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Bibliography on: Fecal Transplantation

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ESP: PubMed Auto Bibliography 10 Dec 2018 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: 2018-12-06

Huang C, Yang X, Zeng B, et al (2018)

Proteomic analysis of olfactory bulb suggests CACNA1E as a promoter of CREB signaling in microbiota-induced depression.

Journal of proteomics pii:S1874-3919(18)30421-4 [Epub ahead of print].

Major depressive disorders impact approximately 17% of the population worldwide, whose high morbidity and considerable adversity have resulted in enormous social and economic burden. In addition, clinically depressed patients often show reduced volume of olfactory bulb (OB) and decreased olfactory sensitivity. Although mounting evidence conveyed that the gut microbiota may implicate the pathophysiology of major depressive disorder (MDD) via the microbe-gut-brain axis, knowledge about its distinctive molecular mechanism is rudimentary. Herein, iTRAQ coupled with LC-MS/MS was applied to compare the OB proteome between "pathological microbiota" and "healthy microbiota" germ-free mice. A set of 367 proteins were differentially identified in the OB, including 119 up-regulated and 248 down-regulated proteins compared with the levels in controls. A combined analysis with significantly changed OB proteins from CUMS depression model supported the role of CREB signaling, whose dysregulation is likely to disrupt the axonogenesis of OB under microbiota condition. With that, the down-regulated CACNA1E and its downstream proteins (CALM/ CaMKII/ CREB/ BDNF) in CREB pathway were validated by Western blot. Meanwhile, the canonical pathways involved Nuclear Receptor Signaling highlighted the fecal microbiota transplantation (FMT) model, which would be a new breakthrough for depressive research. These findings enrich the previous research achievements about the gut microbiota in psychiatric disorders, providing a creative insight into the intricate mechanisms of OB dysfunction in depression. SIGNIFICANCE: Emerging evidence has shown that gut microbiota can greatly influence brain functions and even behaviors. As one of the post-developmental neurogenesis areas for the adult brain, the OB is becoming increasingly important in the study of the pathogenesis of depression. Using an iTRAQ-based proteomics, we identified 367 altered proteins in the OB of fecal microbiota transplanted mouse, which provide a novel insight for further research of the "microbiota-gut-brain axis". In addition, combined analyses with the CUMS depression model and the validation of key proteins by Western blot may assist in the investigation of OB dysfunction in mental sickness.

RevDate: 2018-12-06

Al-Amer M, Abdeen Y, A Kaako (2018)

Bezlotoxumab Use as Adjunctive Therapy with the Third Fecal Microbiota Transplant in Refractory Recurrent Clostridium Difficile Colitis; A Case Report and Concise Literature Review.

Anaerobe pii:S1075-9964(18)30205-1 [Epub ahead of print].

Clostridium difficile is the most commonly reported pathogen to cause nosocomial infections in the United States with a high burden affecting morbidity, mortality and healthcare expenditure. The use of Fecal Microbiota Transplantation (FMT) is one of the current standard therapies for recurrent C. difficile infection (CDIr). One emerging promising approach is the use of monoclonal antibodies that bind to and neutralize C. difficile toxins such as Bezlotoxumab. We present the first case report on combining the third FMT with bezlotoxumab after the failure of standard-of-care antibiotics and two trials of FMT alone, with subsequent success in preventing the recurrence of refractory CDI for 12 weeks following treatment. This case highlight the need for further studies and guidelines to recommend the best combination among different treatment options and modalities.

RevDate: 2018-12-06

Allegretti JR, Fischer M, Sagi SV, et al (2018)

Fecal Microbiota Transplantation Capsules with Targeted Colonic Versus Gastric Delivery in Recurrent Clostridium difficile Infection: A Comparative Cohort Analysis of High and Lose Dose.

Digestive diseases and sciences pii:10.1007/s10620-018-5396-6 [Epub ahead of print].

BACKGROUND: Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridium. difficile infection (rCDI). FMT capsules have emerged, and it is unknown if delivery location and dose impact efficacy.

METHODS: We compared two cohorts of patients receiving two capsule formulations: gastric release (FMTgr) and targeted colonic release (FMTcr) at two different sites. Cohort A received FMTgr at (1) high dose: 60 capsules and low dose: 30 capsules. Patients in Cohort B received FMTcr at (1) high dose: 30 capsules (2) low dose: 10 capsules. Clinical cure rates and adverse events were monitored through week 8. Paired t-tests were used to compare diversity pre- and post-FMT.

RESULTS: 51 rCDI patients were enrolled. Cohort A contained n = 20 and Cohort B contained n = 31. Overall cure at week 8 for FMTgr was 75% (15/20) compared to 80.6% for FMTcr, (25/31), p = 0.63. Both formulations were safe with no serious adverse events. FMTcr was superior at increasing gut microbial diversity.

DISCUSSION: To our knowledge, this is the first study to compare targeted delivery of FMT capsules. While both capsules were safe and efficacious, microbial engraftment patterns were superior in FMTcr.

RevDate: 2018-12-06

Zhu Y, He C, Li X, et al (2018)

Gut microbiota dysbiosis worsens the severity of acute pancreatitis in patients and mice.

Journal of gastroenterology pii:10.1007/s00535-018-1529-0 [Epub ahead of print].

BACKGROUND: The gut is implicated in the pathogenesis of acute pancreatitis (AP) and the infectious complications of AP are commonly associated with enteric bacteria, yet whether gut microbiota dysbiosis participants in AP severity remains largely unknown.

