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14 Oct 2019 at 01:32
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Bibliography on: Fecal Transplantation


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RJR: Recommended Bibliography 14 Oct 2019 at 01:32 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®)

RevDate: 2019-10-11

Madar PC, Petre O, Baban A, et al (2019)

Medical students' perception on fecal microbiota transplantation.

BMC medical education, 19(1):368 pii:10.1186/s12909-019-1804-7.

BACKGROUND: Fecal microbiota transplantation (FMT) has become an emergent method in the therapy of several intestinal diseases, mainly in Clostridium difficile recurrence. The training of FMT in medical schools is at its beginning and in countries where FMT is only occasionally carried out, it is important to know the perception of medical students on FMT.

METHODS: We undertook a survey of 3rd year medical students not exposed to official academic information on FMT in order to find out their knowledge, beliefs and attitude toward FMT. A number of 80 students were asked to fill a dedicated online questionnaire.

RESULTS: 52 out of 80 third year medical students anonymously filled the questionnaire (65% response rate). 34% of respondents reported to have at least a medium level of knowledge regarding FMT. The top indication for FMT identified by 76.9% was C. difficile infection; however, 60% believed FMT to be a promising therapy for a high number of conditions and while almost all respondents (98.1%) would recommend it, 88.4% would explore other options first. Colonoscopy was considered the optimal method of delivery by 42.3%. Only 39% of participants believed that patients would accept FMT, however 71% considered that a more socially acceptable name for the procedure and anonymous donors would increase acceptance rate. The risk of transmitting a disease undetected by donor stool screening procedures to the recipient was the most worrying side effect considered by 75% of respondents. 54% believed that more research is required for FMT to enter clinical practice and 55.7% of respondents would enroll patients in controlled clinical trials.

CONCLUSIONS: Medical students not exposed to educational information on FMT seem to be somewhat well informed about this method and would recommend it to their patients. Students, however, need to know more on the indications of FMT.

RevDate: 2019-10-11
CmpDate: 2019-10-11

Paramsothy S, NO Kaakoush (2019)


Gastroenterology, 157(4):1165-1166.

RevDate: 2019-10-11
CmpDate: 2019-10-11

Kellermayer R (2019)

Roseburia Species: Prime Candidates for Microbial Therapeutics in Inflammatory Bowel Disease.

Gastroenterology, 157(4):1164-1165.

RevDate: 2019-10-10

Duvallet C, Zellmer C, Panchal P, et al (2019)

Framework for rational donor selection in fecal microbiota transplant clinical trials.

PloS one, 14(10):e0222881 pii:PONE-D-19-13813.

Early clinical successes are driving enthusiasm for fecal microbiota transplantation (FMT), the transfer of healthy gut bacteria through whole stool, as emerging research is linking the microbiome to many different diseases. However, preliminary trials have yielded mixed results and suggest that heterogeneity in donor stool may play a role in patient response. Thus, clinical trials may fail because an ineffective donor was chosen rather than because FMT is not appropriate for the indication. Here, we describe a conceptual framework to guide rational donor selection to increase the likelihood that FMT clinical trials will succeed. We argue that the mechanism by which the microbiome is hypothesized to be associated with a given indication should inform how healthy donors are selected for FMT trials, categorizing these mechanisms into four disease models and presenting associated donor selection strategies. We next walk through examples based on previously published FMT trials and ongoing investigations to illustrate how donor selection might occur in practice. Finally, we show that typical FMT trials are not powered to discover individual taxa mediating patient responses, suggesting that clinicians should develop targeted hypotheses for retrospective analyses and design their clinical trials accordingly. Moving forward, developing and applying novel clinical trial design methodologies like rational donor selection will be necessary to ensure that FMT successfully translates into clinical impact.

RevDate: 2019-10-10

Shah H, P Zezos (2019)

Pouchitis: diagnosis and management.

Current opinion in gastroenterology [Epub ahead of print].

PURPOSE OF REVIEW: Pouchitis is the most common complication in patients who undergo ileal pouch-anal anastomosis (IPAA), occurring more frequently in patients with ulcerative colitis. Pouchitis - the inflammation of the pouch - can be due to idiopathic or secondary causes. Chronic antibiotic-dependent pouchitis (CADP) and chronic antibiotic-resistant pouchitis (CARP) are the most difficult forms of chronic idiopathic pouchitis to treat. Crohn's disease of the pouch may develop de novo in ulcerative colitis patients following colectomy with IPAA. It carries a high risk for pouch failure, and its diagnosis and management are challenging. The purpose of this review is to illustrate the present trends in the diagnosis and treatment of idiopathic pouchitis and Crohn's disease of the pouch.

RECENT FINDINGS: The use of the newer biologic agents, vedolizumab and ustekinumab, has shown promising results in patients with CADP, CARP, and Crohn's disease of the pouch. Fecal microbiota transplantation has also been reported to have encouraging preliminary results in small studies and case series for the treatment of chronic pouchitis.

SUMMARY: Promising new treatments are emerging for difficult-to-treat forms of pouchitis. Larger prospective and head-to-head comparative studies among the various treatments are needed to evaluate the efficacy and safety of these agents across the pouchitis subgroups, and to identify predictors of response.

RevDate: 2019-10-10
CmpDate: 2019-10-10

Frye RE (2018)

Social Skills Deficits in Autism Spectrum Disorder: Potential Biological Origins and Progress in Developing Therapeutic Agents.

CNS drugs, 32(8):713-734.

Autism spectrum disorder is defined by two core symptoms: a deficit in social communication and the presence of repetitive behaviors and/or restricted interests. Currently, there is no US Food and Drug Administration-approved drug for these core symptoms. This article reviews the biological origins of the social function deficit associated with autism spectrum disorder and the drug therapies with the potential to treat this deficit. A review of the history of autism demonstrates that a deficit in social interaction has been the defining feature of the concept of autism from its conception. Abnormalities identified in early social skill development and an overview of the pathophysiology abnormalities associated with autism spectrum disorder are discussed as are the abnormalities in brain circuits associated with the social function deficit. Previous and ongoing clinical trials examining agents that have the potential to improve social deficits associated with autism spectrum disorder are discussed in detail. This discussion reveals that agents such as oxytocin and propranolol are particularly promising and undergoing active investigation, while other agents such as vasopressin agonists and antagonists are being activity investigated but have limited published evidence at this time. In addition, agents such as bumetanide and manipulation of the enteric microbiome using microbiota transfer therapy appear to have promising effects on core autism spectrum disorder symptoms including social function. Other pertinent issues associated with developing treatments in autism spectrum disorder, such as disease heterogeneity, high placebo response rates, trial design, and the most appropriate way of assessing effects on social skills (outcome measures), are also discussed.

RevDate: 2019-10-09

Mashaqi S, D Gozal (2019)

Obstructive Sleep Apnea and Systemic Hypertension: Gut Dysbiosis as the Mediator?.

Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 15(10):1517-1527.

INTRODUCTION: Obstructive sleep apnea (OSA) and systemic hypertension (SH) are common and interrelated diseases. It is estimated that approximately 75% of treatment-resistant hypertension cases have an underlying OSA. Exploration of the gut microbiome is a new advance in medicine that has been linked to many comorbid illnesses, including SH and OSA. Here, we will review the literature in SH and gut dysbiosis, OSA and gut dysbiosis, and whether gut dysbiosis is common in both conditions.

METHODS: We reviewed the National Center for Biotechnology Information database, including PubMed and PubMed Central. We identified a total of 230 articles. The literature search was conducted using the phrase "obstructive sleep apnea and gut dysbiosis." Only original research articles were included. This yielded a total of 12 articles.

RESULTS: Most of the research conducted in this field was on animal models, and almost all trials confirmed that intermittent hypoxia models resulted in gut dysbiosis. Gut dysbiosis, however, can cause a state of low-grade inflammation through damage to the gut wall barrier resulting in "leaky gut." Neuroinflammation is a hallmark of the pathophysiology of OSA-induced SH.

CONCLUSIONS: Gut dysbiosis seems to be an important factor in the pathophysiology of OSA-induced hypertension. Reversing gut dysbiosis at an early stage through prebiotics and probiotics and fecal microbiota transplantation combined with positive airway pressure therapy may open new horizons of treatment to prevent SH. More studies are needed in humans to elicit the effect of positive airway pressure therapy on gut dysbiosis.

RevDate: 2019-10-09

Li L, Li X, Zhong W, et al (2019)

Gut microbiota from colorectal cancer patients enhances the progression of intestinal adenoma in Apcmin/+ mice.

EBioMedicine pii:S2352-3964(19)30625-5 [Epub ahead of print].

BACKGROUND: Accumulating evidence points to a close relationship between gut dysbiosis and colorectal cancer (CRC). As >90% of CRC develop from adenoma, we aimed to investigate the crucial role of imbalanced gut microbiota on the progression of intestinal adenoma.

METHODS: The Apcmin/+ mice gavage with phosphate-buffered saline (PBS), feces from healthy controls or CRC patients after antibiotic cocktails. The intestinal tissues were isolated for histopathology, western blotting, and RNA-seq. The microbiota of feces and short-chain fatty acids (SCFAs) were analysed by 16S rDNA Amplicon Sequencing and gas chromatography.

FINDINGS: The Apcmin/+mice gavaged by feces from CRC patients had more intestinal tumours compared with those fed with feces from healthy controls or PBS. Administration of feces from CRC patients increased tumour proliferation and decreased apoptosis in tumour cells, accompanied by impairment of gut barrier function and up-regulation the pro-inflammatory cytokines profile. The up-regulated the expression of β-catenin and cyclinD1 further indicating the activation of Wnt signalling pathway. The abundance of pathogenic bacteria was increased after FMT, while producing SCFAs bacteria and SCFAs production were decreased.

INTERPRETATION: Gut microbiota of CRC patients disrupted intestinal barrier, induced low-grade inflammation and dysbiosis. The altered gut microbiota enhanced the progression of intestinal adenomas in Apcmin/+mice, suggesting that a new strategy to target gut microbiota against CRC could be noted. FUND: The study was supported by the National Natural Science Foundation of China, Tianjin Research Programme of Application Foundation and Advanced Technology of China, and China Postdoctoral Science Foundation.

RevDate: 2019-10-09

Benno P, Norin E, Midtvedt T, et al (2019)

Therapeutic potential of an anaerobic cultured human intestinal microbiota, ACHIM, for treatment of IBS.

Best practice & research. Clinical gastroenterology, 40-41:101607.

By administering an anaerobic cultivated human intestinal microbiota (ACHIM) via upper gastrointestinal route using endoscopy we aimed to rectify intestinal dysbiosis and simultaneously achieve a treatment response in IBS patients. The study population fulfilled the Rome III IBS criteria and comprised 50 patients. During 10 days, patients recorded the irritable bowel syndrome symptom severity scale (IBS-SSS) along with the Bristol stool scale and number of stools/day. The enrolled patients were categorized as follows: 37 with diarrhea, 5 with constipation and 8 with mixed symptoms. The treatment response showed reduction in a majority of patients, 32 of which with 50-point reduction of IBS-SSS and 21 with a 100-point IBS-SSS reduction. The percentage improvement was 36 (23-49) and 28 (18-38) for women and men respectively. Short-chain fatty acids were not changed. We consider fecal microbiota transplantation in the form of ACHIM as an option for the future therapeutic armamentarium in IBS. REGISTERED TRIAL: www.clinicaltrials.gov NCT02857257.

RevDate: 2019-10-09

Yin G, Li JF, Sun YF, et al (2019)

[Fecal microbiota transplantation as a novel therapy for severe psoriasis].

Zhonghua nei ke za zhi, 58(10):782-785.

To explore the therapeutic effect of fecal microbiota transplantation (FMT) for severe psoriasis. A patient, male, 36 years old, diagnosed as severe plaque psoriasis for 10 years and irritable bowel syndrome (IBS) for 15 years, was administrated twice FMT via both upper endoscopy and colonoscopy with a 5-week interval. The following items were used to evaluate responses: body surface area (BSA), psoriasis area and severity index (PASI), dermatology life quality index (DLQI), histological examination, intestinal symptoms, adverse reactions and serum level of tumor necrosis factor (TNF)-α. After second FMT treatment for 5 weeks, aforementioned items were improved greatly compared with those before treatment. Moreover, IBS was completely relieved and no adverse reactions were observed during the treatment and follow-up. In conclusion, FMT could be a novel therapy for psoriasis. Further clinical trials are needed to provide solid evidences.

RevDate: 2019-10-07
CmpDate: 2019-10-07

Majid A, M Jamali (2018)

Faecal microbial transplant: Therapy of the past, magic pill of the present?.

JPMA. The Journal of the Pakistan Medical Association, 68(4):691.

RevDate: 2019-10-06

Aggeletopoulou I, Konstantakis C, Assimakopoulos SF, et al (2019)

The role of the gut microbiota in the treatment of inflammatory bowel diseases.

Microbial pathogenesis pii:S0882-4010(19)30957-X [Epub ahead of print].

The human intestinal microbiota coevolves with its host through a symbiotic relationship and exerts great influence on substantial functions including aspects of physiology, metabolism, nutrition and regulation of immune responses leading to physiological homeostasis. Over the last years, several studies have been conducted toward the assessment of the host-gut microbiota interaction, aiming to elucidate the mechanisms underlying the pathogenesis of several diseases. A defect on the microbiota-host crosstalk and the concomitant dysregulation of immune responses combined with genetic and environmental factors have been implicated in the pathogenesis of inflammatory bowel diseases (IBD). To this end, novel therapeutic options based on the gut microbiota modulation have been an area of extensive research interest. In this review we present the recent findings on the association of dysbiosis with IBD pathogenesis, we focus on the role of gut microbiota on the treatment of IBD and discuss the novel and currently available therapeutic strategies in manipulating the composition and function of gut microbiota in IBD patients. Applicable and emerging microbiota treatment modalities, such as the use of antibiotics, prebiotics, probiotics, postbiotics, synbiotics and fecal microbiota transplantation (FMT) constitute promising therapeutic options. However, the therapeutic potential of the aforementioned approaches is a topic of investigation and further studies are needed to elucidate their position in the present treatment algorithms of IBD.

RevDate: 2019-10-06

Song M, Chan AT, J Sun (2019)

Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer.

Gastroenterology pii:S0016-5085(19)41369-3 [Epub ahead of print].

Researchers have discovered associations between elements of the intestinal microbiome (including specific microbes, signaling pathways, and microbiota-related metabolites) and risk of colorectal cancer (CRC). However, it is unclear whether changes in the intestinal microbiome contribute to development of sporadic CRC or result from it. Changes in the intestinal microbiome can mediate or modify the effects of environmental factors on risk of CRC. Factors that affect risk of CRC also affect the intestinal microbiome, including overweight and obesity; physical activity; and dietary intake of fiber, whole grains, and red and processed meat. These factors alter microbiome structure and function, along with the metabolic and immune pathways that mediate CRC development. We review epidemiologic and laboratory evidence for the influence of the microbiome, diet, and environmental factors on CRC incidence and outcomes. Based on these data, features of the intestinal microbiome might be used for CRC screening and modified for chemoprevention and treatment. Integrated prospective studies are urgently needed to investigate these strategies.

RevDate: 2019-10-04

Dougé A, Bay JO, Ravinet A, et al (2019)

[Intestinal microbiota and allogeneic stem cell transplantation].

Bulletin du cancer pii:S0007-4551(19)30330-3 [Epub ahead of print].

Allogeneic hematopoïetic stem cell transplantation is one of the most efficient curative treatment for acute leukemia. But it is also a heavy process with an important risk of complications, particularly infection and graft versus host disease. Increasing data in literature show that an alteration of the intestinal microbiota of allogeneic stem cell recipients is associated with these complications. Indeed, treatments used during conditioning regimen lead to an impaired microbiota, which cannot fulfill its protective functions anymore. To limit this microbiota impairment, we could restore a healthy microbiota by a fecal microbiota transplantation, which has already shown its efficiency in the treatment of Clostridium difficile infection. The aim of this review is to describe the intestinal microbiota, the link between microbiota and complications of allogeneic stem cells transplantation, and the recent published data on fecal microbiota transplantation in this field.

RevDate: 2019-10-03

Drewes JL, Corona A, Sanchez U, et al (2019)

Transmission and clearance of potential procarcinogenic bacteria during fecal microbiota transplantation for recurrent Clostridioides difficile.

JCI insight, 4(19): pii:130848.

BACKGROUNDFecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infection (rCDI) in adults and children, but donor stool samples are currently screened for only a limited number of potential pathogens. We sought to determine whether putative procarcinogenic bacteria (enterotoxigenic Bacteroides fragilis, Fusobacterium nucleatum, and Escherichia coli harboring the colibactin toxin) could be durably transmitted from donors to patients during FMT.METHODSStool samples were collected from 11 pediatric rCDI patients and their respective FMT donors prior to FMT as well as from the patients at 2-10 weeks, 10-20 weeks, and 6 months after FMT. Bacterial virulence factors in stool DNA extracts and stool cultures were measured by quantitative PCR: Bacteroides fragilis toxin (bft), Fusobacterium adhesin A (fadA), and Escherichia coli colibactin (clbB).RESULTSFour of 11 patients demonstrated sustained acquisition of a procarcinogenic bacteria. Whole genome sequencing was performed on colony isolates from one of these donor/recipient pairs and demonstrated that clbB+ E. coli strains present in the recipient after FMT were identical to a strain present in the donor, confirming strain transmission. Conversely, 2 patients exhibited clearance of procarcinogenic bacteria following FMT from a negative donor.CONCLUSIONBoth durable transmission and clearance of procarcinogenic bacteria occurred following FMT, suggesting that additional studies on appropriate screening measures for FMT donors and the long-term consequences and/or benefits of FMT are warranted.FUNDINGCrohn's & Colitis Foundation, the Bloomberg~Kimmel Institute for Cancer Immunotherapy at Johns Hopkins University School of Medicine, the National Cancer Institute, and the Canadian Institutes of Health Research.

