chances of premature death and pose a great economic burden to health systems. A healthy gut microbiota is associated with a reduction in MetS, T2D, and CV disease. Treatment of MetS with fecal microbiota transplantation (FMT) can be effective, however, its success rate is intermediate and difficult to predict. Because bacteriophages significantly affect the microbiota membership and function, the aim of this pilot study was to explore the dynamics of the gut bacteriophage community after FMT in MetS subjects. We performed a longitudinal study of stool bacteriophages from healthy donors and MetS subjects before and after FMT treatment. Subjects were assigned to either a control group (self-stool transplant, n = 3) or a treatment group (healthy-donor-stool transplant; n-recipients = 6, n-donors = 5). Stool samples were collected over an 18-week period and bacteriophage-like particles were purified and sequenced. We found that FMT from healthy donors significantly alters the gut bacteriophage community. Subjects with better clinical outcome clustered closer to the heathy donor group, suggesting that throughout the treatment, their bacteriophage community was more similar to healthy donors. Finally, we identified bacteriophage groups that could explain these differences and we examined their prevalence in individuals from a larger cohort of MetS FMT trial.Trial information- http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2705; NTR 2705.

RevDate: 2021-04-01

Qian Q, He W, Tang R, et al (2021)

Implications of gut microbiota in autoimmune liver diseases.

Minerva gastroenterology pii:S2724-5985.21.02860-9 [Epub ahead of print].

Autoimmune liver diseases (AILD) is a group of immune-mediated liver inflammatory diseases with three major forms including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Interaction of both genetic and environmental factors leads to the breakdown of self-tolerance, hence resulting in hyper-responsive of autoantibodies and aggressive autoreactive immune cells. Genetic studies have identified dozens of risk loci associated with initiation and development of AILD. However, the role of exogenous factors remains unclear. Recently, both infectious and inflammatory diseases have been associated with microbiota, which colonizes multiple mucosal surfaces and participates in human physiological process and function in immune system, particularly influencing liver and biliary system via gut-liver axis. Emerging evidence on the role of gut microbiota has expanded our knowledge of AILD in both pathogenesis and potential therapeutic targets, along with putative diagnosis biomarkers. Herein we review the relationship between host and gut microbiota, discuss their potential roles in disease onset and progression, and summarize the compositional and functional alterations of the microbiota in AILD. We also highlight the microbiotabased therapeutics such as antibiotics and fecal microbiota transplantation (FMT).

RevDate: 2021-03-31

Bui TPN, WM de Vos (2021)

Next-generation therapeutic bacteria for treatment of obesity, diabetes, and other endocrine diseases.

Best practice & research. Clinical endocrinology & metabolism pii:S1521-690X(21)00021-X [Epub ahead of print].

The human gut microbiota has appeared as an important factor affecting host health and intestinal bacteria have recently emerged as potential therapeutics to treat diabetes and other endocrine diseases. These mainly anaerobic bacteria have been identified either via comparative "omics" analysis of the intestinal microbiota in healthy and diseased subjects or of data collected by fecal microbiota transplantation studies. Both approaches require advanced and in-depth sequencing technologies to perform massive genomic screening to select bacteria with potential benefits. It has been shown that these potentially therapeutic bacteria can either produce bioactive products that directly influence the host patho-physiology and endocrine systems or produce specific signaling molecules that may do so. These bioactive compounds can be formed via degradation of dietary or host-derived components or the conversion of intermediate compounds produced by fermentation of intestinal bacteria. Several of these bacteria have shown causality in preclinical models and entered clinical phase studies, while their mode of action is being analyzed. In this review, we summarize the research on the most promising bacterial candidates with therapeutic properties with a specific focus on diabetes.

RevDate: 2021-03-30

Li C, Pi G, F Li (2021)

The Role of Intestinal Flora in the Regulation of Bone Homeostasis.

Frontiers in cellular and infection microbiology, 11:579323.

Intestinal flora located within the intestinal tract comprises a large number of cells, which are referred to as the second gene pool of the human body and form a complex symbiotic relationship with the host. The knowledge of the complex interaction between the intestinal flora and various life activities of the host is a novel and rapidly expanding field. Recently, many studies are being conducted on the relationship between the intestinal flora and bone homeostasis and indicate that the intestinal flora can regulate bone homeostasis via the host immune, metabolic, and endocrine systems. What's more, based on several clinical and preclinical pieces of evidence, changing the composition and function of the host intestinal flora through the application of probiotics, prebiotics, and fecal microbiota transplantation is being considered to be a potential novel target for the regulation of bone homeostasis. Here, we searched relevant literature and reviewed the role of the intestinal flora in the regulation of bone homeostasis and its modulating interventions.