METHODS: We collected clinical information and fecal samples from 165 adult participants, including 41 with mild AP (MAP), 59 with moderately severe AP (MSAP), 30 with severe AP (SAP) and 35 healthy controls (HC). The serum inflammatory cytokines and gut barrier indexes were detected. Male C57BL/6 mice with AP were established and injuries of pancreas were evaluated in antibiotic-treated mice, germ-free mice as well as those transplanted with fecal microbiota. The gut microbiota was analyzed by 16S rRNA gene sequencing.

RESULTS: The structure of gut microbiota was significantly different between AP and HC, and the disturbed microbiota was closely correlated with systematic inflammation and gut barrier dysfunction. Notably, the microbial composition changed further with the worsening of AP and the abundance of beneficial bacteria such as Blautia was decreased in SAP compared with MAP and MSAP. The increased capacity for the inferred pathway, bacterial invasion of epithelial cells in AP, highly correlated with the abundance of Escherichia-Shigella. Furthermore, the antibiotic-treated mice and germ-free mice exhibited alleviated pancreatic injury after AP induction and subsequent fecal microbiota transplantation in turn exacerbated the disease.

CONCLUSIONS: This study identifies the gut microbiota as an important mediator during AP and its dysbiosis is associated with AP severity, which suggests its role as potential therapeutic target.

RevDate: 2018-12-06

Bin P, Tang Z, Liu S, et al (2018)

Intestinal microbiota mediates Enterotoxigenic Escherichia coli-induced diarrhea in piglets.

BMC veterinary research, 14(1):385 pii:10.1186/s12917-018-1704-9.

BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) causes diarrhea in humans, cows, and pigs. The gut microbiota underlies pathology of several infectious diseases yet the role of the gut microbiota in the pathogenesis of ETEC-induced diarrhea is unknown.

RESULTS: By using an ETEC induced diarrheal model in piglet, we profiled the jejunal and fecal microbiota using metagenomics and 16S rRNA sequencing. A jejunal microbiota transplantation experiment was conducted to determine the role of the gut microbiota in ETEC-induced diarrhea. ETEC-induced diarrhea influenced the structure and function of gut microbiota. Diarrheal piglets had lower Bacteroidetes: Firmicutes ratio and microbiota diversity in the jejunum and feces, and lower percentage of Prevotella in the feces, but higher Lactococcus in the jejunum and higher Escherichia-Shigella in the feces. The transplantation of the jejunal microbiota from diarrheal piglets to uninfected piglets leaded to diarrhea after transplantation. Microbiota transplantation experiments also supported the notion that dysbiosis of gut microbiota is involved in the immune responses in ETEC-induced diarrhea.

CONCLUSION: We conclude that ETEC infection influences the gut microbiota and the dysbiosis of gut microbiota after ETEC infection mediates the immune responses in ETEC infection.

RevDate: 2018-12-06

Huang E, Kang S, Park H, et al (2018)

Differences in Anxiety Levels of Various Murine Models in Relation to the Gut Microbiota Composition.

Biomedicines, 6(4): pii:biomedicines6040113.

Psychobiotics are probiotic strains that confer mental health benefits to the host through the modulation of the gut microbial population. Mounting evidence shows that the gut microbiota play an important role in communication within the gut⁻brain axis. However, the relationship between the host genetics and the gut microbiota and their influence on anxiety are still not fully understood. Hence, in our research, we attempted to draw a connection between host genetics, microbiota composition, and anxiety by performing an elevated plus maze (EPM) test on four genetically different mice. Four different breeds of 5-week-old mice were used in this experiment: Balb/c, Orient C57BL/6N, Taconic C57BL/6N, and Taconic C57BL/6J. After 1 week of adaptation, their initial anxiety level was monitored using the EPM test via an EthoVision XT, a standardized software used for behavorial testing. Significant differences in the initial anxiety level and microbial composition were detected. Subsequently, the microbiota of each group was modulated by the administration of either a probiotic, fecal microbiota transplantation, or antibiotics. Changes were observed in host anxiety levels in correlation to the shift of the gut microbiota. Our results suggest that the microbiota, host genetics, and psychological symptoms are strongly related, yet the deeper mechanistic links need further exploration.

RevDate: 2018-12-03

Hu XF, Zhang WY, Wen Q, et al (2018)

Fecal Microbiota Transplantation Alleviates Myocardial Damage in Myocarditis by Restoring the Microbiota Composition.

Pharmacological research pii:S1043-6618(18)30355-4 [Epub ahead of print].

Myocarditis can be caused by several infectious and noninfectious causes. Treatment for myocarditis is still a difficult task in clinical practice. The gut microbiota is related to cardiovascular diseases such as atherosclerosis and hypertension. However, little is known about the role of the gut microbiota in myocarditis. In our study, we tested the hypothesis that gut dysbiosis is associated with myocarditis. We focused on whether fecal microbiota transplantation (FMT) can be used as an effective treatment for myocarditis. We used an experimental autoimmune myocarditis (EAM) mouse model. Fecal samples were isolated from the control and EAM groups for bacterial genome analysis. We observed an increase in microbial richness and diversity in the myocarditis mice. These changes were accompanied by an increased Firmicutes/Bacteroidetes ratio. We also evaluated the efficacy of FMT for the treatment of myocarditis. EAM mouse guts were repopulated with fecal contents from an untreated male mouse donor. We found that myocardial injury was improved by diminished inflammatory infiltration, showing that IFN-γ gene expression in the heart tissue and CD4+IFN-γ+ cells in the spleen were decreased after FMT in EAM mice. We also found that FMT was able to rebalance the gut microbiota by restoring the Bacteroidetes population and reshaping the microbiota composition. Myocarditis is associated with gut microbiota dysbiosis and characterized by an increased F/B ratio. FMT treatment can rebalance the gut microbiota and attenuate myocarditis. Thus, FMT may be a potential therapeutic strategy for the treatment of myocarditis.