RevDate: 2019-10-01

Genton L, Mareschal J, Charretier Y, et al (2019)

Targeting the Gut Microbiota to Treat Cachexia.

Frontiers in cellular and infection microbiology, 9:305.

Cachexia occurs in many chronic diseases and is associated with increased morbidity and mortality. It is treated by nutritional support but often with limited effectiveness, leading to the search of other therapeutic strategies. The modulation of gut microbiota, whether through pro-, pre-, syn- or antibiotics or fecal transplantation, is attracting ever-growing interest in the field of obesity, but could also be an interesting and innovative alternative for treating cachexia. This article reviews the evidence linking the features of malnutrition, as defined by the Global Leadership Initiative on Malnutrition [low body mass index (BMI), unintentional body weight loss, low muscle mass, low appetite, and systemic inflammation] and the gut microbiota in human adults with cachexia-associated diseases, and shows the limitations of the present research in that field with suggestions for future directions.

RevDate: 2019-10-01

Zhou H, Tai J, Xu H, et al (2019)

Xanthoceraside Could Ameliorate Alzheimer's Disease Symptoms of Rats by Affecting the Gut Microbiota Composition and Modulating the Endogenous Metabolite Levels.

Frontiers in pharmacology, 10:1035.

Xanthoceraside (XAN) is a natural-derived compound with anti-Alzheimer activity from the husks of Xanthoceras sorbifolia. Although its therapeutic effect had been confirmed in previous studies, the mechanism was still unclear due to its poor solubility and low permeability. In this study, the pharmacological effect of XAN on Alzheimer's disease (AD) was confirmed by behavior experiments and H&E staining observation. Fecal microbiota transplantation (FMT) experiment also replicated the therapeutic effects, which indicates the potential targets of XAN on gut microbiota. The sequencing of 16S rRNA genes in fecal samples demonstrated that XAN reversed gut microbiota dysbiosis in AD animals. XAN could change the relative abundances of several phyla and genus of bacterial, particularly the ratio of Firmicutes/Bacteroidetes. Among them, Clostridium IV, Desulfovibrio, Corynebacterium, and Enterorhabdus had been reported to be involved in the pathologic developments of AD and other central nervous system disease. In metabolomics study, a series of host endogenous metabolites were detected, including amino acids, lysophosphatidylcholine, dihydrosphingosine, phytosphingosine, inosine, and hypoxanthine, which were all closely associated with the development of AD. Combined with the Spearman's correlation analysis, it was confirmed that the increases of five bacterial strains and decreases of six bacterial strains were closely correlated with the increases of nine host metabolites and the decreases of another five host metabolites. Therefore, XAN can modulate the structure of gut microbiota in AD rats; the changes of gut microbiota were significantly correlated with endogenous metabolites, and symptom of AD was ultimately alleviated. Our findings suggest that XAN may be a potential therapeutic drug for AD, and the gut microbiota may be potential targeting territory of XAN via microbiome-gut-brain pathway.

RevDate: 2019-10-01

Liu Y, Chen K, Li F, et al (2019)

Probiotic LGG prevents liver fibrosis through inhibiting hepatic bile acid synthesis and enhancing bile acid excretion in mice.

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

Cholestatic liver disease is characterized by gut dysbiosis and excessive toxic hepatic bile acids (BAs). Modification of gut microbiota and repression of BA synthesis are potential strategies for the treatment of cholestatic liver disease. The purpose of this study was to examine the effects and to understand the mechanisms of the probiotic, Lactobacillus rhamnosus GG (LGG), on hepatic bile acid synthesis, liver injury and fibrosis in bile-duct ligation (BDL) and Mdr2-/- mice. Global and intestinal specific FXR inhibitors were used to dissect the role of FXR. LGG treatment significantly attenuated liver inflammation, injury and fibrosis with a significant reduction of hepatic BAs in BDL mice. Hepatic concentration of T-βMCA, an FXR antagonist, was markedly increased in BDL mice and reduced in LGG-treated mice, while chenodeoxycholic acid (CDCA), an FXR agonist, was decreased in BDL mice and normalized in LGG-treated mice. LGG treatment significantly increased the expression of serum and ileum FGF15 and subsequently reduced hepatic CYP7A1 and BA synthesis in BDL and Mdr2-/- mice. At the molecular level, these changes were reversed by global and intestinal specific FXR inhibitors in BDL mice. In addition, LGG treatment altered gut microbiota, which was associated with increased BA de-conjugation and increased fecal and urine BA excretion both in BDL and Mdr2-/- mice. In vitro studies showed that LGG suppressed the inhibitory effect of T-βMCA on FXR and FGF19 expression in Caco-2 cells. Conclusion: LGG supplementation decreases hepatic BA by increasing intestinal FXR/FGF15 signaling pathway-mediated suppression of BA de novo synthesis and enhances BA excretion, which prevents excessive BA-induced liver injury and fibrosis in mice.

RevDate: 2019-10-01

Elangovan A, Allegretti JR, M Fischer (2019)

Microbiota modulation-based therapy for Luminal GI disorders: Current Applications of Probiotics and Fecal Microbiota Transplantation.

Expert opinion on biological therapy [Epub ahead of print].

INTRODUCTION: Alteration in the intestinal microbiota also termed as intestinal dysbiosis has been demonstrated in numerous gastrointestinal disorders linked to aberrant immune processes, acquisition of pathogenic organisms and often administration of antibiotics. Restoration of microbiota through probiotics and fecal microbiota transplantation (FMT) has gained tremendous popularity among researchers in the prevention and treatment of gastrointestinal diseases. Areas covered: In this review, studies testing the safety and efficacy of probiotics and FMT for the treatment of various infectious and inflammatory luminal gastrointestinal diseases are reviewed. Randomized control studies are given priority while important uncontrolled studies are also highlighted. Expert Opinion: Probiotics have demonstrated efficacy in the prevention of antibiotic-associated diarrhea and in the eradication of Helicobacter pylori infection. Their utility in the primary and secondary prevention of Clostridioides difficile infection is debatable. The future of medicine should bring forth a personalized approach to probiotic use. FMT has revolutionized the treatment of recurrent CDI as well as severe and fulminant CDI. At the same time, it has galvanized gut microbiota research in the last decade. While FMT in ulcerative colitis appears promising, further studies on the durability and long-term safety are needed before it can be recommended in clinical practice.

RevDate: 2019-10-01

Ma J, Li J, Qian M, et al (2019)

The comprehensive pathophysiological changes in a novel rat model of postinflammatory visceral hypersensitivity.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology [Epub ahead of print].

So far, a comprehensive animal model that can mimic both the central and peripheral pathophysiological changes of irritable bowel syndrome (IBS) is lacking. Here, we developed a novel IBS rat model combining trinitro-benzene-sulfonic acid (TNBS) and chronic unpredictable mild stress (CUMS) (designated as TC-IBS) and compared it with the TNBS-induced and CUMS-induced models. TC-IBS showed a pronounced depression phenotype with increased corticotropin-releasing hormone receptor (CRHR)1 and CRHR2 expression at the frontal cortex and increased serum ACTH concentration. Visceral hypersensitivity (VH), as evidenced by colorectal distention (CRD) test, was highest in TC-IBS, accompanied by increased serum 5-hydroxytryptamine (5-HT) level and colonic 5-HT receptor 3A (5-HT3AR)/5-HT receptor 2B expression, impaired tight junction protein expression including occludin, zonula occludens-1, and phosphorylated myosin light chain. Palonosetron, a second generation of 5-HT3AR antagonist, alleviated VH significantly in TC-IBS. 16S rRNA sequencing showed that TNBS plus CUMS induced a significant disturbance of the gut microbiota. Cytokine profile analysis of TC-IBS model indicated an innate immune activation both in serum and colonic mucosa. Further, fecal microbiota transplantation improved VH and some pathophysiological changes in TC-IBS. In summary, we established a postinflammatory IBS model covering multifactorial pathophysiological changes, which may help to develop therapies that target specific IBS subtype.-Ma, J., Li, J., Qian, M., He, N., Cao, Y., Liu, Y., Wu, K., He, S. The comprehensive pathophysiological changes in a novel rat model of postinflammatory visceral hypersensitivity.

RevDate: 2019-10-02
CmpDate: 2019-10-02

Zaheer M, Wang C, Bian F, et al (2018)

Protective role of commensal bacteria in Sjögren Syndrome.

Journal of autoimmunity, 93:45-56.

CD25 knock-out (CD25KO) mice spontaneously develop Sjögren Syndrome (SS)-like inflammation. We investigated the role of commensal bacteria by comparing CD25KO mice housed in conventional or germ-free conditions. Germ-free CD25KO mice have greater corneal barrier dysfunction, lower goblet cell density, increased total lymphocytic infiltration score, increased expression of IFN-γ, IL-12 and higher a frequency of CD4+IFN-γ+ cells than conventional mice. CD4+ T cells isolated from female germ-free CD25KO mice adoptively transferred to naive immunodeficient RAG1KO recipients caused more severe Sjögren-like disease than CD4+ T cells transferred from conventional CD25KO mice. Fecal transplant in germ-free CD25KO mice reversed the spontaneous dry eye phenotype and decreased the generation of pathogenic CD4+IFN-γ+ cells. Our studies indicate that lack of commensal bacteria accelerates the onset and severity of dacryoadenitis and generates autoreactive CD4+T cells with greater pathogenicity in the CD25KO model, suggesting that the commensal bacteria or their metabolites products have immunoregulatory properties that protect exocrine glands in the CD25KO SS model.

RevDate: 2019-09-27

Zhang Z, Mocanu V, Cai C, et al (2019)

Impact of Fecal Microbiota Transplantation on Obesity and Metabolic Syndrome-A Systematic Review.

Nutrients, 11(10): pii:nu11102291.

Fecal microbiota transplantation (FMT) is a gut microbial-modulation strategy that has been investigated for the treatment of a variety of human diseases, including obesity-associated metabolic disorders. This study appraises current literature and provides an overview of the effectiveness and limitations of FMT as a potential therapeutic strategy for obesity and metabolic syndrome (MS). Five electronic databases and two gray literature sources were searched up to 10 December 2018. All interventional and observational studies that contained information on the relevant population (adult patients with obesity and MS), intervention (receiving allogeneic FMT) and outcomes (metabolic parameters) were eligible. From 1096 unique citations, three randomized placebo-controlled studies (76 patients with obesity and MS, body mass index = 34.8 ± 4.1 kg/m2, fasting plasma glucose = 5.8 ± 0.7 mmol/L) were included for review. Studies reported mixed results with regards to improvement in metabolic parameters. Two studies reported improved peripheral insulin sensitivity (rate of glucose disappearance, RD) at 6 weeks in patients receiving donor FMT versus patients receiving the placebo control. In addition, one study observed lower HbA1c levels in FMT patients at 6 weeks. No differences in fasting plasma glucose, hepatic insulin sensitivity, body mass index (BMI), or cholesterol markers were observed between two groups across all included studies. While promising, the influence of FMT on long-term clinical endpoints needs to be further explored. Future studies are also required to better understand the mechanisms through which changes in gut microbial ecology and engraftment of microbiota affect metabolic outcomes for patients with obesity and MS. In addition, further research is needed to better define the optimal fecal microbial preparation, dosing, and method of delivery.

RevDate: 2019-09-29

Cammarota G, Ianiro G, Kelly CR, et al (2019)

International consensus conference on stool banking for faecal microbiota transplantation in clinical practice.

Gut pii:gutjnl-2019-319548 [Epub ahead of print].

Although faecal microbiota transplantation (FMT) has a well-established role in the treatment of recurrent Clostridioides difficile infection (CDI), its widespread dissemination is limited by several obstacles, including lack of dedicated centres, difficulties with donor recruitment and complexities related to regulation and safety monitoring. Given the considerable burden of CDI on global healthcare systems, FMT should be widely available to most centres.Stool banks may guarantee reliable, timely and equitable access to FMT for patients and a traceable workflow that ensures safety and quality of procedures. In this consensus project, FMT experts from Europe, North America and Australia gathered and released statements on the following issues related to the stool banking: general principles, objectives and organisation of the stool bank; selection and screening of donors; collection, preparation and storage of faeces; services and clients; registries, monitoring of outcomes and ethical issues; and the evolving role of FMT in clinical practice,Consensus on each statement was achieved through a Delphi process and then in a plenary face-to-face meeting. For each key issue, the best available evidence was assessed, with the aim of providing guidance for the development of stool banks in order to promote accessibility to FMT in clinical practice.

RevDate: 2019-09-27

Gong Y, Dong R, Gao X, et al (2019)

Neohesperidin Prevents Colorectal Tumorigenesis by Altering the Gut Microbiota.

Pharmacological research pii:S1043-6618(19)31054-0 [Epub ahead of print].

Neohesperidin (NHP), derived from citrus fruits, has attracted considerable interest due to its preventative and therapeutic effects on numerous diseases. However, little progress has been made in determining the exact function of NHP on tumorigenesis. In the current study, we found that NHP inhibited colorectal tumorigenesis in the APC min/+ transgenic mouse model, as well as inducing apoptosis and blocking angiogenesis in vivo. Our in-cell study suggested that this tumorigenic preventative effect of NHP is not due to the direct impact on tumor cells. Intriguingly, by utilizing 16 s rRNA gene-based microbiota sequencing, the relative abundance of Bacteroidetes was decreased, while Firmicutes and Proteobacteria were increased in the presence of NHP. Additionally, the fecal microbiota transplantation experiment further revealed that feeding with fecal of NHP-treated mice induced considerable inhibition of tumorigenesis, which indicates that the alteration of gut microbiota is responsible for NHP-mediated prevention of colorectal tumorigenesis. Thus, our study not only suggests the efficacy of NHP as a potent natural product for preventing colorectal cancer but also proposes a compelling model to connect the gut microbiota to the preventative effect of NHP on tumorigenesis.

RevDate: 2019-09-27

Smith AD, Foss ED, Zhang I, et al (2019)

Microbiota of MR1 deficient mice confer resistance against Clostridium difficile infection.

PloS one, 14(9):e0223025 pii:PONE-D-19-09497.

Clostridium difficile (Cd) infection (CDI) typically occurs after antibiotic usage perturbs the gut microbiota. Mucosa-associated invariant T cells (MAIT) are found in the gut and their development is dependent on Major histocompatibility complex-related protein 1 (MR1) and the host microbiome. Here we were interested in determining whether the absence of MR1 impacts resistance to CDI. To this end, wild-type (WT) and MR1-/- mice were treated with antibiotics and then infected with Cd spores. Surprisingly, MR1-/- mice exhibited resistance to Cd colonization. 16S rRNA gene sequencing of feces revealed inherent differences in microbial composition. This colonization resistance was transferred from MR1-/- to WT mice via fecal microbiota transplantation, suggesting that MR1-dependent factors influence the microbiota, leading to CDI susceptibility.

RevDate: 2019-09-27

Abu-Sbeih H, Y Wang (2019)

Management Considerations for Immune Checkpoint Inhibitor-Induced Enterocolitis Based on Management of Inflammatory Bowel Disease.

Inflammatory bowel diseases pii:5574910 [Epub ahead of print].

BACKGROUND: Immune checkpoint inhibitor therapy has significantly improved the outcomes of various advanced malignancies that were deemed unruly prior to its invention. Immune-mediated diarrhea and enterocolitis are among the most frequently encountered adverse events of immune checkpoint inhibitor therapy. Given the increasing use of these therapies in the treatment of an ever-growing number of malignancies, providing appropriate treatment for such adverse effects has become crucial.

METHODS: In this review, we summarize the current body of evidence concerning the management of immune-mediated diarrhea and enterocolitis. Additionally, management of immune-mediated diarrhea and enterocolitis is likened to that of inflammatory bowel disease, given the resemblance between both entities in pathogenesis and clinical features. Reviewing the literature raised several points regarding this devastating toxicity that still need further investigation by future efforts.

RESULTS: Endoscopic and histologic evaluation is pivotal in the assessment of immune-mediated diarrhea and enterocolitis and provides vital information regarding the severity of the disease to guide treatment. Corticosteroids are the main therapy for immune-mediated diarrhea and enterocolitis, with infliximab and vedolizumab as second-line agents. Recently, fecal microbiota transplantation has emerged as a treatment option for immune-mediated diarrhea and enterocolitis that is refractory to corticosteroids. Restarting immune checkpoint inhibitor therapy after resolution of immune-mediated diarrhea and enterocolitis carries a risk of recurrence that is mostly controllable with current immune-suppressive treatment.

CONCLUSIONS: Lastly, we propose a management algorithm for immune-mediated diarrhea and enterocolitis. Prospective research, preferably as collaborative efforts from oncology and gastroenterology specialists, is needed to refine the management of immune-mediated diarrhea and enterocolitis.

RevDate: 2019-09-27

Hu Y, Xiao HY, He C, et al (2019)

Fecal microbiota transplantation as an effective initial therapy for pancreatitis complicated with severe Clostridium difficile infection: A case report.

World journal of clinical cases, 7(17):2597-2604.