RevDate: 2021-03-30

Qi Z, Lyu M, Yang L, et al (2021)

A Novel and Reliable Rat Model of Autism.

Frontiers in psychiatry, 12:549810.

Background: Autism spectrum disorders (ASD) is a complex neurodevelopmental disorder that lacks an ideal animal model to recapitulate the disease state of ASD. Previous studies have reported that transplanting gut microbiota of ASD patients into pregnant mice is sufficient to promote the changes of autism-like behavior in offspring. This study aims to explore whether fecal microbiota transplantation (FMT) can be used as a new method to establish the ASD animal model. Methods: We transplanted the fecal sample extract of ASD children into pregnant rats (rFMT) repeatedly to establish an ASD rat model (oFMT) and compare it with the classical valproic acid (VPA) model (oVPA). Results: First, we reveal that oFMT shows hypoevolutism and typical behavioral characteristics of ASD, consistent with the previous study. Second, the gut microbiota of oFMT mainly consists of Firmicutes and Bacteroidetes, recapitulating the abnormal gut microbiota of ASD. In oFMT, the abundance of Lactobacillus and Collinsella increased (Lactobacillus: oFMT 60.16%, oVPA 64.13%, oCON 40.11%; Collinsella: oFMT 3.73%, oVPA 1.39%, oCON 1.28%), compared with oVPA, gut microbiota also showed high consistency. Third, the expression of 5-hydroxytryptamine (5-HT) in oFMT serum increased, γ-aminobutyric acid (GABA) and norepinephrine (NE) in oFMT serum decreased. Fourth, the gut microbiota of oFMT also has some ASD characteristic gut microbiota not found in oVPA. Fifth, pregnant rat with VPA showed significant immune activation, while those with FMT showed relatively minor immune activation. Limitations: Although the mechanism of establishing FMT autism rat model (oFMT) has not clearly defined, the data show that the model has high structural validity, and FMT model is likely to be a new and reliable potential animal model of ASD, and will have potential value in studying gut microbiota of ASD. Conclusions: The FMT autism rat model has high structural validity, and the FMT model is likely to be a new and reliable potential animal model of ASD.

RevDate: 2021-04-05

Farhadfar N, Gharaibeh RZ, Dahl WJ, et al (2021)

Gut Microbiota Dysbiosis Associated with Persistent Fatigue in Hematopoietic Cell Transplantation Survivors.

Transplantation and cellular therapy pii:S2666-6367(21)00704-1 [Epub ahead of print].

Fatigue is one of the most prevalent and distressing complications among hematopoietic stem cell transplantation (HCT) survivors, negatively affecting physical, social, and emotional domains of quality of life. Chronic systemic inflammation has been linked to alterations in nervous system activity and initiation of distressing symptoms, such as fatigue. Damage to gut mucosa due to alteration in gut microbiota (GM) composition and microbial translocation has been shown to increase systemic proinflammatory cytokines. The aim of this study was to evaluate the relationship between fatigue and GM by measuring the differences in GM composition in HCT survivors with and without persistent fatigue. This cross-sectional study included 30 adults who underwent HCT for a hematologic disease and were at least 1 year post-HCT. Patients with chronic graft-versus-host disease were excluded. Fatigue severity was assessed by the Brief Fatigue Inventory (BFI). Based on the BFI score, patients were grouped into 2 categories: 0 to 3 (without fatigue) and ≥4 (with fatigue). The V1 to V3 region of the 16S rRNA gene from fecal specimens was sequenced using the Illumina MiSeq. Sequencing reads were processed, denoised, and replicated, chimeras were filtered, amplicon sequence variants (ASVs) were generated, and taxonomy was assigned using DADA2. Beta diversity analysis through principal coordinate analysis was generated using the Bray-Curtis dissimilarity matrix, and the difference was tested using linear model with generalized least squares in R. An alpha diversity analysis was performed using Chao1. Linear discriminant analysis effect size (LEfSe) was used to find markers that differ between the 2 groups. Based on the BFI results, patients were categorized into 2 cohorts: with fatigue (n = 14) and without fatigue (n = 16). The 2 cohorts were similar in terms of demographics, disease, and transplant characteristics. Based on the GM analysis, there was a significant difference in GM composition (beta diversity) between the 2 cohorts (P = .001). Alpha diversity (richness) was also significantly lower in survivors with fatigue (P =.002). LEfSe analysis identified 46 discriminative features (P < .05; linear discriminant analysis score >2) whose relative abundance varied significantly among individuals with fatigue and those without fatigue. Ten ASVs were associated with the patients with fatigue, and 36 ASVs were associated with those without fatigue. Several ASVs enriched in survivors with fatigue included organisms such as Klebsiella and Enterococcus, which have been implicated in inflammatory bowel diseases. The ASVs enriched in the cohort without fatigue were members of the Ruminococcaceae family (Oscillospira spp) and the Lachnospiraceae family (Fusicatenibacter and Coprococcus spp), which are known to have the ability to ferment complex plant carbohydrates. These findings show an association between GM composition and fatigue and suggest a microbial contribution to clinically significant fatigue post-HCT, which may guide the development of new approaches to treating fatigue based on manipulation of the GM.