RevDate: 2018-12-03

Leedahl DD, Personett HA, Nagpal A, et al (2018)

Prevention of Clostridium difficile Infection in Critically Ill Adults.

Pharmacotherapy [Epub ahead of print].

The incidence and severity of Clostridium difficile infection (CDI) remain high across intensive care units in the United States despite national efforts to decrease this escalating health care burden. Most published literature and guidelines address treatment rather than prevention, yet this approach may be too downstream to limit morbidity and mortality from the disease and its complications. Mechanisms to successfully prevent CDI include reducing modifiable risk factors and minimizing horizontal transmission of C. difficile spores between patients and the health care environment. Since CDI prevention is characterized by a bundled approach, it is difficult to quantify the individual impact of any one element; however, there are a number of patient- and facility-level strategies that can be considered for CDI prevention. Robust hygiene strategies, diagnostic and antimicrobial stewardship, and particular prophylaxis maneuvers such as continuation of oral vancomycin or fidaxomicin in the setting of systemic antibiotics have all demonstrated benefit. The preventive roles of deprescribing acid suppressants, routine use of probiotics, or early fecal microbiota transplantation remain unclear. The focus of this review is to summarize the evidence related to primary and secondary CDI prevention in critically ill adults and provide a concise implementation pathway for clinicians and policy makers. This article is protected by copyright. All rights reserved.

RevDate: 2018-12-03

Gong S, Yan Z, Liu Z, et al (2018)

Intestinal microbiota mediates the susceptibility to polymicrobial sepsis-induced liver injury by granisetron generation in mice.

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

Sepsis-induced liver injury is recognized as a key problem in intensive care units (ICUs). The gut microbiota has been touted as an important mediator of liver disease development; however, the precise roles of gut microbiota in regulating sepsis-induced liver injury are unknown. Here, we aimed to investigate the role of the gut microbiota in sepsis-induced liver injury and the underlying mechanism. Cecal ligation and puncture (CLP) was employed to induce polymicrobial sepsis and related liver injury. Fecal microbiota transplantation (FMT) was used to validate the roles of gut microbiota in these pathologies. Metabolomics analysis was performed to characterize the metabolic profile differences between sepsis-resistant (Res, survived to 7 days after CLP) and sepsis-sensitive (Sen, moribund before or approximately 24 h after CLP) mice. Mice gavaged with feces from Sen mice displayed more severe liver damage than did mice gavaged with feces from Res mice. The gut microbial metabolic profile between Sen and Res mice was different. In particular, the microbiota from Res mice generated more granisetron, a 5-hydroxytryptamine 3 (5-HT3) receptor antagonist, than the microbiota from Sen mice. Granisetron protected mice against CLP-induced death and liver injury. Moreover, proinflammatory cytokines expression by macrophages after LPS challenge was markedly reduced in the presence of granisetron. Both treatment with granisetron and genetic knockdown of the 5-HT3A receptor in cells suppressed NF-кB transactivation and p-p38 accumulation in macrophages. Gut microbial granisetron levels showed a significantly negative correlation with plasma ALT/AST levels in septic patients. Conclusion: Our study revealed that gut microbiota plays a key role in the sensitization of sepsis-induced liver injury and identified granisetron as a novel hepatoprotective compound during sepsis development. This article is protected by copyright. All rights reserved.

RevDate: 2018-12-03

Niederwerder MC (2018)

Fecal microbiota transplantation as a tool to treat and reduce susceptibility to disease in animals.

Veterinary immunology and immunopathology, 206:65-72.

Fecal microbiota transplantation (FMT) is the process by which fecal microbiota are donated from a healthy individual and subsequently transplanted into a diseased or young individual. The mechanism by which FMT is effective is believed to be due to enhanced beneficial microbes, increased microbiome diversity, and restored normal flora. Beneficial gut microorganisms not only play a role in maintaining an intestinal barrier and metabolizing nutrients, but importantly, these microbes help regulate local and systemic immune function. Although FMT has been described for several centuries, only recently has it been utilized as a mainstream therapy in humans and significantly considered for applications in other species. In humans and animals, gastrointestinal diseases are by far the most widely accepted FMT-treatable conditions; however, recent research has shown exceptional promise for FMT being used to treat or prevent other conditions, including those outside of the gastrointestinal tract. Overall, FMT is likely an underutilized, widely-available, and inexpensive tool for improving the health and response to disease in animals. In this review, the effects of FMT on veterinary diseases and potential applications for FMT in animals are discussed.

RevDate: 2018-12-03

Davido B, Batista R, Fessi H, et al (2018)

Fecal microbiota transplantation to eradicate vancomycin-resistant enterococci colonization in case of an outbreak.

Medecine et maladies infectieuses pii:S0399-077X(18)30002-7 [Epub ahead of print].