BACKGROUND: Moderately severe acute pancreatitis (MSAP) is a critical form of acute pancreatitis that is related with high morbidity and mortality. Severe Clostridium difficile infection (sCDI) is a serious and rare nosocomial diarrheal complication, especially in MSAP patients. Fecal microbiota transplantation (FMT) is a highly effective treatment for refractory and recurrent CDI (rCDI). However, knowledge regarding the initial use of FMT in patients suffering from sCDI is limited.

CASE SUMMARY: Here, we report an MSAP patient complicated with sCDI who was treated by FMT as a first-line therapy. The patient was a 51-year-old man who suffered from diarrhea in his course of acute pancreatitis. An enzyme immunoassay was performed to detect toxins, and the result was positive for toxin-producing C. difficile and toxin B and negative for C. difficile ribotype 027. The colonoscopy revealed pseudomembranous colitis. Due to these findings, sCDI was our primary consideration. Because the patient provided informed consent for FMT treatment, we initially treated the patient by FMT rather than metronidazole. Diarrhea resolved within 5 d after FMT. The patient remained asymptomatic, and the follow-up colonoscopy performed 40 d after discharge showed a complete recovery. Our case is the first reported in China.

CONCLUSION: This case explores the possibilities of initially using FMT to treat severe CDI. Moreover, FMT may become a critical component of the treatment for severe CDI in MSAP patients.

RevDate: 2019-09-27

Zheng P, Li Y, Wu J, et al (2019)

Perturbed Microbial Ecology in Myasthenia Gravis: Evidence from the Gut Microbiome and Fecal Metabolome.

Advanced science (Weinheim, Baden-Wurttemberg, Germany), 6(18):1901441 pii:ADVS1275.

Myasthenia gravis (MG) is a devastating acquired autoimmune disease. Emerging evidence indicates that the gut microbiome plays a key role in maintaining immune system homeostasis. This work reports that MG is characterized by decreased α-phylogenetic diversity, and significantly disturbed gut microbiome and fecal metabolome. The altered gut microbial composition is associated with fecal metabolome changes, with 38.75% of altered bacterial operational taxonomic units showing significant correlations with a range of metabolite biomarkers. Some microbes are particularly linked with MG severity. Moreover, a combination of microbial makers and their correlated metabolites enable discriminating MG from healthy controls (HCs) with 100% accuracy. To investigate whether disturbed gut mcirobiome might contribute to the onset of MG, germ-free (GF) mice are initially colonized with MG microbiota (MMb) or healthy microbiota (HMb), and then immunized in a classic mouse model of MG. The MMb mice demonstrate substantially impaired locomotion ability compared with the HMb mice. This effect could be reversed by cocolonizing GF mice with both MMb and HMb. The MMb mice also exhibit similar disturbances of fecal metabolic pathways as found in MG. Together these data demonstrate disturbances in microbiome composition and activity that are likely to be relevant to the pathogenesis of MG.

RevDate: 2019-09-27

Son DH, Park WJ, YJ Lee (2019)

Recent Advances in Anti-Aging Medicine.

Korean journal of family medicine, 40(5):289-296.

A rapidly aging population in Korea has led to increased attention in the field of anti-aging medicine. The purpose of anti-aging medicine is to slow, stop, or reverse the aging process and its associated effects, such as disability and frailty. Anti-aging medicine is emerging as a growing industry, but many supplements or protocols are available that do not have scientific evidence to support their claims. In this review, the mechanisms of action and the clinical implications of anti-aging interventions were examined and explained. Calorie restriction mimetics define compounds that imitate the outcome of calorie restriction, including an activator of AMP protein kinase (metformin), inhibitor of growth hormone/insulin-like growth factor-1 axis (pegvisomant), inhibitor of mammalian target of rapamycin (rapamycin), and activator of the sirtuin pathway (resveratrol). Hormonal replacement has also been widely used in the elderly population to improve their quality of life. Manipulating healthy gut microbiota through prebiotic/probiotics or fecal microbiota transplantation has significant potential in anti-aging medicine. Vitamin D is expected to be a primary anti-aging medicine in the near future due to its numerous positive effects in the elderly population.

RevDate: 2019-09-26

DeLong K, Bensouda S, Zulfiqar F, et al (2019)

Conceptual Design of a Universal Donor Screening Approach for Vaginal Microbiota Transplant.

Frontiers in cellular and infection microbiology, 9:306.

The success of fecal microbiota transplant (FMT) in treating recurrent Clostridioides difficile infection has led to growing excitement about the potential of using transplanted human material as a therapy for a wide range of diseases and conditions related to microbial dysbiosis. We anticipate that the next frontier of microbiota transplantation will be vaginal microbiota transplant (VMT). The composition of the vaginal microbiota has broad impact on sexual and reproductive health. The vaginal microbiota in the "optimal" state are one of the simplest communities, dominated by one of only a few species of Lactobacillus. Diversity in the microbiota and the concomitant depletion of lactobacilli, a condition referred to as bacterial vaginosis (BV), is associated with a wide range of deleterious effects, including increased risk of acquiring sexually transmitted infections and increased likelihood of having a preterm birth. However, we have very few treatment options available, and none of them curative or restorative, for "resetting" the vaginal microbiota to a more protective state. In order to test the hypothesis that VMT may be a more effective treatment option, we must first determine how to screen donors to find those with minimal risk of pathogen transmission and "optimal" vaginal microbiota for transplant. Here, we describe a universal donor screening approach that was implemented in a small pilot study of 20 women. We further characterized key physicochemical properties of donor cervicovaginal secretions (CVS) and the corresponding composition of the vaginal microbiota to delineate criteria for inclusion/exclusion. We anticipate that the framework described here will help accelerate clinical studies of VMT.

RevDate: 2019-09-25

Kim J, Lee H, An J, et al (2019)

Alterations in Gut Microbiota by Statin Therapy and Possible Intermediate Effects on Hyperglycemia and Hyperlipidemia.

Frontiers in microbiology, 10:1947.

Dysbiosis of the gut microbiota is a contributing factor for obesity-related metabolic diseases such as hyperglycemia and hyperlipidemia. Pharmacotherapy for metabolic diseases involves the modulation of gut microbiota, which is suggested to be a potential therapeutic target. In this study, the modulation of gut microbiota by statins (cholesterol-lowering drugs: atorvastatin and rosuvastatin) was investigated in an aged mouse model of high-fat diet-induced obesity, and the association between gut microbiota and immune responses was described. Atorvastatin and rosuvastatin significantly increased the abundance of the genera Bacteroides, Butyricimonas, and Mucispirillum. Moreover, the abundance of these genera was correlated with the inflammatory response, including levels of IL-1β and TGFβ1 in the ileum. In addition, oral fecal microbiota transplantation with fecal material collected from rosuvastatin-treated mouse groups improved hyperglycemia. From these results, the effect of statins on metabolic improvements could be explained by altered gut microbiota. Our findings suggest that the modulation of gut microbiota by statins has an important role in the therapeutic actions of these drugs.

RevDate: 2019-09-24

Li N, Tian HL, Chen QY, et al (2019)

[Efficacy analysis of fecal microbiota transplantation in the treatment of 2010 patients with intestinal disorders].

Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery, 22(9):861-868.

Objective: To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for intestinal disorders. Methods: A retrospectively descriptive cohort study was carried out. Clinical data of 2010 patients who underwent FMT and received follow-up for more than 3 months from May 2014 to November 2018 were collected, including 1,206 cases from Tongji University Shanghai Tenth People's Hospital and 804 cases from Nanjing Eastern Military General Hospital. Of the 2,010 patients, 797 were male and 1,213 were female, with a mean age of (49.4±16.5) years old. Inclusion criteria were those with indications for FMT and voluntary treatment of FMT. Pregnant or lactating women, patients with end-stage disease, cases who were participating or participated in other clinical trials within 3 months, and patients with previous bowel history of pathogen infection, oral antibiotics or proton pump inhibitors (PPI) for the recent2 weeks, and those at immunosuppressive state were excluded. Informed consent was obtained from the enrolled patients and their families. There were 1,356 cases of constipation, 175 cases of inflammatory bowel disease, 148 cases of chronic diarrhea, 127 cases of radiation enteritis, 119 cases of irritable bowel syndrome, and 85 cases of autism (complicating with intestinal disorders). FMT donor requirements: (1) 18 to 30 years old non-relatives, non-pregnant healthy adults with healthy lifestyle and good eating habits as volunteers to participate in fecal donation; (2) no administration of antibiotics within 3 months; (3) no chronic diseases such as constipation, irritable bowel syndrome, inflammatory bowel disease, etc., no autoimmune disease, not in immunosuppressive state, no history of malignant disease; (4) negative pathogen examination of infectious diseases (hepatitis B virus, hepatitis C virus, syphilis, HIV, etc.); (5) negative fecal examination (C.difficile, dysentery bacillus, Shigella, Campylobacter, parasites, etc.). The donor requirements after enrollment: (1) physical examination was reviewed once every two months, and the result still met the above requirements; (2) 16S rRNA sequencing was performed for every fecal donation in order to ensure that the composition and diversity of the fecal flora was stable and reliable. The preparation of the stool suspension referred to the Amsterdam criteria and the preparation process was less than 1 hour. The preparation of the FMT capsule was processed by pre-freezing the stool suspension after the preparation of the above suspension, and the frozen sample was transferred into a freeze dryer for freezing. The dried and lyophilized powder was encapsulated in capsules, and the capsule shell was made of acid-resistant hypromellose capsule (No.0) and pediatric-specific capsule (No.3), sealed and packaged in a-20℃ refrigerator. Three ways of accepting FMT treatment pathways included 6-day transplantation after the placement of the nasointestinal tube, 6-day oral FMT capsule transplantation and one-time transplantation through colonoscopy. Intestinal preparation (nasointestinal tube feeding of polyethylene glycol until watery stool) was carried out before transplantation. Other treatments were stopped during treatment and follow-up, and any medication was not recommended when necessary. Results: Of the 2010 patients, 1,497 cases received nasointestinal tube transplantation (nasointestinal tube group), 452 cases oral capsule transplantation (oral capsule group) and 61 cases colonoscopy (colonoscopy group). At 3 time points of 3, 12, and 36 months after FMT, the clinical cure rates and the clinical improvement rates were 41.3% (560/1 356), 35.2% (320/909), 31.4% (69/220), and 29.0% (393/1 356), 27.8% (253/909), 29.1% (64/220), respectively in constipation patients; 33.1% (58/175), 29.9% (35/117), 24.5% (12/49), and 31.4% (55/175), 27.4% (32/117), 57.1% (28/49), respectively in inflammatory bowel disease patients; 87.8% (130/148), 81.8% (81/99), 78.3% (36/46), and 8.1% (12/148), 7.1% (7/99), 4.3% (2/46), respectively in chronic diarrhea patients; 61.4% (78/127), 56.5% (48/85), 47.6% (20/42), and 21.2% (27/127), 15.3% (13/85), 14.3% (6/42), respectively in radiation enteritis patients; 53.8% (64/119), 45.0% (36/80), 6/15, and 21.0% (25/119), 26.2% (21/80), 4/15, respectively in irritable bowel syndrome patients; 23.5% (20/85), 22.8% (13/57), 20.0%(5/25), and 55.3% (47/85), 49.1% (28/57), 40.0% (10/25), respectively in autism patients. Meanwhile the clinical cure rates and the clinical improvement rates at 3, 12, and 36 months were 47.7% (714/1 497), 42.8% (425/994), 39.1% (128/327), and 29.1% (436/1 497), 27.0% (268/994), 28.1% (92/327), respectively in the nasointestinal tube group; 38.7% (175/452), 30.2% (91/301), 33.3% (16/48), and 24.3% (110/452), 26.2% (79/301), 25.0% (12/48), respectively in the oral capsule group; 34.4% (21/61), 32.7% (17/52), 18.2% (4/22), and 21.3% (13/61), 13.5% (7/52), 45.5% (10/22), respectively in colonoscopy group. No serious adverse events occurred during treatment and follow-up period. The adverse event of nasointestinal tube group presented higher ratio of discomfort in respiratorytract accounting for 13.1% (196/1497); the oral capsule group had a higher proportion of nausea and vomiting when swallowing capsules accounting for 7.1% (32/452); the colonoscopy group was mainly diarrhea, accounting for 37.7% (23/61). The above symptoms disappeared after the nasointestinal tube was removed, or after treatment ended, or within 1 to 3 days after hospitalization. Conclusion: FMT is a safe and effective method for the treatment of intestinal dysfunction.

RevDate: 2019-09-24

Cotter JM, Nicholson MR, LK Kociolek (2019)

An Infectious Diseases Perspective on Fecal Microbiota Transplantation for Clostridioides difficile Infection in Children.

Journal of the Pediatric Infectious Diseases Society pii:5573379 [Epub ahead of print].

Fecal microbiota transplantation (FMT) is efficacious for treatment of recurrent Clostridioides difficile infections (rCDIs). Pediatric experience with FMT for rCDIs is increasing, particularly at large centers. While retrospective studies suggest that FMT is generally safe in the short term, particularly in immunocompetent patients and with rigorous donor screening, additional large prospective studies are needed. This particularly includes those at high risk for infectious complications, such as immunocompromised hosts. Further, long-term implications of altering the intestinal microbiome with FMT are not well understood. The role of FMT in children, particularly in high-risk patients, will require continual reexamination with future availability of pediatric safety and efficacy data. This review summarizes key points for infectious diseases physicians to consider when evaluating a child for FMT.

RevDate: 2019-09-23

Guirro M, Costa A, Gual-Grau A, et al (2019)

Effects from diet-induced gut microbiota dysbiosis and obesity can be ameliorated by fecal microbiota transplantation: A multiomics approach.

PloS one, 14(9):e0218143 pii:PONE-D-19-14257.

Obesity and its comorbidities are currently considered an epidemic, and the involved pathophysiology is well studied. Hypercaloric diets are tightly related to the obesity etiology and also cause alterations in gut microbiota functionality. Diet and antibiotics are known to play crucial roles in changes in the microbiota ecosystem and the disruption of its balance; therefore, the manipulation of gut microbiota may represent an accurate strategy to understand its relationship with obesity caused by diet. Fecal microbiota transplantation, during which fecal microbiota from a healthy donor is transplanted to an obese subject, has aroused interest as an effective approach for the treatment of obesity. To determine its success, a multiomics approach was used that combined metagenomics and metaproteomics to study microbiota composition and function. To do this, a study was performed in rats that evaluated the effect of a hypercaloric diet on the gut microbiota, and this was combined with antibiotic treatment to deplete the microbiota before fecal microbiota transplantation to verify its effects on gut microbiota-host homeostasis. Our results showed that a high-fat diet induces changes in microbiota biodiversity and alters its function in the host. Moreover, we found that antibiotics depleted the microbiota enough to reduce its bacterial content. Finally, we assessed the use of fecal microbiota transplantation as a complementary obesity therapy, and we found that it reversed the effects of antibiotics and reestablished the microbiota balance, which restored normal functioning and alleviated microbiota disruption. This new approach could be implemented to support the dietary and healthy habits recommended as a first option to maintain the homeostasis of the microbiota.

RevDate: 2019-09-23

Lee JR, Huang J, Magruder M, et al (2019)

Butyrate-Producing Gut Bacteria and Viral Infections in Kidney Transplant Recipients: A Pilot Study.

Transplant infectious disease : an official journal of the Transplantation Society [Epub ahead of print].

BACKGROUND: The gut microbiome is being associated increasingly with development of infections besides C. difficile infection. A recent study found an association between butyrate-producing gut (BPG) bacteria and less frequent development of lower respiratory viral infections in allogeneic hematopoietic stem cell transplant recipients (Haak et al., Blood 131(26): 2978, 2018). In this investigation, we examine the relationship between the abundance of BPG bacteria and the development of viral infections in a cohort of kidney transplant recipients.

METHODS: We recruited 168 kidney transplant recipients who provided 510 fecal specimens in the first 3 months after transplantation and profiled the gut microbiota using 16S rRNA gene sequencing of the V4-V5 hypervariable region. We classified the kidney transplant recipients into higher BPG Bacteria Group and lower BPG Bacteria Group using the same criteria of 1% relative gut abundance of BPG bacteria as the Haak et al. study.

RESULTS: Administration of antibiotics against anaerobes was associated with a significant decrease in the relative gut abundance of BPG bacteria. The higher BPG Bacteria Group was associated with less development of respiratory viral infections (Hazard Ratio [HR]: 0.28, P=0.01) but not with less development of CMV viremia (HR: 0.38, P=0.13) or BK viremia (HR: 1.02, P= 0.98) at 2 years post-transplantation.

CONCLUSION: Our pilot investigation supports future validation of the relationship between high relative gut abundance of BPG bacteria and decreased risk for development of respiratory viral infections.

RevDate: 2019-09-23

Yuan J, Chen C, Cui J, et al (2019)

Fatty Liver Disease Caused by High-Alcohol-Producing Klebsiella pneumoniae.

Cell metabolism pii:S1550-4131(19)30447-4 [Epub ahead of print].

The underlying etiology of nonalcoholic fatty liver disease (NAFLD) is believed to be quite varied. Changes in the gut microbiota have been investigated and are believed to contribute to at least some cases of the disease, though a causal relationship remains unclear. Here, we show that high-alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) is associated with up to 60% of individuals with NAFLD in a Chinese cohort. Transfer of clinical isolates of HiAlc Kpn by oral gavage into mice induced NAFLD. Likewise, fecal microbiota transplant (FMT) into mice using a HiAlc-Kpn-strain-containing microbiota isolated from an individual with NASH induced NAFLD. However, selective elimination of the HiAlc Kpn strain before FMT prevented NAFLD in the recipient mice. These results suggest that at least in some cases of NAFLD an alteration in the gut microbiome drives the condition due to excess endogenous alcohol production.