RevDate: 2021-04-02
CmpDate: 2021-04-02

Zaman A, Qazi T, Pai P, et al (2021)

Carriage rates of multidrug-resistant organisms among prospective stool donors.

The Lancet. Infectious diseases, 21(4):454-455.

RevDate: 2021-04-04

Munshi S (2021)

A depressed gut makes for a depressed brain via vagal transmission.

Brain, behavior, and immunity pii:S0889-1591(21)00119-7 [Epub ahead of print].

RevDate: 2021-04-08

Moon CM, SN Hong (2021)

Fecal Microbiota Transplantation beyond Clostridioides Difficile Infection.

Clinical endoscopy, 54(2):149-151.

With advancing analytical methods for gut microbes, many studies have been conducted, revealing that gut microbes cause various diseases, including gastrointestinal and non-gastrointestinal diseases. Accordingly, studies have been actively conducted to analyze the effects on the prevention and treatment of these diseases through changes in intestinal microbes and control of dysbiosis. Fecal microbiota transplantation (FMT) is an effort and is currently being applied to Clostridioides difficile treatment in Korea. Many studies have demonstrated the application of FMT in inflammatory bowel disease, irritable bowel syndrome, non-alcoholic fatty liver disease, metabolic syndrome, obesity, and diabetes. With further studies and accumulation of evidence, FMT could help treat presently untreatable diseases in clinical practice.

RevDate: 2021-04-08

Gweon TG, SY Na (2021)

Next Generation Fecal Microbiota Transplantation.

Clinical endoscopy, 54(2):152-156.

Fecal microbiota transplantation (FMT) is considered as an effective treatment for Clostridioides difficile infection. However, the precise mechanism of FMT is yet to be determined. Human stool consists of the gut microbiota, bacterial debris, and metabolic products. Of these, the intestinal microbiota is the most important factor that exerts therapeutic efficacy in FMT. Fresh donor stool, blended with normal saline, has been employed for traditional FMT. Nevertheless, stool processing is a major impediment in FMT. Frozen stool and capsule formulations have similar efficacy to that of fresh stool. In addition, several novel stool products have been identified. A stool bank that provides stool products with pre-screened donor stool has been established to help physicians and thereby facilitate FMT. Recent next-generation sequencing techniques have been key in facilitating the detailed analysis of the microbiota and gut environment of individual donors and recipients.

RevDate: 2021-03-24

Cheng F, Huang Z, Wei W, et al (2021)

Fecal microbiota transplantation for Crohn's disease: a systematic review and meta-analysis.

Techniques in coloproctology [Epub ahead of print].

BACKGROUND: Crohn's disease (CD) is a chronic idiopathic inflammatory intestinal disorder associated with fecal dysbiosis. Fecal microbiota transplantation (FMT) is an emerging treatment approach for CD. But its efficacy and safety remain controversial. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of FMT in CD patients.

METHODS: Electronic databases were searched for studies that reported efficacy and/or safety of FMT for CD. Clinical remission was established as the primary outcome. Secondary outcome was clinical response. Odds ratios with 95% confidence intervals (CIs) were reported.

RESULTS: In all, 12 trials were included in our study. Pooled analysis showed that 0.62 (95% CI 0.48, 0.81) of CD patients achieved clinical remission and 0.79 (95% CI 0.71, 0.89) of CD patients achieved clinical response post-FMT. Sub-analyses suggested the rate of clinical remission with fresh stool FMT was higher than with frozen stool FMT (73% vs 43%; p < 0.05). Most adverse events were minor and self-resolving and no major FMT-related adverse event has been reported so far.