OBJECTIVE: A rapid and worrying emergence of vancomycin-resistant enterococci (VRE) gut colonization is occurring worldwide and may be responsible for outbreaks, especially in healthcare facilities. While no efficient decolonization strategies are recommended, we assessed fecal microbiota transplantation (FMT) to eradicate VRE colonization.

PATIENTS AND METHOD: Our main objective was to measure the impact of FMT on decolonization of VRE carriers, confirmed by at least two consecutive negative rectal swabs at one-week interval during a 3-month follow-up period. Patients received no antibiotic prior to the FMT.

RESULTS: After a month only three patients remained colonized with VRE. Decolonization was associated with 87.5% (n=7) of success after three months as only one patient remained colonized.

CONCLUSION: Our first results confirm that the FMT seems to be safe, with an impact on VRE colonization over time that may help control outbreaks.

RevDate: 2018-12-05

Carrera-Quintanar L, Ortuño-Sahagún D, Franco-Arroyo NN, et al (2018)

The Human Microbiota and Obesity: A Literature Systematic Review of In Vivo Models and Technical Approaches.

International journal of molecular sciences, 19(12): pii:ijms19123827.

Obesity is a noncommunicable disease that affects a considerable part of humanity. Recently, it has been recognized that gut microbiota constitutes a fundamental factor in the triggering and development of a large number of pathologies, among which obesity is one of the most related to the processes of dysbiosis. In this review, different animal model approaches, methodologies, and genome scale metabolic databases were revisited to study the gut microbiota and its relationship with metabolic disease. As a data source, PubMed for English-language published material from 1 January 2013, to 22 August 2018, were screened. Some previous studies were included if they were considered classics or highly relevant. Studies that included innovative technical approaches or different in vivo or in vitro models for the study of the relationship between gut microbiota and obesity were selected after a 16-different-keyword exhaustive search. A clear panorama of the current available options for the study of microbiota's influence on obesity, both for animal model election and technical approaches, is presented to the researcher. All the knowledge generated from the study of the microbiota opens the possibility of considering fecal transplantation as a relevant therapeutic alternative for obesity and other metabolic disease treatment.

RevDate: 2018-11-30

Mathias F, Curti C, Montana M, et al (2018)

Management of adult Clostridium difficile digestive contaminations: a literature review.

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology pii:10.1007/s10096-018-3419-z [Epub ahead of print].

Clostridium difficile infections (CDI) dramatically increased during the last decade and cause a major public health problem. Current treatments are limited by the high disease recurrence rate, severity of clinical forms, disruption of the gut microbiota, and colonization by vancomycin-resistant enterococci (VRE). In this review, we resumed current treatment options from official recommendation to promising alternatives available in the management of adult CDI, with regard to severity and recurring or non-recurring character of the infection. Vancomycin remains the first-line antibiotic in the management of mild to severe CDI. The use of metronidazole is discussed following the latest US recommendations that replaced it by fidaxomicin as first-line treatment of an initial episode of non-severe CDI. Fidaxomicin, the most recent antibiotic approved for CDI in adults, has several advantages compared to vancomycin and metronidazole, but its efficacy seems limited in cases of multiple recurrences. Innovative therapies such as fecal microbiota transplantation (FMT) and antitoxin antibodies were developed to limit the occurrence of recurrence of CDI. Research is therefore very active, and new antibiotics are being studied as surotomycin, cadazolid, and rinidazole.

RevDate: 2018-11-29

Takahashi M, Ishikawa D, Sasaki T, et al (2018)

Fecal Freezing Preservation Period Influences Colonization Ability for Fecal Microbiota Transplantation.

Journal of applied microbiology [Epub ahead of print].

AIMS: There has been growing interest in fecal microbiota transplantation (FMT) as treatment. Although, frozen donor feces preserved at -20°C has been widely used for practical advantages, freezing at -20°C can affect bacterial viability. Adequacy evaluation of fresh and frozen feces as the transplant is necessary for the methodological improvement of FMT.

METHODS AND RESULTS: The viable bacterial compositions of fecal specimens under fresh and freezing conditions were compared by a microbiome analysis using propidium monoazide (PMA microbiome). In addition, recovery abilities from bacterial reduction by antibiotics were compared between fresh and frozen FMT using a murine model. PMA microbiome results suggested that freezing and freeze-thawing didn't significantly affect in vitro fecal bacterial viability. However, the recovery effect from antimicrobial cleansing in frozen FMT was reduced in a freezing time-dependent manner, especially prominent in Actinobacteria and Bacteroidetes phyla.

CONCLUSIONS: Short-term freezing preservation of feces exhibited maintenance of enteric colonization ability in frozen FMT in comparison to 1 month -20°C-preservation.

SIGNIFICANCE AND IMPACT: Long-term -20°C-preservation of transplanted feces can result in instability of the clinical outcome in FMT therapy. The standardization of practical procedures of FMT therapy according to disease types is desirable. This article is protected by copyright. All rights reserved.

RevDate: 2018-11-28

Shi YC, YS Yang (2018)

Fecal microbiota transplantation: Current status and challenges in China.

JGH open : an open access journal of gastroenterology and hepatology, 2(4):114-116 pii:JGH312071.

RevDate: 2018-11-27

Imdad A, Nicholson MR, Tanner-Smith EE, et al (2018)

Fecal transplantation for treatment of inflammatory bowel disease.

The Cochrane database of systematic reviews, 11:CD012774 [Epub ahead of print].