RevDate: 2019-09-21

Meroni M, Longo M, P Dongiovanni (2019)

Alcohol or Gut Microbiota: Who Is the Guilty?.

International journal of molecular sciences, 20(18): pii:ijms20184568.

Alcoholic liver disease (ALD), a disorder caused by excessive alcohol intake represents a global health care burden. ALD encompasses a broad spectrum of hepatic injuries including asymptomatic steatosis, alcoholic steatohepatitis (ASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The susceptibility of alcoholic patients to develop ALD is highly variable and its progression to more advanced stages is strongly influenced by several hits (i.e., amount and duration of alcohol abuse). Among them, the intestinal microbiota and its metabolites have been recently identified as paramount in ALD pathophysiology. Ethanol abuse triggers qualitative and quantitative modifications in intestinal flora taxonomic composition, mucosal inflammation, and intestinal barrier derangement. Intestinal hypermeability results in the translocation of viable pathogenic bacteria, Gram-negative microbial products, and pro-inflammatory luminal metabolites into the bloodstream, further corroborating the alcohol-induced liver damage. Thus, the premise of this review is to discuss the beneficial effect of gut microbiota modulation as a novel therapeutic approach in ALD management.

RevDate: 2019-09-19

Villéger R, Lopès A, Carrier G, et al (2019)

Intestinal Microbiota: A Novel Target to Improve Anti-Tumor Treatment?.

International journal of molecular sciences, 20(18): pii:ijms20184584.

Recently, preclinical and clinical studies targeting several types of cancer strongly supported the key role of the gut microbiota in the modulation of host response to anti-tumoral therapies such as chemotherapy, immunotherapy, radiotherapy and even surgery. Intestinal microbiome has been shown to participate in the resistance to a wide range of anticancer treatments by direct interaction with the treatment or by indirectly stimulating host response through immunomodulation. Interestingly, these effects were described on colorectal cancer but also in other types of malignancies. In addition to their role in therapy efficacy, gut microbiota could also impact side effects induced by anticancer treatments. In the first part of this review, we summarized the role of the gut microbiome on the efficacy and side effects of various anticancer treatments and underlying mechanisms. In the second part, we described the new microbiota-targeting strategies, such as probiotics and prebiotics, antibiotics, fecal microbiota transplantation and physical activity, which could be effective adjuvant therapies developed in order to improve anticancer therapeutic efficiency.

RevDate: 2019-09-18

Castaño-Rodríguez N, Paramsothy S, NO Kaakoush (2019)

Promise of Fecal Microbiota Transplantation Therapy in Pouchitis.

RevDate: 2019-09-18

Du H, Kuang TT, Qiu S, et al (2019)

Fecal medicines used in traditional medical system of China: a systematic review of their names, original species, traditional uses, and modern investigations.

Chinese medicine, 14:31 pii:253.

In China, the medical use of fecal matter (fresh fecal suspension or dry feces) can be dated back to the fourth century, approximately 1700 years ago. In long-term clinical practice, Chinese doctors have accumulated unique and invaluable medical experience in the use of fecal materials. In view of their good curative effect and medicinal potential, fecal medicines should be paid much attention. This study aimed to provide the first comprehensive data compilation of fecal medicines used in various Chinese traditional medical systems by bibliographic investigation of 31 medicine monographs and standards. A total of 54 fecal medicines were found to be used in 14 traditional Chinese medical systems. Their names, original species, medicinal forms, and traditional uses were described in detail. These fecal medicines were commonly used to treat gastrointestinal, nervous system, skin, and gynecological diseases. Commonly used fecal medicines include Wu-Ling-Zhi, Jiu-Fen and Hei-Bing-Pian. The information summarized in this study can provide a good reference for the development and utilization of fecal medicines. Further studies are necessary to prove their medicinal value, identify their active ingredients, and elucidate their mechanisms of action so that more people can accept these special medicines.

RevDate: 2019-09-18

Wu R, Mei X, Ye Y, et al (2019)

Zn(II)-curcumin solid dispersion impairs hepatocellular carcinoma growth and enhances chemotherapy by modulating gut microbiota-mediated zinc homeostasis.

Pharmacological research pii:S1043-6618(19)30854-0 [Epub ahead of print].

Zinc(II) complexes of curcumin display moderate cytotoxicity towards cancer cells at low micromolar concentrations. However, the clinical use of zinc(II) complexes is hampered by hydrolytic insolubility and poor bioavailability and their anticancer mechanisms remain unclear. Here, we investigated the efficacy and mechanism of action of a polyvinylpyrrolidone (PVP-k30)-based solid dispersion of Zn(II)-curcumin (ZnCM-SD) against hepatocellular carcinoma (HCC) in vitro and in vivo. In vitro assays revealed ZnCM-SD not only reduced the viability of HepG2 cells and SK-HEP1 cells in a dose-dependent manner, but also potently and synergistically enhanced cell growth inhibition and cell death in response to doxorubicin by regulating cellular zinc homeostasis. ZnCM-SD was internalized into the cells via non-specific endocytosis and degraded to release curcumin and Zn2+ ions within cells. The anticancer effects also occur in vivo in animals following the oral administration of ZnCM-SD, without significantly affecting the weight of the animals. Interestingly, ZnCM-SD did not reduce tumor growth or affect zinc homeostasis in HepG2-bearing mice after gut microbiome depletion. Moreover, administration of ZnCM-SD alone or in combination with doxorubicin significantly attenuated gut dysbiosis and zinc dyshomeostasis in a rat HCC model. Notably, fecal microbiota transplantation revealed the ability of ZnCM-SD to regulate zinc homeostasis and act as a chemosensitizer for doxorubicin were dependent on the gut microbiota. The crucial role of the gut microbiota in the chemosensitizing ability of ZnCM-SD was confirmed by broad-spectrum antibiotic treatment. Collectively, ZnCM-SD could represent a simple, well-tolerated, safe, effective therapy and function as a novel chemosensitizing agent for cancer.

RevDate: 2019-09-18

Lavazza A, VA Sironi (2019)

Are we Ready for a "Microbiome-Guided Behaviour" Approach?.

Cambridge quarterly of healthcare ethics : CQ : the international journal of healthcare ethics committees, 28(4):708-724.

The microbiome is proving to be increasingly important for human brain functioning. A series of recent studies have shown that the microbiome influences the central nervous system in various ways, and consequently acts on the psychological well-being of the individual by mediating, among others, the reactions of stress and anxiety. From a specifically neuroethical point of view, according to some scholars, the particular composition of the microbiome-qua microbial community-can have consequences on the traditional idea of human individuality. Another neuroethical aspect concerns the reception of this new knowledge in relation to clinical applications. In fact, attention to the balance of the microbiome-which includes eating behavior, the use of psychobiotics and, in the treatment of certain diseases, the use of fecal microbiota transplantation-may be limited or even prevented by a biased negative attitude. This attitude derives from a prejudice related to everything that has to do with the organic processing of food and, in general, with the human stomach and intestine: the latter have traditionally been regarded as low, dirty, contaminated and opposed to what belongs to the mind and the brain. This biased attitude can lead one to fail to adequately consider the new anthropological conceptions related to the microbiome, resulting in a state of health, both physical and psychological, inferior to what one might have by paying the right attention to the knowledge available today. Shifting from the ubiquitous high-low metaphor (which is synonymous with superior-inferior) to an inside-outside metaphor can thus be a neuroethical strategy to achieve a new and unbiased reception of the discoveries related to the microbiome.

RevDate: 2019-09-18

Schwartz DJ, Rebeck ON, G Dantas (2019)

Complex interactions between the microbiome and cancer immune therapy.

Critical reviews in clinical laboratory sciences [Epub ahead of print].

Immuno-oncology has rapidly grown in the last thirty years, and immunotherapeutic agents are now approved to treat many disparate cancers. Immune checkpoint inhibitors (ICIs) are employed to augment cytotoxic anti-cancer activity by inhibiting negative regulatory elements of the immune system. Modulating the immune system to target neoplasms has improved survivability of numerous cancers in many individuals, but forecasting outcomes post therapy is difficult due to insufficient predictive biomarkers. Recently, the tumor and gastrointestinal microbiome and immune milieu have been investigated as predictors and influencers of cancer immune therapy. In this review, we discuss: (1) ways to measure the microbiome including relevant bioinformatic analyses, (2) recent developments in animal studies and human clinical trials utilizing gut microbial composition and function as biomarkers of cancer immune therapy response and toxicity, and (3) using prebiotics, probiotics, postbiotics, antibiotics, and fecal microbiota transplant (FMT) to modulate immune therapy. We discuss the respective benefits of 16S ribosomal RNA (rRNA) gene and shotgun metagenomic sequencing including important considerations in obtaining samples and in designing and interpreting human and animal microbiome studies. We then focus on studies discussing the differences in response to ICIs in relation to the microbiome and inflammatory mediators. ICIs cause colitis in up to 25% of individuals, and colitis is often refractory to common immunosuppressive medications. Researchers have measured microbiota composition prior to ICI therapy and correlated baseline microbiota composition with efficacy and colitis. Certain bacterial taxa that appear to enhance therapeutic benefit are also implicated in increased susceptibility to colitis, alluding to a delicate balance between pro-inflammatory tumor killing and anti-inflammatory protection from colitis. Pre-clinical and clinical models have trialed probiotic administration, e.g. Bifidobacterium spp. or FMT, to treat colitis when immune suppressive agents fail. We are excited about the future of modulating the microbiome to predict and influence cancer outcomes. Furthermore, novel therapies employed for other illnesses including bacteriophage and genetically-engineered microbes can be adapted in the future to promote increased advancements in cancer treatment and side effect management.

RevDate: 2019-09-17
CmpDate: 2019-09-17

Mullish BH, Quraishi MN, Segal JP, et al (2018)

The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.

The Journal of hospital infection, 100 Suppl 1:S1-S31.

RevDate: 2019-09-18
CmpDate: 2019-09-18

Leung V, Vincent C, Edens TJ, et al (2018)

Reply to Davido et al.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 66(8):1317-1318.

RevDate: 2019-09-16

Faivre B, Bellenger J, Rieu A, et al (2019)

Disentangling the effect of host genetics and gut microbiota on resistance to an intestinal parasite.

International journal for parasitology pii:S0020-7519(19)30206-1 [Epub ahead of print].

Resistance to infection is a multifactorial trait, and recent work has suggested that the gut microbiota can also contribute to resistance. Here, we performed a fecal microbiota transplant (FMT) to disentangle the contribution of the gut microbiota and host genetics as drivers of resistance to the intestinal nematode Heligmosomoides polygyrus. We transplanted the microbiota of a strain of mice (SJL), resistant to H. polygyrus, into a susceptible strain (CBA) and vice-versa. We predicted that if the microbiota shapes resistance to H. polygyrus, the FMT should reverse the pattern of resistance between the two host strains. The two host strains had different microbiota diversities and compositions before the start of the experiment, and the FMT altered the microbiota of recipient mice. One mouse strain (SJL) was more resistant to colonization by the heterologous microbiota, and it maintained its resistance profile to H. polygyrus (lower parasite burden) independently of the FMT. On the contrary, CBA mice harbored parasites with lower fecundity during the early stage of the infection, and had an up-regulated expression of the cytokine IL-4 (a marker of H. polygyrus resistance) after receiving the heterologous microbiota. Therefore, while host genetics remains the main factor shaping the pattern of resistance to H. polygyrus, the composition of the gut microbiota also seems to play a strain-specific role.

RevDate: 2019-09-16
CmpDate: 2019-09-16

Li X, Chen P, Zhang P, et al (2019)

Protein-Bound β-glucan from Coriolus Versicolor has Potential for Use Against Obesity.

Molecular nutrition & food research, 63(7):e1801231.

SCOPE: The prevalence of obesity and related disorders has vastly increased throughout the world and prevention of such circumstances thus represents a major challenge. Here, it has been shown that one protein-bound β-glucan (PBG) from the edible mushroom Coriolus versicolor can be a potent anti-obesity component.

METHODS AND RESULTS: PBG can reduce obesity and metabolic inflammation in mice fed with a high-fat diet (HFD). Gut microbiota analysis reveals that PBG markedly increases the abundance of Akkermansia muciniphila, although it does not rescue HFD-induced change in the Firmicutes to Bacteroidetes ratio. It appears that PBG alters host physiology and creates an intestinal microenvironment favorable for A. muciniphila colonization. Fecal transplants from PBG-treated animals in part reduce obesity in recipient HFD-fed mice. Further, PBG is shown to upregulate expression of a set of genes related to host metabolism in microbiota-depleted mice.

CONCLUSION: The data highlight that PBG may exert its anti-obesity effects through a mirobiota-dependent (richness of specific microbiota) and -independent (modulation of host metabolism) manner. The fact that C. versicolor PBGs are approved oral immune boosters in cancers and chronic hepatitis with well-established safety profiles may accelerate PBG as a novel use for obesity treatment.

RevDate: 2019-09-14

McCormack UM, Curião T, Metzler-Zebeli BU, et al (2019)

Seeking to improve feed efficiency in pigs through microbial modulation via fecal microbiota transplantation in sows and dietary supplementation of offspring with inulin.

Applied and environmental microbiology pii:AEM.01255-19 [Epub ahead of print].

As previous studies have demonstrated a link between the porcine intestinal microbiome and feed efficiency (FE), microbiota manipulation may offer a means of improving FE in pigs. A fecal microbiota transplantation procedure (FMTp), using fecal extracts from highly feed efficient pigs, was performed in pregnant sows (n=11), with a control group (n=11) receiving no FMTp. At weaning, offspring were allocated, within sow treatment, to 1) control (n=67; no dietary supplement) or 2) inulin (n=65; 6-week dietary inulin supplementation) treatments. The sow FMTp, alone or in combination with offspring inulin supplementation, reduced offspring body weight by 8.1-10.6 Kg at ∼140 days of age, but there was no effect on feed intake. It resulted in better FE, higher bacterial diversity and higher relative abundances of potentially beneficial bacterial taxa (Fibrobacter, Prevotella) in offspring. Due to FMTp and/or inulin supplementation, relative abundance of potential pathogens (Chlamydia, Treponema) in the ileum, and cecal concentrations of butyric acid were significantly lower. Maternal FMTp led to a greater number of jejunal goblet cells in offspring. Inulin supplementation alone did not affect growth or FE, but up-regulated duodenal genes linked to glucose and volatile fatty acid homeostasis and increased mean platelet volume, but reduced ileal propionic acid, granulocyte counts, and serum urea. Overall, FMTp in pregnant sows, with/without offspring dietary inulin supplementation, beneficially modulated offspring intestinal microbiota (albeit mostly low relative abundance taxa) and associated physiological parameters. Although FE was improved, the detrimental effect on growth limits the application of this FMTp/inulin strategy in commercial pig production.IMPORTANCE As previous research suggests a link between microbiota and FE, modulation of the intestinal microbiome may be effective in improving FE in pigs. The FMTp in gestating sows, alone/in combination with offspring post-weaning dietary inulin supplementation, achieved improvements in FE, and resulted in higher relative abundance of intestinal bacteria associated with fiber degradation, and lower relative abundance of potential pathogens. However, there was a detrimental effect on growth, although this may not be wholly attributable to microbiota transplantation, as antibiotic and other interventions were also part of the FMT regime. Therefore, further work with additional control groups is needed to disentangle the effects of each component of the FMTp in order to develop a regime with practical applications in pig production. Additional research based on findings from this study may also identify specific dietary supplements for promotion/maintenance of the microbiota transferred via maternal FMTp, thereby optimizing pig growth and FE.

RevDate: 2019-09-13

Zhao W, Hu Y, Li C, et al (2019)

Transplantation of fecal microbiota from patients with alcoholism induces anxiety/depression behaviors and decreases brain mGluR1/PKC ε levels in mouse.

BioFactors (Oxford, England) [Epub ahead of print].

Recent studies have revealed that the gut microbiota participates in the psychiatric behavior changes in disorders associated with alcohol. But it still remains unknown whether alcoholism is involved in changes in gut microbiota and its underlying mechanism is also not clear. Here, we tested the gut microbiota of patients with alcoholism and conducted fecal microbiota transplantation (FMT) from patients with alcoholism to C57BL/6J mice whose gut microbiota had been sharply suppressed with antibiotics (ABX). Then we evaluated their alcohol preference degree, anxiety, and depression-like behaviors and social interaction behaviors, together with molecular changes in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc). Our data indicated that the gut microbiota of patients with alcoholism was drastically different from those of the healthy adults. The abundance of p_Firmicutes was significantly increased whereas p_Bacteroidetes was decreased. Compared to mice transplanted with fecal microbiota from healthy male adults, the mice accepting fecal microbiota from patients with alcoholism showed (a) anxiety-like and depression-like behaviors, (b) decreased social interaction behaviors, (c) spontaneous alcohol preference, and (d) decreased brain-derived neurotrophic factor (BDNF), alpha 1 subunit of GABA type A receptor (α1GABAA R) in mPFC and decreased metabotropic glutamate receptors 1 (mGluR1), protein kinase C (PKC) ε in NAc. Overall, our results suggest that fecal microbiota from patients with alcoholism did induce a status like alcohol dependence in C57BL/6J mice. The decreased expression of BDNF, α1GABAA R, and mGluR1/ PKC ε may be the underlying mechanism.