CONCLUSIONS: The evidence showed that FMT is an effective and safe therapy for CD. FMT may be successful because it increases the overall diversity of enteric microbiome. Additional randomized controlled studies are needed.

RevDate: 2021-04-17

Wang W, Zhai D, Bai Y, et al (2021)

Loss of QKI in macrophage aggravates inflammatory bowel disease through amplified ROS signaling and microbiota disproportion.

Cell death discovery, 7(1):58.

Inflammatory bowel disease (IBD) is a refractory chronic inflammatory illness of the gastrointestinal (GI) tract. Macrophage exerts an important role in IBD development. QKI, as an RNA binding protein, was related with inflammatory responses in bacterial infections by regulating the polarization of macrophages. Therefore, we suspected that QKI-regulated macrophages have the potential to play a certain role in IBD and the underlying mechanism. Our results demonstrated that the mice with macrophage-specific deletion of QKI induced with dextran sodium sulfate (DSS) are more susceptible to IBD development, exhibited a severe leaky gut barrier phenotype and higher intense oxidative stress, which are rescued by treating with butylated hydroxyanisole (BHA), an agonist of NRF2. Mechanically, we observed that Keap1 mRNA in the nucleus was exported to the cytoplasm after LPS stimuli in parallel with QKI reductions, and the removal of QKI by shRNA facilitated Keap1 mRNA nuclear exporting and expression in cytoplasm, consequently NRF2 activation in nucleus was weakened, and led to the impaired antioxidant abilities. In addition, mice models of fecal microbiota transplant (FMT) and the co-culturing of mice epithelia cells with feces derived from the DSS-treated QKI-deficit mice revealed consistently aggravated colitis along with a severe oxidative stress; 16S sequencing analysis substantiated the altered compositions of commensal bacteria too. Overall, the current study represents the first effort to explore the anti-oxidant role of QKI in the intestinal macrophage via post-transcriptional regulation of Keap1 mRNA localization and the relevant NRF2 antioxidant signaling, and the disproportional changes in the microbiota were attributable to the mediation of pathogenic damage in the IBD development of QKI-deficit mice.

RevDate: 2021-03-27

Santiago M, SW Olesen (2021)

16S rRNA sequencing of samples from universal stool bank donors.

BMC research notes, 14(1):108.

OBJECTIVES: Universal stool banks provide stool to physicians for use in treating recurrent Clostridioides difficile infection via fecal microbiota transplantation. Stool donors providing the material are rigorously screened for diseases and disorders with a potential microbiome etiology, and they are likely healthier than the controls in most microbiome datasets. 16S rRNA sequencing was performed on samples from a selection of stool donors at a large stool bank, OpenBiome, to characterize their gut microbial community and to compare samples across different timepoints and sequencing runs.

DATA DESCRIPTION: 16S rRNA sequencing was performed on 200 samples derived from 170 unique stool donations from 86 unique donors. Samples were sequenced on 11 different sequencing runs. We are making this data available because rigorously screened, likely very healthy stool donors may be useful for characterizing and understanding microbial community differences across different populations and will help shed light into the how the microbiome community promotes health and disease.

RevDate: 2021-03-23

Zhang Y, Zhang S, Li B, et al (2021)

Gut microbiota dysbiosis promotes age-related atrial fibrillation by lipopolysaccharide and glucose-induced activation of NLRP3-inflammasome.

Cardiovascular research pii:6184135 [Epub ahead of print].

AIMS: Aging is the most significant contributor to the increasing prevalence of atrial fibrillation (AF). The gut microbiota dysbiosis is involved in age-related diseases. However, whether the aged-associated dysbiosis contributes to age-related AF is still unknown. Direct demonstration that the aged gut microbiota is sufficient to transmit the enhanced AF susceptibility in a young host via microbiota-intestinal barrier-atria axis has not yet been reported. This study aimed to determine whether gut microbiota dysbiosis affects age-related AF.

METHODS AND RESULTS: Herein, by using a fecal microbiota transplantation (FMT) rat model, we demonstrated that the high AF susceptibility of aged rats could be transmitted to a young host. Specially, we found the dramatically increased levels of circulating lipopolysaccharide (LPS) and glucose led to the up-regulated expression of NLR family pyrin domain containing 3 (NLRP3)-inflammasome, promoting the development of AF which depended on the enhanced atrial fibrosis in recipient host. Inhibition of inflammasome by a potent and selective inhibitor of the NLRP3 inflammasome, MCC950, resulted in a lower atrial fibrosis and AF susceptibility. Then we conducted cross-sectional clinical studies to explore the effect of aging on the altering trends with glucose levels and circulating LPS among clinical individuals in two China hospitals. We found that both of serum LPS and glucose levels were progressively increased in elderly patients as compared with those young. Furthermore, the aging phenotype of circulating LPS and glucose levels, intestinal structure and atrial NLRP3-inflammasome of rats were also confirmed in clinical AF patients. Finally, aged rats colonized with youthful microbiota restored intestinal structure and atrial NLRP3-inflammasome activity, which suppressed the development of aged-related AF.