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic, relapsing disease of the gastrointestinal tract that is thought to be associated with a complex interplay between microbes and the immune system, leading to an abnormal inflammatory response in genetically susceptible individuals. Dysbiosis, characterized by the alteration of the composition of the resident commensal bacteria in a host compared to healthy individuals, is thought to play a major role in the pathogenesis of ulcerative colitis (UC) and Crohn's disease (CD), two subtypes of IBD. There is growing interest to correct the underlying dysbiosis through the use of fecal microbiota transplantation (FMT) for the treatment of IBD.

OBJECTIVES: The objective of this systematic review was to assess the efficacy and safety of FMT for the treatment of IBD.

SEARCH METHODS: We searched the MEDLINE, Embase, Cochrane Library, and Cochrane IBD Group Specialized Register databases from inception to 19 March 2018. We also searched ClinicalTrials.gov, ISRCTN metaRegister of Controlled Trials, and the Conference Proceedings Citation Index.

SELECTION CRITERIA: Only randomized trials or non-randomized studies with a control arm were considered for inclusion. Adults or pediatric participants with UC or CD were eligible for inclusion. Eligible interventions were FMT defined as the administration of fecal material containing distal gut microbiota from a healthy donor to the gastrointestinal tract of a someone with UC or CD. The comparison group included participants who did not receive FMT and were given placebo, autologous FMT, or no intervention.

DATA COLLECTION AND ANALYSIS: Two authors independently screened the titles and extracted data from the included studies. We used the Cochrane risk of bias tool to assess study bias. The primary outcomes were induction of clinical remission, clinical relapse, and serious adverse events. Secondary outcomes included clinical response, endoscopic remission and endoscopic response, quality of life scores, laboratory measures of inflammation, withdrawals, and microbiome outcomes. We calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI) for dichotomous outcomes and the mean difference and 95% CI for continuous outcomes. Random-effects meta-analysis models were used to synthesize effect sizes across trials. The overall certainty of the evidence supporting the primary and selected secondary outcomes was rated using the GRADE criteria.

MAIN RESULTS: Four studies with a total of 277 participants were included. These studies assessed the efficacy of FMT for treatment of UC in adults; no eligible trials were found for the treatment of CD. Most participants had mild to moderate UC. Two studies were conducted in Australia, one study was conducted in Canada, and another in the Netherlands. Three of the included studies administered FMT via the rectal route and one study administered FMT via the nasoduodenal route. Three studies were rated as low risk of bias. One study (abstract publication) was rated as unclear risk of bias. Combined results from four studies (277 participants) suggest that FMT increases rates of clinical remission by two-fold in patients with UC compared to controls. At 8 weeks, 37% (52/140) of FMT participants achieved remission compared to 18% (24/137) of control participants (RR 2.03, 95 % CI, 1.07 to 3.86; I² = 50%; low certainty evidence). One study reported data on relapse at 12 weeks among participants who achieved remission. None of the FMT participants (0/7) relapsed at 12 weeks compared to 20% of control participants (RR 0.28, 95% CI 0.02 to 4.98, 17 participants, very low certainty evidence). It is unclear whether there is a difference in serious adverse event rates between the intervention and control groups. Seven per cent (10/140) of FMT participants had a serious adverse event compared to 5% (7/137) of control participants (RR 1.40, 95% CI 0.55 to 3.58; 4 studies; I² = 0%; low certainty evidence). Serious adverse events included worsening of UC necessitating intravenous steroids or surgery; infection such as Clostridium difficile and cytomegalovirus, small bowel perforation and pneumonia. Adverse events were reported by two studies and the pooled data did not show any difference between the study groups. Seventy-eight per cent (50/64) of FMT participants had an adverse event compared to 75% (49/65) of control participants (RR 1.03, 95% CI 0.81 to 1.31; I² = 31%; moderate certainty evidence). Common adverse events included abdominal pain, nausea, flatulence, bloating, upper respiratory tract infection, headaches, dizziness, and fever. Four studies reported on clinical response at 8 weeks. Forty-nine per cent (68/140) of FMT participants had a clinical response compared to 28% (38/137) of control participants (RR 1.70, 95% CI 0.98 to 2.95, I² = 50%, low certainty evidence). Endoscopic remission at 8 weeks was reported by three studies and the combined results favored FMT over the control group. Thirty per cent (35/117) of FMT participants achieved endoscopic remission compared to 10% (11/112) of control participants (RR 2.96, 95 % CI 1.60 to 5.48, I² = 0%; low certainty evidence).

AUTHORS' CONCLUSIONS: Fecal microbiota transplantation may increase the proportion of participants achieving clinical remission in UC. However, the number of identified studies was small and the quality of evidence was low. There is uncertainty about the rate of serious adverse events. As a result, no solid conclusions can be drawn at this time. Additional high-quality studies are needed to further define the optimal parameters of FMT in terms of route, frequency, volume, preparation, type of donor and the type and disease severity. No studies assessed efficacy of FMT for induction of remission in CD or in pediatric participants. In addition, no studies assessed long-term maintenance of remission in UC or CD. Future studies are needed to address the therapeutic benefit of FMT in CD and the long-term FMT-mediated maintenance of remission in UC or CD.

RevDate: 2018-11-27

Wang Y, Wiesnoski DH, Helmink BA, et al (2018)

Author Correction: Fecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis.