RevDate: 2019-09-13

Wu X, Dai M, Buch H, et al (2019)

The recognition and attitudes of postgraduate medical students toward fecal microbiota transplantation: a questionnaire study.

Therapeutic advances in gastroenterology, 12:1756284819869144 pii:10.1177_1756284819869144.

Background: Physicians and medical students in the world do not have high awareness of fecal microbiota transplantation (FMT). This study aimed to explore the recognition and attitude of postgraduate medical students towards FMT and to create awareness for it.

Methods: A self-administered questionnaire was distributed to first-year Chinese postgraduate medical students across six medical universities. Basic descriptive statistical analyses were performed.

Results: A total of 1828 eligible questionnaires were included into analysis. 47.76% of students did not know FMT prior to this survey. Respondents with a high-level recognition of FMT were more willing to donate feces or receive FMT therapy than those with a low-level recognition (80.26% vs. 69.62%, p = 0.000 and 56.80% vs. 41.45%, p = 0.000). The respondents from a leading institution of FMT in China showed better awareness compared with others, and 42.26% of them knew about FMT from medical lectures. The main reasons for respondents not supporting FMT were: limited reported clinical evidence (67.94%), raw technology (42.56%), and lack of analysis of patient willingness or cost-effectiveness (36.71%). However, the life-saving value (84.41%), the automatic purification system (38.68%), low expenses (36.00%), and convenient delivering ways (35.67%) were the major considerations for supporting FMT.

Conclusions: This study revealed the low recognition level of postgraduate medical students about FMT. Therefore, medical education should not neglect the knowledge of FMT. Studies of FMT and standardized FMT should be carried out to promote its development.

RevDate: 2019-09-12

Schepici G, Silvestro S, Bramanti P, et al (2019)

The Gut Microbiota in Multiple Sclerosis: An Overview of Clinical Trials.

Cell transplantation [Epub ahead of print].

Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, and degenerative disease that affects the central nervous system. A recent study showed that interaction between the immune system and the gut microbiota plays a crucial role in the development of MS. This review reports the clinical studies carried out in recent years that aimed to evaluate the composition of the microbiota in patients with relapsing-remitting MS (RR-MS). We also report what is available in the literature regarding the effectiveness of fecal microbiota transplantation and the role of the diet in restoring the intestinal bacterial population. Studies report that patients with RR-MS have a microbiota that, compared with healthy controls, has higher amounts of Pedobacteria, Flavobacterium, Pseudomonas, Mycoplana, Acinetobacter, Eggerthella, Dorea, Blautia, Streptococcus and Akkermansia. In contrast, MS patients have a microbiota with impoverished microbial populations of Prevotella, Bacteroides, Parabacteroides, Haemophilus, Sutterella, Adlercreutzia, Coprobacillus, Lactobacillus, Clostridium, Anaerostipes and Faecalibacterium. In conclusion, the restoration of the microbial population in patients with RR-MS appears to reduce inflammatory events and the reactivation of the immune system.

RevDate: 2019-09-12

Prochazkova P, Roubalova R, Dvorak J, et al (2019)

Microbiota, Microbial Metabolites, and Barrier Function in A Patient with Anorexia Nervosa after Fecal Microbiota Transplantation.

Microorganisms, 7(9): pii:microorganisms7090338.

The change in the gut microbiome and microbial metabolites in a patient suffering from severe and enduring anorexia nervosa (AN) and diagnosed with small intestinal bacterial overgrowth syndrome (SIBO) was investigated. Microbial gut dysbiosis is associated with both AN and SIBO, and therefore gut microbiome changes by serial fecal microbiota transplantation (FMT) is a possible therapeutic modality. This study assessed the effects of FMT on gut barrier function, microbiota composition, and the levels of bacterial metabolic products. The patient treatment with FMT led to the improvement of gut barrier function, which was altered prior to FMT. Very low bacterial alpha diversity, a lack of beneficial bacteria, together with a great abundance of fungal species were observed in the patient stool sample before FMT. After FMT, both bacterial species richness and gut microbiome evenness increased in the patient, while the fungal alpha diversity decreased. The total short-chain fatty acids (SCFAs) levels (molecules presenting an important source of energy for epithelial gut cells) gradually increased after FMT. Contrarily, one of the most abundant intestinal neurotransmitters, serotonin, tended to decrease throughout the observation period. Overall, gut microbial dysbiosis improvement after FMT was considered. However, there were no signs of patient clinical improvement. The need for an in-depth analysis of the donor´s stool and correct selection pre-FMT is evident.

RevDate: 2019-09-12
CmpDate: 2019-09-12

Enck P, N Mazurak (2019)

[Microbiota and irritable bowel syndrome: A critical inventory].

Zeitschrift fur Gastroenterologie, 57(7):859-870.

This narrative review critically explores the role of the gut microbiota in functional bowel disorders of IBS-type. Starting with changes in the microbiota composition and diversity, as they have been often found in correlative IBS studies, it raises the question of cause and consequence, of sensitivity and specificity of findings in comparison to other diseases, and of the scientific and clinical options to manipulate the microbiota. This includes a discussion of pre- and probiotics and antibiotics as well as the role of nutrition and the microbiota exchange with fecal microbiota transfer (FMT). For IBS, most of these strategies have not been found to be successful therapies. This may be due to the heterogeneity of the disease itself, but eventually also due to the concepts of microbiological research, e. g., the term dysbiosis, or in methodological differences of the molecular-genetic research that are not visible in the published papers. Future studies should aim to identify those factors that may explain and predict the response to such therapies.

RevDate: 2019-09-12
CmpDate: 2019-09-12

Mullish BH, Quraishi MN, Segal JP, et al (2018)

Introduction to the joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) faecal microbiota transplant guidelines.

The Journal of hospital infection, 100(2):130-132.

RevDate: 2019-09-10

Lee H, Kim J, An J, et al (2019)

Downregulation of IL-18 Expression in the Gut by Metformin-induced Gut Microbiota Modulation.

Immune network, 19(4):e28 pii:2019190406.

IL-18 is a crucial pro-inflammatory cytokine that mediates chronic intestinal inflammation. Metformin, an anti-diabetic drug, was reported to have ameliorative effects on inflammatory bowel disease. Recently, the mechanism of action of metformin was explained as a modulation of gut microbiota. In this study, fecal microbiota transplantation (FMT) using fecal material from metformin-treated mice was found to upregulate the expression of GLP-1 and pattern-recognition receptors TLR1 and TLR4 for the improvement in hyperglycemia caused by a high-fat diet. Further, FMT downregulated the expression of the inflammatory cytokine IL-18. Within the genera Akkermansia, Bacteroides, and Butyricimonas, which were promoted by metformin therapy, Butyricimonas was found to be consistently abundant following FMT. Our findings suggest that modulation of gut microbiota is a key factor for the anti-inflammatory effects of metformin which is used for the treatment of hyperglycemia.

RevDate: 2019-09-09

Philips CA, Augustine P, Yerol PK, et al (2019)

Severe alcoholic hepatitis: current perspectives.

Hepatic medicine : evidence and research, 11:97-108 pii:197933.

Severe acute alcoholic hepatitis (AH) is a catastrophic disease in the natural history of alcoholic liver disease with a very high 180-day mortality. It can present as acute on chronic liver failure with worse prognosis in the presence of infections and higher grades of liver disease severity. The clinical scenario involves a patient with a recent history of heavy alcohol consumption within three months of presentation with jaundice and characteristic liver enzyme elevation pattern with coagulopathy, hepatic encephalopathy, variceal bleeding and sepsis that results in extrahepatic organ failures. Several liver disease severities and therapy response indicators are in clinical use. Even though not approved, the only recommended treatment option for patients with severe AH is corticosteroids, which is without long term survival benefit. Novel efficacious treatment options awaiting high-quality multi-center studies include liver transplantation (involves strict selection criteria), growth factor therapy and fecal microbiota transplantation. In this exhaustive review, we discuss the definitions, disease severity, histopathology, and treatment options - past, present, and future, in patients with severe alcoholic hepatitis.

RevDate: 2019-09-09

Hu Y, B Lyu (2019)

[Development and prospects of fecal microbiota transplantation].

Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences, 48(3):342-346.

RevDate: 2019-09-09
CmpDate: 2019-09-09

Endres K, KH Schäfer (2018)

Influence of Commensal Microbiota on the Enteric Nervous System and Its Role in Neurodegenerative Diseases.

Journal of innate immunity, 10(3):172-180.

When thinking about neurodegenerative diseases, the first symptoms that come to mind are loss of memory and learning capabilities, which all resemble hallmarks of manifestation of such diseases in the central nervous system (CNS). However, the gut comprises the largest nervous system outside the CNS that is autonomously active and in close interplay with its microbiota. Therefore, the enteric nervous system (ENS) might serve as an indicator of degenerative pathomechanisms that also affect the CNS. On the other hand, it might offer an entry point for devastating influences from the microbial community or - conversely - for therapeutic approaches via gut commensals. Within the last years, the ENS and gut microbiota therefore have sparked the interest of researchers of CNS diseases and we here report on recent findings and open questions, especially with regard to Alzheimer and Parkinson diseases.

RevDate: 2019-09-07

Madoff SE, Urquiaga M, Alonso CD, et al (2019)

Prevention of recurrent Clostridioides difficile infection: A systematic review of randomized controlled trials.

Anaerobe pii:S1075-9964(19)30158-1 [Epub ahead of print].

Recurrent Clostridioides (formerly Clostridium) difficile infection (rCDI) is common, and patients who have had one recurrence are more likely to have multiple recurrences. Frequent recurrences have been associated with increased morbidity and mortality, high healthcare costs, and lower quality of life. In this review, we compare the efficacy of interventions designed to prevent rCDI. We performed a systematic review of the English literature, including randomized controlled trials (RCTs) that evaluated rCDI as an outcome. Studies were included irrespective of patient demographics, disease severity, type of intervention, comparator used, or time-point of outcome evaluation. We performed a comprehensive literature search with the assistance of a research librarian. Two reviewers independently extracted data and assessed risk of bias. Our search yielded 38 RCTs (8,102 participants). Nineteen RCTs (3743 subjects) evaluated antibiotics, eight fecal microbiota transplantation (FMT) (582 subjects), three monoclonal antibodies (MAbs) (2805 subjects), and eight probiotics, prebiotics, or non-antibiotic polymers (972 subjects). The antibiotic and FMT therapies that demonstrated efficacy in rCDI prevention included: fidaxomicin (when compared to a ten-day vancomycin course) and FMT administered by nasogastric tube (when compared to a fourteen-day vancomycin course and a fourteen-day vancomycin course plus bowel lavage). Actoxumab (MAb against C. difficile toxin A; CDA1) plus bezlotoxumab (MAb against C. difficile toxin B; CDB1) in combination or bezlotoxumab alone appeared to be more effective in preventing rCDI compared to actoxumab alone. Of the prebiotics, probiotics, and nonantibiotic polymers, oligofructose, Saccharomyces boulardii, and the nontoxigenic C. difficile strain M3 were the most efficacious for rCDI prevention. Thirty-eight RCTs (>8,000 participants) evaluating treatment modalities for CDI were examined for efficacy in prevention of rCDI. Several CDI-specific antibiotics, FMT modalities, monoclonal antibodies, and various prebiotics and probiotics demonstrated a reduction in risk of rCDI with the greatest risk reduction observed with FMT and monoclonal antibody therapy. It is notable that the comparators in these studies were very different from one another and the relative risk reduction of rCDI may not be directly comparable from one study to the next.

RevDate: 2019-09-07

Luo Y, Lucas AL, AM Grinspan (2019)

Fecal Transplants by Colonoscopy and Capsules Are Cost-Effective Strategies for Treating Recurrent Clostridioides difficile Infection.

Digestive diseases and sciences pii:10.1007/s10620-019-05821-1 [Epub ahead of print].

BACKGROUND: Recurrent Clostridioides difficile infections (CDIs) occur frequently and pose a substantial economic burden on the US healthcare system. The landscape for the treatment of CDI is evolving.

AIM: To elucidate the most cost-effective strategy for managing recurrent CDI.

METHODS: A decision tree analysis was created from a modified third-party payer's perspective to compare the cost-effectiveness of five strategies for patients experiencing their first CDI recurrence: oral vancomycin, fidaxomicin, fecal microbiota transplant (FMT) via colonoscopy, FMT via oral capsules, and a one-time infusion of bezlotoxumab with vancomycin. Effectiveness measures were quality-adjusted life years (QALY). A willingness-to-pay (WTP) threshold of $100,000 per QALY was set. One-way and probabilistic sensitivity analyses were performed.

RESULTS: Base-case analysis showed that FMT via colonoscopy was associated with the lowest cost at $5250 and that FMT via capsules was also a cost-effective strategy with an incremental cost-effectiveness ratio (ICER) of $31205/QALY. Sensitivity analyses demonstrated that FMT delivered by oral capsules and colonoscopy was comparable cost-effective modalities. At its current cost and effectiveness, bezlotoxumab was not a cost-effective strategy.

CONCLUSIONS: FMT via oral capsules and colonoscopy is both cost-effective strategies to treat the first recurrence of CDI. Further real-world economic studies are needed to understand the cost-effectiveness of all available strategies.

RevDate: 2019-09-07

Chong PP, AY Koh (2019)

The gut microbiota in transplant patients.

Blood reviews pii:S0268-960X(19)30030-X [Epub ahead of print].

Solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients are at increased risk for developing infections due to underlying immunosuppression. Antibiotic use, and in HSCT recipients, the use of preparative regimens prior to transplantation can deplete gut commensal bacteria, resulting in intestinal dysbiosis. Emerging evidence in transplant patients, particularly HSCT, suggest that disturbances in gut microbiota populations are associated with a number of adverse outcomes. Here, we review the outcomes of HSCT and SOT recipients with gut microbiota imbalance or dysbiosis, explore the nascent field of gut microbiome therapeutic approaches including fecal microbiota transplantation and the use of precision probiotics in HSCT and SOT recipients.

RevDate: 2019-09-06

Mashaqi S, D Gozal (2019)

Obstructive Sleep Apnea and Systemic Hypertension: Gut Dysbiosis as the Mediator?.

Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine pii:jc-18-00726 [Epub ahead of print].

INTRODUCTION: Obstructive sleep apnea (OSA) and systemic hypertension (SH) are common and interrelated diseases. It is estimated that approximately 75% of treatment-resistant hypertension cases have an underlying OSA. Exploration of the gut microbiome is a new advance in medicine that has been linked to many comorbid illnesses, including SH and OSA. Here, we will review the literature in SH and gut dysbiosis, OSA and gut dysbiosis, and whether gut dysbiosis is common in both conditions.

METHODS: We reviewed the National Center for Biotechnology Information database, including PubMed and PubMed Central. We identified a total of 230 articles. The literature search was conducted using the phrase "obstructive sleep apnea and gut dysbiosis." Only original research articles were included. This yielded a total of 12 articles.

RESULTS: Most of the research conducted in this field was on animal models, and almost all trials confirmed that intermittent hypoxia models resulted in gut dysbiosis. Gut dysbiosis, however, can cause a state of low-grade inflammation through damage to the gut wall barrier resulting in "leaky gut." Neuroinflammation is a hallmark of the pathophysiology of OSA-induced SH.

CONCLUSIONS: Gut dysbiosis seems to be an important factor in the pathophysiology of OSA-induced hypertension. Reversing gut dysbiosis at an early stage through prebiotics and probiotics and fecal microbiota transplantation combined with positive airway pressure therapy may open new horizons of treatment to prevent SH. More studies are needed in humans to elicit the effect of positive airway pressure therapy on gut dysbiosis.

RevDate: 2019-09-06
CmpDate: 2019-09-06

Sircana A, Framarin L, Leone N, et al (2018)

Altered Gut Microbiota in Type 2 Diabetes: Just a Coincidence?.

Current diabetes reports, 18(10):98.

PURPOSE OF REVIEW: In the last decade many studies have suggested an association between the altered gut microbiota and multiple systemic diseases including diabetes. In this review, we will discuss potential pathophysiological mechanisms, the latest findings regarding the mechanisms linking gut dysbiosis and type 2 diabetes (T2D), and the results obtained with experimental modulation of microbiota.

RECENT FINDINGS: In T2D, gut dysbiosis contributes to onset and maintenance of insulin resistance. Different strategies that reduce dysbiosis can improve glycemic control. Evidence in animals and humans reveals differences between the gut microbial composition in healthy individuals and those with T2D. Changes in the intestinal ecosystem could cause inflammation, alter intestinal permeability, and modulate metabolism of bile acids, short-chain fatty acids and metabolites that act synergistically on metabolic regulation systems contributing to insulin resistance. Interventions that restore equilibrium in the gut appear to have beneficial effects and improve glycemic control. Future research should examine in detail and in larger studies other possible pathophysiological mechanisms to identify specific pathways modulated by microbiota modulation and identify new potential therapeutic targets.

RevDate: 2019-09-05

Martínez JV, Raush A, Efrón ED, et al (2019)

[Refractory colitis by Clostridium difficile treated with fecal microbiota transplant].

Medicina, 79(4):291-294.