CONCLUSIONS: Collectively, these studies described a novel causal role of aberrant gut microbiota in the pathogenesis of age-related AF, which indicates that the microbiota-intestinal barrier-atrial NLRP3 inflammasome axis may be a rational molecular target for the treatment of aged-related arrhythmia disease.

TRANSLATIONAL PERSPECTIVE: The current study demonstrates that aged-associated microbiota dysbiosis promotes AF in part through a microbiota-gut-atria axis. Increased AF susceptibility due to enhanced atrial NLRP3-inflammasome activity by LPS and high glucose was found in an aged FMT rat model, and also confirmed within elderly clinical individuals. In a long-term FMT rat study, the AF susceptibility was ameliorated by treatment with youthful microbiota. The present findings can further increase our understanding of aged-related AF and address a promising therapeutic strategy that involves modulation of gut microbiota composition.

RevDate: 2021-04-01

Zhang SL, Mao YQ, Zhang ZY, et al (2021)

Pectin supplement significantly enhanced the anti-PD-1 efficacy in tumor-bearing mice humanized with gut microbiota from patients with colorectal cancer.

Theranostics, 11(9):4155-4170.

Background: Anti-PD-1-based immunotherapy has emerged as a promising therapy for several cancers. However, it only benefits a small subset of colorectal cancer (CRC) patients. Mounting data supports the pivotal role of gut microbiota in shaping immune system. Pectin, a widely consumed soluble fiber, has been reported to ameliorate the imbalance of gut microbiota. Therefore, we aimed to explore the effect and the underlying mechanisms of pectin in improving anti-PD-1 mAb efficacy. Methods: The C57BL/6 mice were treated with a broad-spectrum antibiotic (ATB) cocktail to depleted endogenous gut microbiota and subsequently humanized with feces from healthy controls or newly diagnosed CRC patients. The antitumor efficacies of anti-PD-1 mAb combined with or without pectin were assessed using these mice. Flow cytometry and immunohistochemistry (IHC) were conducted to investigate the tumor immune microenvironment after treatment. The gut microbiota profiles and short-chain fatty acids (SCFAs) levels were determined by 16S ribosomal RNA (16S rRNA) gene sequencing and gas chromatography-mass spectrometry (GC-MS), respectively. The effect of gut microbiota on anti-PD-1 mAb efficacy after pectin supplement was further tested by fecal microbiota transplantation (FMT). Results: The anti-PD-1 mAb efficacy was largely impaired in the mice humanized with feces from newly diagnosed CRC patients compared to those from healthy controls. However, pectin significantly enhanced the anti-PD-1 mAb efficacy in the tumor-bearing mice humanized with CRC patient gut microbiota. Flow cytometry and IHC analysis revealed increased T cell infiltration and activation in the tumor microenvironment of mice treated with anti-PD-1 mAb plus pectin. In vivo depletion of CD8+ T cells diminished the anti-tumor effect of anti-PD-1 mAb combined with pectin. 16S rRNA gene sequencing showed that pectin significantly increased gut microbial diversity and beneficially regulated microbial composition. In addition, we identified unique bacterial modules that were significantly enriched in the anti-PD-1 mAb + pectin group, which composed of butyrate-producing bacteria indicative of good response to immunotherapy. Meanwhile, GC-MS showed that pectin altered the level of SCFA butyrate. Furthermore, butyrate, a main product of dietary fiber in gut microbial fermentation, was found to be sufficient to promote T cells infiltration and thus enhance the efficacy of anti-PD-1 mAb. In addition, FMT demonstrated the effects of pectin were dependent on gut microbiota. Importantly, the beneficial effects of pectin were confirmed in the mice humanized with gut microbiota from patient with resistance to anti-PD-1 mAb. Conclusion: Pectin facilitated the anti-PD-1 mAb efficacy in CRC via regulating the T cell infiltration in the tumor microenvironment, which was potentially mediated by the metabolite butyrate.

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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.

Speaker

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.

Facilitator

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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