In the version of this article originally published, an author was missing from the author list. Alexander J. Lazar should have been included between Jorge M. Blando and James P. Allison. The author has been added to the list, and the author contributions section has been updated to include Alexander J. Lazar's contribution to the study. The error has been corrected in the print, PDF and HTML versions of the manuscript.

RevDate: 2018-11-26

Mehta R, Kabrawala M, Nandwani S, et al (2018)

Preliminary experience with single fecal microbiota transplant for treatment of recurrent overt hepatic encephalopathy-A case series.

Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology pii:10.1007/s12664-018-0906-1 [Epub ahead of print].

Experimental studies demonstrated that fecal microbiota transplant (FMT) may reverse intestinal microbial dysbiosis. In this retrospective case series, we share our experience of treating recurrent overt hepatic encephalopathy (HE) with single FMT treatment. A total of 10 patients, age ranged from 25 to 65 years, were treated with single FMT through colonoscopy using fecal material received from rigorously screened patient-identified donors. There was sustained clinical response with single FMT treatment in 6 patients at post-treatment week 20. Arterial ammonia concentration decreased considerably (96 [87.25-117.75] vs. 74 [70-82]; p = 0.024) at post-treatment week 20. Moreover, there was statistically significant decrease in Child-Turcotte-Pugh (CTP) score (9.5 [9-10.75] vs. 8 [7-8]; p = 0.005) and model for end-stage liver disease (MELD) score (18 [16.25-19] vs. 15 [14-16]; p = 0.008). Four patients experienced six adverse-events. Overt HE and re-hospitalization were observed in 3 and 2 patients, respectively. One patient (who also experienced overt HE) died within 2 months of the index procedure.

RevDate: 2018-11-26

Dai Z, Zhang J, Wu Q, et al (2018)

The role of microbiota in the development of colorectal cancer.

International journal of cancer [Epub ahead of print].

Colorectal cancer is the third largest cancer in worldwide and has been proven to be closely related to the intestinal microbiota. Many reports and clinical studies have shown that intestinal microbial behavior may lead to pathological changes in the host intestines. The changes can be divided into epigenetic changes and carcinogenic changes at the gene level, which ultimately promote the production and development of colorectal cancer. This article reviews the pathways of microbial signaling in the intestinal epithelial barrier, the role of microbiota in inflammatory colorectal tumors, and typical microbial carcinogenesis. Finally, by gaining a deeper understanding of the intestinal microbiota, we hope to achieve the goal of treating colorectal cancer using current microbiota technologies, such as fecal microbiological transplantation.

RevDate: 2018-11-25

Saïdani N, Lagier JC, Cassir N, et al (2018)

Fecal microbiota transplantation shortens the colonization period and allows the re-entry of patients carrying carbapenamase-producing bacteria into medical care facilities.

International journal of antimicrobial agents pii:S0924-8579(18)30339-X [Epub ahead of print].

BACKGROUND: Colonization with carbapenemase producing Enterobacteriaceae or Acinetobacter (CPE/A) is associated with complex medical care requiring implementation of specific isolation policies and limitation of patient discharge to other medical facilities. Fecal Microbiota Transplantation (FMT) has been proposed in order to reduce the duration of gut colonization.

OBJECTIVES: We investigated whether a dedicated protocol of FMT could reduce the negativation time of CPE/A intestinal carriage in patients whose medical care has been delayed due to such colonization.

METHOD: We performed a matched case-control retrospective study between patients who received FMT treatment and those who did not among CPE/A colonized patient addressed for initial clustering at our institute. We adjusted two controls per case based on sex, age, bacterial species and carbapenemase type. The primary outcome was the delay in negativation of rectal-swab cultures.

RESULTS: At day 14 post-FMT, 8/10 (80%) treated patients were cleared for intestinal CPE/A carriage. In the control group, 2/20 (10%) had a spontaneous clearance at day 14 after CPE/A diagnostic. FMT led patients to reduce the delay of decolonization (median 3 days post-FMT for treated patients versus 50.5 days after the first documentation of digestive carriage for control patients) and discharge from the hospital (median 19.5 days post-FMT for treated patients versus 41 for control patients).

CONCLUSION: FMT is a safe and time saving procedure to discharge CPE/A-colonized patients from the hospital. A standardized protocol including 5 days of antibiotic treatment, bowel cleansing and systematic indwelling devices removal should improve the effectiveness of the protocol.

RevDate: 2018-11-24

Tillmann S, Abildgaard A, Winther G, et al (2018)

Altered fecal microbiota composition in the Flinders sensitive line rat model of depression.

Psychopharmacology pii:10.1007/s00213-018-5094-2 [Epub ahead of print].

RATIONALE: The gut microbiota is increasingly recognized as a potential mediator of psychiatric diseases. Depressed patients have been shown to have a different microbiota composition compared with healthy controls, and several lines of research now aim to restore this dysbiosis. To develop novel treatments, preclinical models may provide novel mechanistic insights.

OBJECTIVE AND METHODS: We characterized the gut microbiota of male adult Flinders sensitive line (FSL) rats, an animal model of depression, and their controls, Flinders resistant line (FRL) rats using 16S rRNA amplicon sequencing. Moreover, we performed fecal microbiota transplantation (using saline or pooled FRL/FSL feces) to study if the potential strain-specific differences could be transferred from one strain to the other, and if these differences were reflected in their depressive-like behavior in the forced swim test.