Clostridium difficile infection is an increasingly recognized cause of diarrhea in inpatients, frequently associated to high mortality. Vancomycin is the treatment of choice for all Clostridium difficile- associated diarrheas, with different degrees of severity. However, some patients develop refractory forms to that treatment and there are no alternative antibiotic schemes recommended for these cases. Fecal microbiota transplantation has been shown to be successful in a series of cases of severe diarrhea associated with this organism. We present a case of refractory C. difficile infection successfully treated with fecal microbiota transplantation.

RevDate: 2019-09-04

Mishima Y, RB Sartor (2019)

Manipulating resident microbiota to enhance regulatory immune function to treat inflammatory bowel diseases.

Journal of gastroenterology pii:10.1007/s00535-019-01618-1 [Epub ahead of print].

Altered intestinal microbial composition (dysbiosis) and metabolic products activate aggressive mucosal immune responses that mediate inflammatory bowel diseases (IBD). This dysbiosis impairs the function of regulatory immune cells, which normally promote mucosal homeostasis. Normalizing and maintaining regulatory immune cell function by correcting dysbiosis provides a promising approach to treat IBD patients. However, existing microbe-targeted therapies, including antibiotics, prebiotics, probiotics, and fecal microbial transplantation, provide variable outcomes that are not optimal for current clinical application. This review discusses recent progress in understanding the dysbiosis of IBD and the basis for therapeutic restoration of homeostatic immune function by manipulating an individual patient's microbiota composition and function. We believe that identifying more precise therapeutic targets and developing appropriate rapid diagnostic tools will guide more effective and safer microbe-based induction and maintenance treatments for IBD patients that can be applied in a personalized manner.

RevDate: 2019-09-02

Monaghan TM, Pučić-Baković M, Vučković F, et al (2019)

Decreased Complexity of Serum N-glycan Structures Associates with Successful Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection.

Gastroenterology pii:S0016-5085(19)41259-6 [Epub ahead of print].

RevDate: 2019-08-31

Tan X, S Johnson (2019)

Fecal Microbiota Transplantation (FMT) for C. difficile Infection, just say 'No'.

Anaerobe pii:S1075-9964(19)30152-0 [Epub ahead of print].

Despite lack of regulatory approval, fecal microbiota transplantation (FMT) is widely performed to manage C. difficile infection (CDI), particularly recurrent CDI. Herein, we critically review the available randomized controlled trials of FMT and address the following questions: Is FMT better than drug management of recurrent CDI?; Is FMT treatment per se or adjunctive treatment to antibiotics for CDI?; and, Is FMT safe? Finally, we elaborate non-FMT options for the management of recurrent CDI. Although promising, FMT should be reserved for patients who have failed appropriate antibiotic management of recurrent CDI.

RevDate: 2019-08-31

Kim MS, Kim Y, Choi H, et al (2019)

Transfer of a healthy microbiota reduces amyloid and tau pathology in an Alzheimer's disease animal model.

Gut pii:gutjnl-2018-317431 [Epub ahead of print].

OBJECTIVE: Cerebral amyloidosis and severe tauopathy in the brain are key pathological features of Alzheimer's disease (AD). Despite a strong influence of the intestinal microbiota on AD, the causal relationship between the gut microbiota and AD pathophysiology is still elusive.

DESIGN: Using a recently developed AD-like pathology with amyloid and neurofibrillary tangles (ADLPAPT) transgenic mouse model of AD, which shows amyloid plaques, neurofibrillary tangles and reactive gliosis in their brains along with memory deficits, we examined the impact of the gut microbiota on AD pathogenesis.

RESULTS: Composition of the gut microbiota in ADLPAPT mice differed from that of healthy wild-type (WT) mice. Besides, ADLPAPT mice showed a loss of epithelial barrier integrity and chronic intestinal and systemic inflammation. Both frequent transfer and transplantation of the faecal microbiota from WT mice into ADLPAPT mice ameliorated the formation of amyloid β plaques and neurofibrillary tangles, glial reactivity and cognitive impairment. Additionally, the faecal microbiota transfer reversed abnormalities in the colonic expression of genes related to intestinal macrophage activity and the circulating blood inflammatory monocytes in the ADLPAPT recipient mice.

CONCLUSION: These results indicate that microbiota-mediated intestinal and systemic immune aberrations contribute to the pathogenesis of AD in ADLPAPT mice, providing new insights into the relationship between the gut (colonic gene expression, gut permeability), blood (blood immune cell population) and brain (pathology) axis and AD (memory deficits). Thus, restoring gut microbial homeostasis may have beneficial effects on AD treatment.

RevDate: 2019-08-30

Yoon YK, Suh JW, Kang EJ, et al (2019)

Efficacy and safety of fecal microbiota transplantation for decolonization of intestinal multidrug-resistant microorganism carriage: Beyond Clostridioides difficile infection.

Annals of medicine [Epub ahead of print].

Persistent reservoirs of multidrug-resistant microorganisms (MDRO) that are prevalent in hospital settings and communities can lead to the spread of MDRO. Currently, there are no effective decolonization strategies, especially non-pharmacological strategies without antibiotic regimens. Our aim was to evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for the eradication of MDRO. A systematic literature search was performed to identify studies on the use of FMT for the decolonization of MDRO. PubMed, EMBASE, Web of Science, and Cochrane Library were searched from inception through January 2019. Of the 1,395 articles identified, 20 studies met the inclusion and exclusion criteria. Overall, the efficacy of FMT for the eradication of each MDRO was 70.3% (102/146) in 121 patients from the 20 articles. The efficacy rates were 68.2% (30/44) for gram-positive bacteria and 70.6% (72/102) for gram-negative bacteria. Minor adverse events, including vomiting, diarrhea, abdominal pain, and ileus, were reported in patients who received FMT. FMT could be a promising strategy to eradicate MDRO in patients. Further studies are needed to confirm these findings and establish a comprehensive FMT protocol for standardized treatment. Key messages: The development of new antibiotics lags behind the emergence of multidrug-resistant microorganisms (MDRO). New strategies are needed. Theoretically, fecal microbiota transplantation (FMT) might recover the diversity and function of commensal microbiota from dysbiosis in MDRO carriers and help restore colonization resistance to pathogens. A literature review indicated that FMT could be a promising strategy to eradicate MDRO in patients.

RevDate: 2019-09-01

Zhou Y, Xu H, Huang H, et al (2019)

Are There Potential Applications of Fecal Microbiota Transplantation beyond Intestinal Disorders?.

BioMed research international, 2019:3469754.

Intestinal microbial dysbiosis is associated with various intestinal and extraintestinal disorders. Fecal microbiota transplantation (FMT), a type of fecal bacteriotherapy, is considered an effective therapeutic option for recurrent Clostridium difficile infection (rCDI) and also has important value in other intestinal diseases including irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). The purpose of this review is to discuss promising therapeutic value in extraintestinal diseases associated with gut microbial dysbiosis, including liver, metabolic, chronic kidney, neuropsychiatric, allergic, autoimmune, and hematological diseases as well as tumors.

RevDate: 2019-08-29

Liu Z, Li N, Fang H, et al (2019)

Enteric dysbiosis is associated with sepsis in patients.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology [Epub ahead of print].

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to microbial infection. For decades, the potential role of gut microbiota in sepsis pathogenesis has been revealed. However, the systemic and functional link between gut microbiota and sepsis has remained unexplored. To address this gap in knowledge, we carried out systematic analyses on clinical stool samples from patients with sepsis, including 16S rDNA sequencing, metabolomics, and metaproteomics analyses. In addition, we performed fecal microbiota transplantation from human to mice to validate the roles of gut microbiota on sepsis progression. We found that the composition of gut microbiota was significantly disrupted in patients with sepsis compared with healthy individuals. Besides, the microbial functions were significantly altered in septic feces as identified by metabolomics and metaproteomics analyses. Interestingly, mice that received septic feces exhibited more severe hepatic inflammation and injury than mice that received healthy feces after cecal ligation and puncture. Finally, several strains of intestinal microbiota and microbial metabolites were corelated with serum total bilirubin levels in patients with sepsis. Taken together, our data indicated that sepsis development is associated with the disruption of gut microbiota at both compositional and functional levels, and such enteric dysbiosis could promote organ inflammation and injury during sepsis.-Liu, Z., Li, N., Fang, H., Chen, X., Guo, Y., Gong, S., Niu, M., Zhou, H., Jiang, Y., Chang, P., Chen, P. Enteric dysbiosis is associated with sepsis in patients.

RevDate: 2019-09-05

Zhong S, Zeng J, Deng Z, et al (2019)

Fecal microbiota transplantation for refractory diarrhea in immunocompromised diseases: a pediatric case report.

Italian journal of pediatrics, 45(1):116 pii:10.1186/s13052-019-0708-9.

BACKGROUND: Immunocompromised (IC) patients have an increased risk of refractory diarrhea. Fecal microbiota transplantation (FMT) is a safe and effective therapy for infection-related diarrhea which are mainly mediated by the loss of the microbial colonization, although there is concern that IC patients may be at higher risk of infectious complications related to FMT. And reports of FMT in IC children are limited.

CASE PRESENTATION: We describe two cases of FMT in IC children with refractory diarrhea. One IC child had polyendocrinopathy, enteropathy, X-linked syndrome and the other child had graft-versus-host disease. Both of the children had a long course of diarrhea and no response to traditional treatment. FMT was performed on both patients via nasojejunal tubes under guidance of gastroduodenoscopy. After FMT, the patients achieved remission of symptoms and neither of them had related infectious complications. Microbiota analysis showed that FMT resulted in reconstruction of a diverse microbiota.

CONCLUSIONS: Use of FMT is safe and effective in treatment of refractory diarrhea in IC children with a damaged microbiota.

RevDate: 2019-08-26

Brüssow H (2019)

Problems with the concept of gut microbiota dysbiosis.

Microbial biotechnology [Epub ahead of print].

The human microbiome research is with the notable exception of fecal transplantation still mostly in a descriptive phase. Part of the difficulty for translating research into medical interventions is due to the large compositional complexity of the microbiome resulting in datasets that need sophisticated statistical methods for their analysis and do not lend to industrial applications. Another part of the difficulty might be due to logical flaws in terminology particularly concerning 'dysbiosis' that avoids circular conclusions and is based on sound ecological and evolutionary reasoning. Many case-control studies are underpowered necessitating more meta-analyses that sort out consistent from spurious dysbiosis-disease associations. We also need for the microbiome a transition from statistical associations to causal relationships with diseases that fulfil a set of modified Koch's postulates for commensals. Disturbingly, the most sophisticated statistical analyses explain only a small percentage of the variance in the microbiome. Microbe-microbe interactions irrelevant to the host and stochastic processes might play a greater role than anticipated. To satisfy the concept of Karl Popper about conjectures and refutations in the scientific process, we should also conduct more experiments that try to refute the role of the commensal gut microbiota for human health and disease.

RevDate: 2019-08-25

Hasan N, H Yang (2019)

Factors affecting the composition of the gut microbiota, and its modulation.

PeerJ, 7:e7502 pii:7502.

Gut microbiota have important functions in the body, and imbalances in the composition and diversity of those microbiota can cause several diseases. The host fosters favorable microbiota by releasing specific factors, such as microRNAs, and nonspecific factors, such as antimicrobial peptides, mucus and immunoglobulin A that encourage the growth of specific types of bacteria and inhibit the growth of others. Diet, antibiotics, and age can change gut microbiota, and many studies have shown the relationship between disorders of the microbiota and several diseases and reported some ways to modulate that balance. In this review, we highlight how the host shapes its gut microbiota via specific and nonspecific factors, how environmental and nutritional factors affect it, and how to modulate it using prebiotics, probiotics, and fecal microbiota transplantation.

RevDate: 2019-08-29

Zhang Y, Huang R, Cheng M, et al (2019)

Gut microbiota from NLRP3-deficient mice ameliorates depressive-like behaviors by regulating astrocyte dysfunction via circHIPK2.

Microbiome, 7(1):116 pii:10.1186/s40168-019-0733-3.

BACKGROUND: Inflammasomes have been found to interact with the gut microbiota, and this effect is associated with depression, but the mechanisms underlying this interaction have not been elucidated in detail.

RESULTS: The locomotor activity of NLRP3 KO mice was significantly greater than that of their WT littermates, while cohousing and transplantation of the NLRP3 KO gut microbiota avoid the effects of NLRP3 KO on the general locomotor activity at baseline. Meanwhile, transplantation of the NLRP3 KO microbiota alleviated the CUS-induced depressive-like behaviors. The compositions of the gut microbiota in NLRP3 KO mice and WT mice were significantly different in terms of the relative abundance of Firmicutes, Proteobacteria, and Bacteroidetes. Fecal microbiota transplantation (FMT) from NLRP3 KO mice significantly ameliorated the depressive-like behavior induced by chronic unpredictable stress (CUS) in recipient mice. Given the correlation between circular RNA HIPK2 (circHIPK2) and depression and the observation that the level of circHIPK2 expression was significantly increased in CUS-treated mice compared with that in the control group, further experiments were performed. FMT significantly ameliorated astrocyte dysfunction in recipient mice treated with CUS via inhibition of circHIPK2 expression.

CONCLUSIONS: Our study illustrates the involvement of the gut microbiota-circHIPK2-astrocyte axis in depression, providing translational evidence that transplantation of the gut microbiota from NLRP3 KO mice may serve as a novel therapeutic strategy for depression.

RevDate: 2019-08-27

Chang CS, CY Kao (2019)

Current understanding of the gut microbiota shaping mechanisms.

Journal of biomedical science, 26(1):59 pii:10.1186/s12929-019-0554-5.

Increasing evidences have shown strong associations between gut microbiota and many human diseases, and understanding the dynamic crosstalks of host-microbe interaction in the gut has become necessary for the detection, prevention, or therapy of diseases. Many reports have showed that diet, nutrient, pharmacologic factors and many other stimuli play dominant roles in the modulation of gut microbial compositions. However, it is inappropriate to neglect the impact of host factors on shaping the gut microbiota. In this review, we highlighted the current findings of the host factors that could modulate the gut microbiota. Particularly the epithelium-associated factors, including the innate immune sensors, anti-microbial peptides, mucus barrier, secretory IgAs, epithelial microvilli, epithelial tight junctions, epithelium metabolism, oxygen barrier, and even the microRNAs are discussed in the context of the microbiota shaping. With these shaping factors, the gut epithelial cells could select the residing microbes and affect the microbial composition. This knowledge not only could provide the opportunities to better control many diseases, but may also be used for predicting the success of fecal microbiota transplantation clinically.

RevDate: 2019-08-22
CmpDate: 2019-08-22

Guery B, Galperine T, F Barbut (2019)

Clostridioides difficile: diagnosis and treatments.

BMJ (Clinical research ed.), 366:l4609.

Clostridioides difficile (formerly Clostridium) is a major cause of healthcare associated diarrhea, and is increasingly present in the community. Historically, C difficile infection was considered easy to diagnose and treat. Over the past two decades, however, diagnostic techniques have changed in line with a greater understanding of the physiopathology of C difficile infection and the use of new therapeutic molecules. The evolution of diagnosis showed there was an important under- and misdiagnosis of C difficile infection, emphasizing the importance of algorithms recommended by European and North American infectious diseases societies to obtain a reliable diagnosis. Previously, metronidazole was considered the reference drug to treat C difficile infection, but more recently vancomycin and other newer drugs are shown to have higher cure rates. Recurrence of infection represents a key parameter in the evaluation of new drugs, and the challenge is to target the right population with the adapted therapeutic molecule. In multiple recurrences, fecal microbiota transplantation is recommended. New approaches, including antibodies, vaccines, and new molecules are already available or in the pipeline, but more data are needed to support the inclusion of these in practice guidelines. This review aims to provide a baseline for clinicians to understand and stratify their choice in the diagnosis and treatment of C difficile infection based on the most recent data available.

RevDate: 2019-09-03

Chen R, Xu Y, Wu P, et al (2019)

Transplantation of fecal microbiota rich in short chain fatty acids and butyric acid treat cerebral ischemic stroke by regulating gut microbiota.

Pharmacological research, 148:104403 pii:S1043-6618(19)30911-9 [Epub ahead of print].

The gut microbiota and its short chain fatty acid (SCFA) metabolites have been established to play an important protective role against neurodegenerative diseases. Our previous study demonstrated that cerebral ischemic stroke triggers dysfunctional gut microbiota and increased intestinal permeability. In this study, we aimed to clarify the mechanism by which gut microbiota and SCFAs can treat cerebral ischemic stroke in rat middle cerebral artery occlusion models and use the information to develop new therapies. Our results show that oral administration of non-absorbable antibiotics reduced neurological impairment and the cerebral infarct volume, relieved cerebral edemas, and decreased blood lipid levels by altering the gut microbiota. We also found that ischemic stroke decreased intestinal levels of SCFAs. And that transplanting fecal microbiota rich in these metabolites was an effective means of treating the condition. Compared with other SCFAs, butyric acid showed the highest negative correlation with ischemic stroke. Supplementation with butyric acid treated models of ischemic stroke effectively by remodeling the gut microbiota, enriching the beneficial Lactobacillus, and repairing the leaky gut. In conclusion, interfering with the gut microbiota by transplanting fecal bacteria rich in SCFAs and supplementing with butyric acid were found to be effective treatments for cerebral ischemic stroke.

RevDate: 2019-08-16

Mouries J, Brescia P, Silvestri A, et al (2019)

Microbiota-driven gut vascular barrier disruption is a prerequisite for non-alcoholic steatohepatitis development.

Journal of hepatology pii:S0168-8278(19)30471-4 [Epub ahead of print].