RESULTS: FSL rats tended to have lower bacterial richness and altered relative abundances of several bacterial phyla, families, and species, including higher Proteobacteria and lower Elusimicrobia and Saccharibacteria. There was a clear separation between FRL and FSL rat strains, but no effect of treatment, i.e., the bacterial composition of FSL rats receiving FRL feces was still more similar to FSL and not FRL rats. Similarly, the transplantation did not reverse behavioral differences in the forced swim test, although FSL feces significantly increased immobility compared with saline.

CONCLUSIONS: Our study showed that the gut microbiota composition of the depressive-like rats markedly differed from their controls, which may be of value for future microbiota-targeted work in this and similar animal models.

RevDate: 2018-11-22

Bulow C, Langdon A, Hink T, et al (2018)

Impact of Amoxicillin-Clavulanate followed by Autologous Fecal Microbiota Transplantation on Fecal Microbiome Structure and Metabolic Potential.

mSphere, 3(6): pii:3/6/e00588-18.

Strategies to prevent multidrug-resistant organism (MDRO) infections are scarce, but autologous fecal microbiota transplantation (autoFMT) may limit gastrointestinal MDRO expansion. AutoFMT involves banking one's feces during a healthy state for later use in restoring gut microbiota following perturbation. This pilot study evaluated the effect of autoFMT on gastrointestinal microbiome taxonomic composition, resistance gene content, and metabolic capacity after exposure to amoxicillin-clavulanic acid (Amox-Clav). Ten healthy participants were enrolled. All received 5 days of Amox-Clav. Half were randomized to autoFMT, derived from stool collected pre-antimicrobial exposure, by enema, and half to saline enema. Participants submitted stool samples pre- and post-Amox-Clav and enema and during a 90-day follow-up period. Shotgun metagenomic sequencing revealed taxonomic composition, resistance gene content, and metabolic capacity. Amox-Clav significantly altered gut taxonomic composition in all participants (n = 10, P < 0.01); however, only three participants exhibited major changes at the phylum level following exposure. In the cohort as a whole, beta-lactamase genes were enriched following Amox-Clav (P < 0.05), and predicted metabolic capacity was significantly altered (P < 0.01). Species composition, metabolic capacity, and beta-lactamase abundance returned to pre-antimicrobial exposure state 7 days after either autoFMT or saline enema (P > 0.05, compared to enrollment). Alterations to microbial metabolic capacity occurred following antimicrobial exposure even in participants without substantial taxonomic disruption, potentially creating open niches for pathogen colonization. Our findings suggest that metabolic potential is an important consideration for complete assessment of antimicrobial impact on the microbiome. AutoFMT was well tolerated and may have contributed to phylogenetic recovery. (This study has been registered at ClinicalTrials.gov under identifier NCT02046525.)IMPORTANCE The spread of multidrug resistance among pathogenic organisms threatens the efficacy of antimicrobial treatment options. The human gut serves as a reservoir for many drug-resistant organisms and their resistance genes, and perturbation of the gut microbiome by antimicrobial exposure can open metabolic niches to resistant pathogens. Once established in the gut, antimicrobial-resistant bacteria can persist even after antimicrobial exposure ceases. Strategies to prevent multidrug-resistant organism (MDRO) infections are scarce, but autologous fecal microbiota transplantation (autoFMT) may limit gastrointestinal MDRO expansion. AutoFMT involves banking one's feces during a healthy state for later use in restoring gut microbiota following perturbation. This pilot study evaluated the effect of amoxicillin-clavulanic acid (Amox-Clav) exposure and autoFMT on gastrointestinal microbiome taxonomic composition, resistance gene content, and metabolic capacity. Importantly, we found that metabolic capacity was perturbed even in cases where gross phylogeny remained unchanged and that autoFMT was safe and well tolerated.

RevDate: 2018-11-21

Riddle MS, BA Connor (2018)

Fecal microbiota transplantation: what is the role in travelers' diarrhea?.

Journal of travel medicine pii:5194706 [Epub ahead of print].

RevDate: 2018-11-20

Chen D, Wu J, Jin D, et al (2018)

Fecal microbiota transplantation in cancer management: Current status and perspectives.

International journal of cancer [Epub ahead of print].

The human gut is home to a large and diverse microbial community, comprising about 1000 bacterial species. The gut microbiota exists in a symbiotic relationship with its host, playing a decisive role in the host's nutrition, immunity, and metabolism. Accumulating studies have revealed the associations between gut dysbiosis or some special bacteria and various cancers. Emerging data suggest that gut microbiota can modulate the effectiveness of cancer therapies, especially immunotherapy. Manipulating the microbial populations with therapeutic intent has become a hot topic of cancer research, and the most dramatic manipulation of gut microbiota refers to fecal microbiota transplantation (FMT) from healthy individuals to patients. FMT has demonstrated remarkable clinical efficacy against Clostridium difficile infection (CDI) and it is highly recommended for the treatment of recurrent or refractory CDI. Lately, interest is growing in the therapeutic potential of FMT for other diseases, including cancers. We briefly reviewed the current researches about gut microbiota and its link to cancer, and then summarized the recent pre-clinical and clinical evidence to indicate the potential of FMT in cancer management as well as cancer-treatment associated complications. We also presented the rationale of FMT for cancer management such as reconstruction of intestinal microbiota, amelioration of bile acid metabolism, and modulation of immunotherapy efficacy. This article would help to better understand this new therapeutic approach for cancer patients by targeting gut microbiota. This article is protected by copyright. All rights reserved.