BACKGROUND AND AIMS: Fatty liver disease, including nonalcoholic fatty liver (NAFLD) and steatohepatitis (NASH), has been associated with increased intestinal barrier permeability and translocation of bacteria or bacterial products into the blood circulation. In this study we aim to unravel the role of both intestinal barriers integrity and microbiota in NAFDL/NASH development.

METHODS: C57BL/6J mice were fed with High Fat Diet (HFD) or Methionine Choline Deficient Diet for one week or longer to recapitulate NASH disease aspects (steatosis, inflammation, insulin resistance). Genetic and pharmacological strategies have been used to modulate the intestinal barriers integrity.

RESULTS: We show that disruption of intestinal epithelial barrier and gut vascular barrier (GVB) are early events in NASH pathogenesis. Mice fed a HFD for only one week undergo a diet-induced dysbiosis that drives GVB damage and bacteria translocation into the liver. Fecal microbiota transplantation from HFD-fed mice into specific pathogen-free recipients induces GVB damage and epidydimal adipose tissue enlargement. GVB disruption depends on interference with the WNT/β-catenin signaling pathway, as shown by genetic intervention driving β-catenin activation only in endothelial cells, preventing GVB disruption and NASH development. The bile acid analogue and farnesoid X receptor agonist obeticholic acid drives β-catenin activation in endothelial cells. Accordingly, pharmacologic intervention with OCA protects against GVB disruption, both as preventive and therapeutic agent. Importantly, we found upregulation of the GVB leakage marker in the colon of NASH patients.

CONCLUSIONS: We have identified a new player in NASH development, the GVB, whose damage leads to bacteria or bacterial product translocation into the blood circulation. Treatment aimed at restoring β-catenin activation in endothelial cells, such as administration of OCA, protects against GVB damage and NASH development.

LAY SUMMARY: Fatty liver disease incidence is reaching epidemic in USA, with more than 30% of adults having NAFLD (nonalcoholic fatty liver disease). NAFLD can develop into NASH (steatohepatitis), a more severe stage, that can ultimately turn into cirrhosis and hepatocellularcarcinoma. There is a known link between increased intestinal permeability and the development of the disease, however there is no clear description of the initiation of NASH, i.e. if it is a cause or a consequence of NASH. Here, we demonstrate for the first time that high fat diet induces changes in the microbiota, that will in turn disrupt the intestinal barrier. Indeed, there exist two layers of barrier that are sequentially disrupted when microbiota changes following high fat diet consumption. This disruption allows bacteria from the intestine to reach the blood stream and disseminate to the liver fostering the development of a fatty liver. When using a genetically modified mouse model, or a drug (OCA) that protects against barrier disruption, there is no development of the disease. This clearly shows that barrier disruption is a prerequisite for the disease to develop. Finally, we also found indication of barrier disruption in human samples from NASH patients, supporting the idea of a general mechanism. Altogether, these data clearly decipher the very first steps of fatty liver disease onset, and lead the way for a treatment using OCA to block barrier disruption.

RevDate: 2019-08-15

Rosenbaum JT (2019)

Just another crappy commentary: the future of fecal microbiota transplantation.

Expert review of clinical immunology [Epub ahead of print].

RevDate: 2019-08-15

Khan I, Ullah N, Zha L, et al (2019)

Alteration of Gut Microbiota in Inflammatory Bowel Disease (IBD): Cause or Consequence? IBD Treatment Targeting the Gut Microbiome.

Pathogens (Basel, Switzerland), 8(3): pii:pathogens8030126.

Inflammatory bowel disease (IBD) is a chronic complex inflammatory gut pathological condition, examples of which include Crohn's disease (CD) and ulcerative colitis (UC), which is associated with significant morbidity. Although the etiology of IBD is unknown, gut microbiota alteration (dysbiosis) is considered a novel factor involved in the pathogenesis of IBD. The gut microbiota acts as a metabolic organ and contributes to human health by performing various physiological functions; deviation in the gut flora composition is involved in various disease pathologies, including IBD. This review aims to summarize the current knowledge of gut microbiota alteration in IBD and how this contributes to intestinal inflammation, as well as explore the potential role of gut microbiota-based treatment approaches for the prevention and treatment of IBD. The current literature has clearly demonstrated a perturbation of the gut microbiota in IBD patients and mice colitis models, but a clear causal link of cause and effect has not yet been presented. In addition, gut microbiota-based therapeutic approaches have also shown good evidence of their effects in the amelioration of colitis in animal models (mice) and IBD patients, which indicates that gut flora might be a new promising therapeutic target for the treatment of IBD. However, insufficient data and confusing results from previous studies have led to a failure to define a core microbiome associated with IBD and the hidden mechanism of pathogenesis, which suggests that well-designed randomized control trials and mouse models are required for further research. In addition, a better understanding of this ecosystem will also determine the role of prebiotics and probiotics as therapeutic agents in the management of IBD.

RevDate: 2019-08-14

Yang J, H Yang (2019)

Non-antibiotic therapy for Clostridioides difficile infection: A review.

Critical reviews in clinical laboratory sciences [Epub ahead of print].

Clostridioides difficile infection (CDI) is a common infectious disease that is mainly caused by antibiotics. Antibiotic therapy is still the dominant treatment for CDI, although it is accompanied by side effects. Probiotics, fecal microbiota transplantation (FMT), engineered microorganisms, bacteriophages, diet, natural active substances, nanoparticles and compounds are examples of emerging non-antibiotic therapies that have received a great amount of attention. In this review, we collected data about different non-antibiotic therapies for CDI and provided a comprehensive analysis and detailed comparison of these therapies. The mechanism of action, therapeutic efficacy, and the strengths and weaknesses of these non-antibiotic therapies have been investigated to provide a basis for the reasonable alternative of non-antibiotic therapies for CDI. In summary, probiotics and FMT are currently the best choice for non-antibiotic therapy for CDI.

RevDate: 2019-09-02

Sood A, Singh A, Mahajan R, et al (2019)

Acceptability, tolerability, and safety of fecal microbiota transplantation in patients with active ulcerative colitis (AT&S Study).

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

BACKGROUND AND AIM: Fecal microbiota transplantation (FMT) targets gut microbiome dysbiosis and is an emerging therapy for ulcerative colitis (UC). Although initial results with FMT in patients with active UC are encouraging, data regarding its acceptability, tolerability, and safety are scant.

METHODS: A retrospective analysis of patients with active UC (Mayo clinic score ≥ 4), who received multisession FMT (at weeks 0, 2, 6, 10, 14, 18, and 22) via colonoscopy between June 2016 and June 2018, was performed. Patient acceptability, tolerability, and immediate and long-term safety of the therapy were assessed.

RESULTS: Of the 129 patients with active UC who were offered FMT, 101 patients consented, giving acceptability of 78.3%. Fecal slurry retention time improved with each session (3.27 ± 1.06 h for the first session vs 5.12 ± 0.5 h for the seventh session). Abdominal discomfort, flatulence, abdominal distension, borborygmi, and low-grade fever (30.8%, 15.9%, 9.8%, 7.9%, and 7.6%, respectively) were the most common post-procedural short-term adverse events. Long-term adverse events included new-onset urticaria (n = 2, 4.3%), arthritis/arthralgia (n = 3, 6.5%), depression (n = 1, 2.2%), partial sensorineural hearing loss (n = 1, 2.2%), and allergic bronchitis (n = 1, 2.2%). Thirteen (12.9%) patients dropped out because of adverse events.

CONCLUSION: Fecal microbiota transplantation appears to be a safe and well-tolerated procedure, with good acceptability in patients with active UC.

RevDate: 2019-08-15

Gargiullo L, Del Chierico F, D'Argenio P, et al (2019)

Gut Microbiota Modulation for Multidrug-Resistant Organism Decolonization: Present and Future Perspectives.

Frontiers in microbiology, 10:1704.

The emergence of antimicrobial resistance (AMR) is of great concern to global public health. Treatment of multi-drug resistant (MDR) infections is a major clinical challenge: the increase in antibiotic resistance leads to a greater risk of therapeutic failure, relapses, longer hospitalizations, and worse clinical outcomes. Currently, there are no validated treatments for many MDR or pandrug-resistant (PDR) infections, and preventing the spread of these pathogens through hospital infection control procedures and antimicrobial stewardship programs is often the only tool available to healthcare providers. Therefore, new solutions to control the colonization of MDR pathogens are urgently needed. In this narrative review, we discuss current knowledge of microbiota-mediated mechanisms of AMR and strategies for MDR colonization control. We focus particularly on fecal microbiota transplantation for MDR intestinal decolonization and report updated literature on its current clinical use.

RevDate: 2019-08-09

Riquelme E, Zhang Y, Zhang L, et al (2019)

Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes.

Cell, 178(4):795-806.e12.

Most patients diagnosed with resected pancreatic adenocarcinoma (PDAC) survive less than 5 years, but a minor subset survives longer. Here, we dissect the role of the tumor microbiota and the immune system in influencing long-term survival. Using 16S rRNA gene sequencing, we analyzed the tumor microbiome composition in PDAC patients with short-term survival (STS) and long-term survival (LTS). We found higher alpha-diversity in the tumor microbiome of LTS patients and identified an intra-tumoral microbiome signature (Pseudoxanthomonas-Streptomyces-Saccharopolyspora-Bacillus clausii) highly predictive of long-term survivorship in both discovery and validation cohorts. Through human-into-mice fecal microbiota transplantation (FMT) experiments from STS, LTS, or control donors, we were able to differentially modulate the tumor microbiome and affect tumor growth as well as tumor immune infiltration. Our study demonstrates that PDAC microbiome composition, which cross-talks to the gut microbiome, influences the host immune response and natural history of the disease.

RevDate: 2019-08-11

Zhou GF, Jiang YH, Ma DF, et al (2019)

Xiao-Qing-Long Tang Prevents Cardiomyocyte Hypertrophy, Fibrosis, and the Development of Heart Failure with Preserved Ejection Faction in Rats by Modulating the Composition of the Gut Microbiota.

BioMed research international, 2019:9637479.

Background: Changes in the gut microbiota are associated with cardiovascular disease progression. Xiao-Qing-Long Tang (XQLT), a traditional herbal formula, has an anti-inflammatory effect and regulates the steady state of the immune system, which is also associated with the progression of heart failure with preserved ejection faction (HFpEF). In this study, we investigated whether XQLT could contribute to prevent the development of HFpEF and whether the modulation of the gut microbiota by this herbal formula could be involved in such effect.

Methods: The gut microbiota, SCFAs, the histology/function of the heart, and systolic blood pressure were examined to evaluate the effect of XQLT on the gut microbiota and the progression of HFpEF after oral administration of XQLT to model rats. Furthermore, we evaluated, through fecal microbiota transplantation experiments, whether the favorable effects of XQLT could be mediated by the gut microbiota.

Results: Oral administration of XQLT contributed to the reduction of elevated blood pressure, inflammation, and compensatory hypertrophy, features that are associated with the progression of HFpEF. The gut microbiota composition, SCFA levels, and intestinal mucosal histology were improved after treatment with XQLT. Moreover, fecal transfer from XQLT-treated rats was sufficient to prevent the progression of HFpEF.

Conclusions: These data suggested that XQLT prevented the development of HFpEF in model rats by regulating the composition of the gut microbiota.

RevDate: 2019-08-09

El-Salhy M, Hatlebakk JG, T Hausken (2019)

Diet in Irritable Bowel Syndrome (IBS): Interaction with Gut Microbiota and Gut Hormones.

Nutrients, 11(8): pii:nu11081824.

Diet plays an important role not only in the pathophysiology of irritable bowel syndrome (IBS), but also as a tool that improves symptoms and quality of life. The effects of diet seem to be a result of an interaction with the gut bacteria and the gut endocrine cells. The density of gut endocrine cells is low in IBS patients, and it is believed that this abnormality is the direct cause of the symptoms seen in IBS patients. The low density of gut endocrine cells is probably caused by a low number of stem cells and low differentiation progeny toward endocrine cells. A low fermentable oligo-, di-, monosaccharide, and polyol (FODMAP) diet and fecal microbiota transplantation (FMT) restore the gut endocrine cells to the level of healthy subjects. It has been suggested that our diet acts as a prebiotic that favors the growth of a certain types of bacteria. Diet also acts as a substrate for gut bacteria fermentation, which results in several by-products. These by-products might act on the stem cells in such a way that the gut stem cells decrease, and consequently, endocrine cell numbers decrease. Changing to a low-FODMAP diet or changing the gut bacteria through FMT improves IBS symptoms and restores the density of endocrine cells.

RevDate: 2019-08-11

Muscogiuri G, Cantone E, Cassarano S, et al (2019)

Gut microbiota: a new path to treat obesity.

International journal of obesity supplements, 9(1):10-19.

Obesity is a multifactorial disease resulting in excessive accumulation of adipose tissue. Over the last decade, growing evidence has identified the gut microbiota as a potential factor in the pathophysiology of both obesity and the related metabolic disorders. The gut microbiota is known to protect gastrointestinal mucosa permeability and to regulate the fermentation and absorption of dietary polysaccharides, perhaps explaining its importance in the regulation of fat accumulation and the resultant obesity. The proposed mechanisms by which the gut microbiota could contribute to the pathogenesis of obesity and the related metabolic diseases include: (a) a high abundance of bacteria that ferment carbohydrates, leading to increased rates of short-chain fatty acid (SCFA) biosynthesis, providing an extra source of energy for the host, that is eventually stored as lipids or glucose; (b) increased intestinal permeability to bacterial lipopolysaccharides (LPS), resulting in elevated systemic LPS levels that aggravate low-grade inflammation and insulin resistance; (c) increased activity of the gut endocannabinoid system. Fecal transplantation studies in germ-free mice have provided crucial insights into the potential causative role of the gut microbiota in the development of obesity and obesity-related disorders. Diet +/- bariatric surgery have been reported to modulate the gut microbiota, leading to lean host phenotype body composition. This review aims to report clinical evidence for a link of the gut microbiota with human obesity and obesity-related diseases, to provide molecular insights into these associations, and to address the effect of diet and bariatric surgery on the gut microbiota, including colonic microbiota, as a potential mechanism for promoting weight loss.

RevDate: 2019-08-08

Zhu F, Guo R, Wang W, et al (2019)

Transplantation of microbiota from drug-free patients with schizophrenia causes schizophrenia-like abnormal behaviors and dysregulated kynurenine metabolism in mice.

Molecular psychiatry pii:10.1038/s41380-019-0475-4 [Epub ahead of print].

Accumulating evidence suggests that gut microbiota plays a role in the pathogenesis of schizophrenia via the microbiota-gut-brain axis. This study sought to investigate whether transplantation of fecal microbiota from drug-free patients with schizophrenia into specific pathogen-free mice could cause schizophrenia-like behavioral abnormalities. The results revealed that transplantation of fecal microbiota from schizophrenic patients into antibiotic-treated mice caused behavioral abnormalities such as psychomotor hyperactivity, impaired learning and memory in the recipient animals. These mice also showed elevation of the kynurenine-kynurenic acid pathway of tryptophan degradation in both periphery and brain, as well as increased basal extracellular dopamine in prefrontal cortex and 5-hydroxytryptamine in hippocampus, compared with their counterparts receiving feces from healthy controls. Furthermore, colonic luminal filtrates from the mice transplanted with patients' fecal microbiota increased both kynurenic acid synthesis and kynurenine aminotransferase II activity in cultured hepatocytes and forebrain cortical slices. Sixty species of donor-derived bacteria showed significant difference between the mice colonized with the patients' and the controls' fecal microbiota, highlighting 78 differentially enriched functional modules including tryptophan biosynthesis function. In conclusion, our study suggests that the abnormalities in the composition of gut microbiota contribute to the pathogenesis of schizophrenia partially through the manipulation of tryptophan-kynurenine metabolism.

RevDate: 2019-08-07

Berbers RM, Franken IA, HL Leavis (2019)

Immunoglobulin A and microbiota in primary immunodeficiency diseases.

Current opinion in allergy and clinical immunology [Epub ahead of print].

PURPOSE OF REVIEW: With the emergence of the microbiota as a potential driver of host inflammation, the role of iIgA is becoming increasingly important. This review discusses the current evidence regarding the effects of clinical IgA deficiency on the microbiota, and the possible role of microbial dysbiosis in driving inflammation in PID patients.

RECENT FINDINGS: The gut microbiota has been investigated in selective IgA deficiency and common variable immunodeficiency, revealing an important role for IgA in maintaining gut microbiota homeostasis, with disparate effects of IgA on symbionts and pathobionts. Although IgA deficiency is associated with microbial translocation and systemic inflammation, this may be partially compensated by adequate IgG and IgM induction in IgA deficiency but not in common variable immunodeficiency. Therapeutic strategies aimed at correction of the microbiota mostly focus on fecal microbiota transplantation. Whether this may reduce systemic inflammation in PID is currently unknown.

SUMMARY: Clinical IgA deficiency is associated with microbial dysbiosis and systemic inflammation. The evidence for microbiota-targeted therapies in PID is scarce, but indicates that IgA-based therapies may be beneficial, and that fecal microbiota transplantation is well tolerated in patients with antibody deficiency.

RevDate: 2019-08-08

Santiago M, Eysenbach L, Allegretti J, et al (2019)

Microbiome predictors of dysbiosis and VRE decolonization in patients with recurrent C. difficile infections in a multi-center retrospective study.

AIMS microbiology, 5(1):1-18 pii:microbiol-05-01-001.

The gastrointestinal microbiome is intrinsically linked to the spread of antibiotic resistance. Antibiotic treatment puts patients at risk for colonization by opportunistic pathogens like vancomycin resistant Enterococcus and Clostridioides difficile by destroying the colonization resistance provided by the commensal microbiota. Once colonized, the host is at a much higher risk for infection by that pathogen. Furthermore, we know that microbiome community differences are associated with disease states, but we do not have a good understanding of how we can use these changes to classify different patient populations. To that end, we have performed a multicenter retrospective analysis on patients who received fecal microbiota transplants to treat recurrent Clostridioides difficile infection. We performed 16S rRNA gene sequencing on fecal samples collected as part of this study and used these data to develop a microbiome disruption index. Our microbiome disruption index is a simple index that is predictive across cohorts, indications, and batch effects. We are able to classify pre-fecal transplant vs post-fecal transplant samples in patients with recurrent C. difficile infection, and we are able to predict, using previously-published data from a cohort of patients receiving hematopoietic stem cell transplants, which patients would go on to develop bloodstream infections. Finally, we also identified patients in this cohort that were initially colonized with vancomycin resistant Enterococcus and that 92% (11/12) were decolonized after the transplant, but the microbiome disruption index was unable to predict such decolonization. We, however, were able to compare the relative abundance of different taxa between the two groups, and we found that increased abundance of Enterobacteriaceae predicts whether patients were colonized with vancomycin resistant Enterococcus. This work is an early step towards a better understanding of how microbiome predictors can be used to help improve patient care and patient outcomes.

RevDate: 2019-08-09

Sun J, Xu J, Ling Y, et al (2019)

Fecal microbiota transplantation alleviated Alzheimer's disease-like pathogenesis in APP/PS1 transgenic mice.

Translational psychiatry, 9(1):189 pii:10.1038/s41398-019-0525-3.

Alzheimer's disease (AD) is the most common dementia in the elderly. Treatment for AD is still a difficult task in clinic. AD is associated with abnormal gut microbiota. However, little is known about the role of fecal microbiota transplantation (FMT) in AD. Here, we evaluated the efficacy of FMT for the treatment of AD. We used an APPswe/PS1dE9 transgenic (Tg) mouse model. Cognitive deficits, brain deposits of amyloid-β (Aβ) and phosphorylation of tau, synaptic plasticity as well as neuroinflammation were assessed. Gut microbiota and its metabolites short-chain fatty acids (SCFAs) were analyzed by 16S rRNA sequencing and 1H nuclear magnetic resonance (NMR). Our results showed that FMT treatment could improve cognitive deficits and reduce the brain deposition of amyloid-β (Aβ) in APPswe/PS1dE9 transgenic (Tg) mice. These improvements were accompanied by decreased phosphorylation of tau protein and the levels of Aβ40 and Aβ42. We observed an increases in synaptic plasticity in the Tg mice, showing that postsynaptic density protein 95 (PSD-95) and synapsin I expression were increased after FMT. We also observed the decrease of COX-2 and CD11b levels in Tg mice after FMT. We also found that FMT treatment reversed the changes of gut microbiota and SCFAs. Thus, FMT may be a potential therapeutic strategy for AD.

RevDate: 2019-08-08

Dhakal S, Wang L, Antony L, et al (2019)

Amish (Rural) vs. non-Amish (Urban) Infant Fecal Microbiotas Are Highly Diverse and Their Transplantation Lead to Differences in Mucosal Immune Maturation in a Humanized Germfree Piglet Model.

Frontiers in immunology, 10:1509.

The gut microbiome plays an important role in the immune system development, maintenance of normal health status, and in disease progression. In this study, we comparatively examined the fecal microbiomes of Amish (rural) and non-Amish (urban) infants and investigated how they could affect the mucosal immune maturation in germ-free piglets that were inoculated with the two types of infant fecal microbiota (IFM). Differences in microbiome diversity and structure were noted between the two types of fecal microbiotas. The fecal microbiota of the non-Amish (urban) infants had a greater relative abundance of Actinobacteria and Bacteroidetes phyla, while that of the Amish (rural) counterparts was dominated by Firmicutes. Amish infants had greater species richness compared with the non-Amish infants' microbiota. The fecal microbiotas of the Amish and the non-Amish infants were successfully transplanted into germ-free piglets, and the diversity and structure of the microbiota in the transplanted piglets remained similar at phylum level but not at the genus level. Principal coordinates analysis (PCoA) based on Weighted-UniFrac distance revealed distinct microbiota structure in the intestines of the transplanted piglets. Shotgun metagenomic analysis also revealed clear differences in functional diversity of fecal microbiome between Amish and non-Amish donors as well as microbiota transplanted piglets. Specific functional features were enriched in either of the microbiota transplanted piglet groups directly corresponding to the predominance of certain bacterial populations in their gut environment. Some of the colonized bacterial genera were correlated with the frequency of important lymphoid and myeloid immune cells in the ileal submucosa and mesenteric lymph nodes (MLN), both important for mucosal immune maturation. Overall, this study demonstrated that transplantation of diverse IFM into germ-free piglets largely recapitulates the differences in gut microbiota structure between rural (Amish) and urban (non-Amish) infants. Thus, fecal microbiota transplantation to germ-free piglets could be a useful large animal model system for elucidating the impact of gut microbiota on the mucosal immune system development. Future studies can focus on determining the additional advantages of the pig model over the rodent model.

RevDate: 2019-08-26
CmpDate: 2019-08-26

Allegretti JR, Mullish BH, Kelly C, et al (2019)

The evolution of the use of faecal microbiota transplantation and emerging therapeutic indications.

Lancet (London, England), 394(10196):420-431.

Developments in high-throughput microbial genomic sequencing and other systems biology techniques have given novel insight into the potential contribution of the gut microbiota to health and disease. As a result, an increasing number of diseases have been characterised by distinctive changes in the composition and functionality of the gut microbiota; however, whether such changes are cause, consequence, or incidental to the disease in question remains largely uncertain. Restoration of the gut microbiota to a premorbid state is a key novel therapeutic approach of interest, and faecal microbiota transplantation-the transfer of prescreened stool from healthy donors into the gastrointestinal tract of patients-is gaining increasing importance in both the clinical and research settings. At present, faecal microbiota transplantation is only recommended in the treatment of recurrent Clostridioides difficile infection, although a large number of trials are ongoing worldwide exploring other potential therapeutic indications.

RevDate: 2019-08-07

Ma Y, Xu X, Li M, et al (2019)

Gut microbiota promote the inflammatory response in the pathogenesis of systemic lupus erythematosus.

Molecular medicine (Cambridge, Mass.), 25(1):35 pii:10.1186/s10020-019-0102-5.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease whose onset and progression are affected by genetic and environmental factors. The purpose of this study is to identify the influence of gut microbiota in the pathogenesis of SLE, and to investigate the mechanism involved.

METHODS: Fecal microbiota from C57/BL6 mice and SLE prone mice were examined using next-generation sequencing (NGS). Germ free mice were given fecal microbiota transplantation (FMT), and their gut microbiome and gene expression in recipients' colons were examined by NGS. The anti-double stranded DNA (anti-dsDNA) antibodies in recipients were determined using an enzyme-linked immunosorbent assay (ELISA). The immune cell profiles of mice were analyzed by flow cytometry at the 3rd week after FMT, and the expression of genes associated with SLE after FMT was determined using quantitative real-time PCR (qRT-PCR).

RESULTS: The fecal microbiota of SLE mice had lower community richness and diversity than healthy mice. Fecal microbiota of recipient mice were similar to their donors. Fecal microbiome from SLE mice could lead to a significant increase of anti-dsDNA antibodies and promote the immune response in recipient mice. Our results also indicated that fecal microbiome from SLE mice resulted in significant changes in the distribution of immune cells and upregulated expression of certain lupus susceptibility genes.

CONCLUSIONS: SLE is associated with alterations of gut microbiota. Fecal microbiome from SLE mice can induce the production of anti-dsDNA antibodies in germ free mice and stimulate the inflammatory response, and alter the expression of SLE susceptibility genes in these mice.

RevDate: 2019-09-04

Shin JH, CA Warren (2019)

Prevention and treatment of recurrent Clostridioides difficile infection.

Current opinion in infectious diseases, 32(5):482-489.

PURPOSE OF REVIEW: Clostridioides difficile infection (CDI) is a significant burden on the health system, especially due to high recurrence rates. Since the beginning of the CDI epidemic in early 2000s, many strategies for combatting recurrence have been explored, with moderate success so far. This review will focus on the most recent developments in recurrent CDI prevention and treatment.

RECENT FINDINGS: There are two main mechanisms of CDI recurrence: alteration in microbiome and poor antibody response. Development of new antibiotics aims to minimize damage to the microbiome. Fecal transplant or other microbiome replacement therapies seek to replenish the missing elements in the microbiome. Fecal microbiota transplant is the most effective treatment for prevention of CDI recurrenceso far, but is difficult to standardize and regulate, leading to efforts to develop microbiome-derived therapeutics. A deficiency in developing antibodies to C. difficile toxins is another mechanism of recurrence. Active immunization using toxoid vaccines or passive immunization using mAbs address this aspect.

SUMMARY: There are promising new treatments for recurrent CDI in development. Fecal microbiota transplant remains the most effective therapy for multiply recurrent CDI. New antibiotics, microbiome-derived therapeutics, and immunologic therapies are in development.

RevDate: 2019-08-01

Yang Z, Bu C, Yuan W, et al (2019)

Fecal Microbiota Transplant via Endoscopic Delivering Through Small Intestine and Colon: No Difference for Crohn's Disease.

Digestive diseases and sciences pii:10.1007/s10620-019-05751-y [Epub ahead of print].

BACKGROUND AND AIMS: Crohn's disease (CD) is a chronic inflammatory bowel disorder associated with intestinal dysbiosis. This study aimed to determine the efficacy and safety of different methods of fecal microbiota transplantation (FMT), a potential therapy for CD.

METHODS: Patients with CD were randomized to receive FMT by gastroscopy or colonoscopy; a second transplantation was performed 1 week later. Patients were assessed by clinical evaluation and serum testing (at weeks 1, 2, 4, 6, and 8) and endoscopy (8 weeks after transplantation). Fecal DNA was extracted and analyzed using the Illuminal sequencing platform.

RESULTS: Of the 27 patients included in the study, clinical remission was achieved in 18 (66.7%); no significant difference was seen between the two methods. 76.9% of gastroscopy group patients and 64.3% of colonoscopy group patients experienced mild adverse events during or shortly after treatment. Microbiota diversity analyses showed that, in comparison with the donors, patients had lower operational taxonomic units (OTU; 117 vs. 258, p < 0.05) and Shannon diversity index (2.05 vs. 3.46, p < 0.05). The CD patients showed a significant increase in OTU and Shannon diversity index 2 weeks after FMT. In comparison with the donors, CD patients had lower levels of Bacteroides, Eubacterium, faecalibacterium, and Roseburia, and higher levels of Clostridium, Cronobacter, Fusobacterium, and Streptococcus.

CONCLUSIONS: FMT was seen to be safe and effective in this cohort of patients with CD. No significant differences in clinical remission rate and adverse events were seen between the gastroscopy and colonoscopy groups. FMT was seen to increase the species richness in CD patients.

RevDate: 2019-08-04

Liu MT, Huang YJ, Zhang TY, et al (2019)

Lingguizhugan decoction attenuates diet-induced obesity and hepatosteatosis via gut microbiota.

World journal of gastroenterology, 25(27):3590-3606.

BACKGROUND: Obesity is a major risk factor for a variety of diseases such as diabetes, nonalcoholic fatty liver disease, and cardiovascular diseases. Restricting energy intake, or caloric restriction (CR), can reduce body weight and improve metabolic parameters in overweight or obese patients. We previously found that Lingguizhugan decoction (LZD) in combination with CR can effectively lower plasma lipid levels in patients with metabolic syndrome. However, the mechanism underlying CR and LZD treatment is still unclear.

AIM: To investigate whether CR and LZD improve metabolic parameters by modulating gut microbiota.

METHODS: We extracted the water-soluble components out of raw materials and dried as LZD extracts. Eight-week old male C57BL/6 mice were treated with a 3-d treatment regime that included 24 h-fasting followed by gavage of LZD extracts for 2 consecutive days, followed by a normal diet (ND) ad libitum for 16 wk. To test the effects of gut microbiota on diet-induced obesity, 8-wk old male C57BL/6 mice received fecal microbiota transplantation (FMT) from CR and LZD-treated mice every 3 d and were fed with high-fat diet (HFD) ad libitum for 16 wk. Control mice received either saline gavage or FMT from ND-fed mice receiving saline gavage as mentioned above. Body weight was monitored bi-weekly. Food consumption of each cage hosting five mice was recorded weekly. To monitor blood glucose, total cholesterol, and total triglycerides, blood samples were collected via submandibular bleeding after 6 h fasting. Oxygen consumption rate was monitored with metabolic cages. Feces were collected, and fecal DNA was extracted. Profiles of gut microbiota were mapped by metagenomic sequencing.

RESULTS: We found that CR and LZD treatment significantly reduced the body weight of mice fed with ND (28.71 ± 0.29 vs 28.05 ± 0.15, P < 0.05), but did not affect plasma total cholesterol or total triglyceride levels. We then transplanted the fecal microbiota collected from CR and LZD-treated mice under ND feeding to HFD-fed mice. Intriguingly, transplanting the mice with fecal microbiota from CR and LZD-treated mice potently reduced body weight (44.95 ± 1.02 vs 40.53 ± 0.97, P < 0.001). FMT also reduced HFD-induced hepatosteatosis, in addition to improved glycemic control. Mechanistic studies found that FMT increased OCR of the mice and suppressed the expression and protein abundance of lipogenic genes in the liver. Metagenomic analysis revealed that HFD drastically altered the profile of gut microbiota, and FMT modified the profile of the gut microbiota.

CONCLUSION: Our study suggests that CR and LZD improve metabolic parameters by modulating gut microbiota.

RevDate: 2019-08-06

Woodworth MH, Hayden MK, Young VB, et al (2019)

The Role of Fecal Microbiota Transplantation in Reducing Intestinal Colonization With Antibiotic-Resistant Organisms: The Current Landscape and Future Directions.

Open forum infectious diseases, 6(7):.

The intestinal tract is a recognized reservoir of antibiotic-resistant organisms (ARO), and a potential target for strategies to reduce ARO colonization. Microbiome therapies such as fecal microbiota transplantation (FMT) have been established as an effective treatment for recurrent Clostridioides difficile infection and may be an effective approach for reducing intestinal ARO colonization. In this article, we review the current published literature on the role of FMT for eradication of intestinal ARO colonization, review the potential benefit and limitations of the use of FMT in this setting, and outline a research agenda for the future study of FMT for intestinal ARO colonization.

RevDate: 2019-08-06

Wang X, Tsai T, Deng F, et al (2019)

Longitudinal investigation of the swine gut microbiome from birth to market reveals stage and growth performance associated bacteria.

Microbiome, 7(1):109 pii:10.1186/s40168-019-0721-7.

BACKGROUND: Despite recent advances in the understanding of the swine gut microbiome at different growth stages, a comprehensive longitudinal study of the lifetime (birth to market) dynamics of the swine gut microbiome is lacking.

RESULTS: To fill in this gap of knowledge, we repeatedly collected a total of 273 rectal swabs from 18 pigs during lactation (day (d) 0, 11, 20), nursery (d 27, 33, 41, 50, 61), growing (d 76, 90, 104, 116), and finishing (d 130, 146, 159, 174) stages. DNA was extracted and subjected to sequencing with an Illumina Miseq sequencer targeting the V4 region of the 16S rRNA gene. Sequences were analyzed with the Deblur algorithm in the QIIME2 package. A total of 19 phyla were detected in the lifetime pig gut microbiome with Firmicutes and Bacteroidetes being the most abundant. Alpha diversity including community richness (e.g., number of observed features) and diversity (e.g., Shannon index) showed an overall increasing trend. Distinct shifts in microbiome structure along different growth stages were observed. LEfSe analysis revealed 91 bacterial features that are stage-specific. To validate these discoveries, we performed fecal microbiota transplantation (FMT) by inoculating weanling pigs with mature fecal microbiota from a growing stage pig. Similar stage-specific patterns in microbiome diversity and structures were also observed in both the FMT pigs and their littermates. Although FMT remarkably increased growth performance, it did not change the overall swine gut microbiome. Only a few taxa including those associated with Streptococcus and Clostridiaceae were enriched in the FMT pigs. These data, together with several other lines of evidence, indicate potential roles these taxa play in promoting animal growth performance. Diet, especially crude fiber from corn, was a major factor shaping the swine gut microbiome. The priority effect, i.e., the order and timing of species arrival, was more evident in the solid feed stages.

CONCLUSIONS: The distinct stage-associated swine gut microbiome may be determined by the differences in diet and/or gut physiology at different growth stages. Our study provides insight into mechanisms governing gut microbiome succession and also underscores the importance of optimizing stage-specific probiotics aimed at improving animal health and production.


RJR Experience and Expertise


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.


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.


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.


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.


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.


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.


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.


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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E-mail: RJR8222@gmail.com

Collection of publications by R J Robbins

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

Research Gate page for R J Robbins

ResearchGate is a social networking site for scientists and researchers to share papers, ask and answer questions, and find collaborators. According to a study by Nature and an article in Times Higher Education , it is the largest academic social network in terms of active users.

Curriculum Vitae for R J Robbins

short personal version

Curriculum Vitae for R J Robbins

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RJR Picks from Around the Web (updated 11 MAY 2018 )