RevDate: 2018-11-22

Ohara T, T Suzutani (2018)

Efficacy of fecal microbiota transplantation in a patient with chronic intractable constipation.

Clinical case reports, 6(11):2029-2032 pii:CCR31798.

We have presented the first case report of FMT therapy for a patient with chronic intractable constipation. This therapy resulted in good, medium-term outcomes. Follow-up analysis of the intestinal flora suggested that transplanted microbes from the donor, particularly Bifidobacterium and Clostridium cluster IX, may have been incorporated into the recipient.

RevDate: 2018-11-20

Weis M (2018)

Impact of the gut microbiome in cardiovascular and autoimmune diseases.

Clinical science (London, England : 1979), 132(22):2387-2389 pii:CS20180410.

The gut microbiome functions like an endocrine organ, generating enzymes and bioactive metabolites, which affect host physiology. In addition metabolism-independent processes like impaired intestinal barrier function may result in bacterial translocation and an increased inflammation. Specific microbe-associated molecular patterns (MAMPs) have been detected that induce immune activation via cognate pattern-recognition receptors on host immune cells, with subsequent consequences on inflammatory-induced endothelial dysfunction. Alterations in intestinal microbial and metabolic composition play an important role in human health and disease, including cardiovascular and autoimmune diseases. Changes in the composition of gut microbiota (dysbiosis) are linked to chronic inflammation, thrombosis, atherogenesis, chronic heart, and kidney disease, as well as to autoimmune diseases like systemic lupus erythematodes. Although non-selective approaches that broadly alter microbial community structure, such as prebiotics, probiotics, and fecal microbial transplantation, may have some promise, targeting defined microbial pathways and adjacent host immune responses may be the ultimate scientific goal.

RevDate: 2018-11-21

Li X, Gao X, Hu H, et al (2018)

Clinical Efficacy and Microbiome Changes Following Fecal Microbiota Transplantation in Children With Recurrent Clostridium Difficile Infection.

Frontiers in microbiology, 9:2622.

Fecal microbiota transplantation (FMT) has been shown as an effective treatment for recurrent clostridium difficile infection (RCDI) in adults. In this study, we aim to evaluate the clinical efficacy of FMT in treating children with RCDI, and explore fecal microbiota changes during FMT treatment. A total of 11 RCDI subjects with a median age of 3.5 years were enrolled in this single-center prospective pilot study. All patients were cured (11/11, 100%) by FMT either through upper gastrointestinal tract route with a nasointestinal tube (13/16, 81.2%) or lower gastrointestinal tract route with a rectal tube (3/16, 18.8%). The cure rate of single FMT was 63.6% (7/11), and 4 (4/11, 36.4%) cases were performed with 2 or 3 times of FMT. Mild adverse events were reported in 4 children (4/11, 36.4%), including transient diarrhea, mild abdominal pain, transient fever and vomit. Gut microbiota composition analysis of 59 fecal samples collected from 34 participants (9 RCDI children, 9 donors and 16 health controls) showed that the alpha diversity was lower in pediatric RCDI patients before FMT than the healthy controls and donors, and fecal microbial community of pre-FMT samples (beta diversity) was apart from that of healthy controls and donors. No significant differences in alpha diversity, beta diversity or phylogenetic distance were detected between donors and healthy controls. Both the richness and diversity of gut microbiota were improved in the pediatric RCDI patients after FMT, and the bacteria community was shifted closer to the donor and healthy control group. Furthermore, FMT re-directed gut microbiome functions of pediatric RCDI toward a health state. Our results indicate that it is safe and tolerant to use FMT in treating pediatric RCDI. FMT shifted the gut microbiome composition and function in children with RCDI toward a healthy state.

RevDate: 2018-11-19

Sood A, Mahajan R, Juyal G, et al (2018)

Efficacy of fecal microbiota therapy in steroid dependent ulcerative colitis: a real world intention-to-treat analysis.

Intestinal research pii:ir.2018.00089 [Epub ahead of print].

Background/Aims: Four high-quality randomized controlled trials have proven the efficacy of fecal microbiota transplantation (FMT) in active ulcerative colitis (UC). We assessed the efficacy of FMT in a real-world setting involving steroid-dependent patients with UC.

Methods: This was a single-center prospective analysis of data from steroid-dependent patients with UC treated with FMT from September 2015 to September 2017 at the Dayanand Medical College, a tertiary care center in India. Fecal samples from random unrelated donors were administered through colonoscopy at weeks 0, 2, 6, 10, 14, 18, and 22. The primary outcome was achievement of steroid-free clinical remission, and the secondary outcomes were clinical response and endoscopic remission at 24 weeks. Modified intention-to-treat analysis was performed, which included subjects who underwent at least 1 FMT.

Results: Of 345 patients with UC treated during the study period, 49 (14.2%) had steroid-dependent UC. Of these 49 patients, 41 underwent FMT: 33 completed 7 sessions over 22 weeks according to the protocol, and 8 discontinued treatment (non-response, 5; lost to follow-up, 2; and fear of adverse effects, 1). At week 24, steroid-free clinical remission was achieved in 19 out of 41 (46.3%) patients, whereas clinical response and endoscopic remission were achieved in 31 out of 41 (75.6%) and 26 out of 41 (63.4%) patients, respectively. All patients with clinical response were able to withdraw steroids. There were no serious adverse events necessitating discontinuation.

Conclusions: A multisession FMT via the colonoscopic route is a promising therapeutic option for patients with steroid-dependent UC, as it can induce clinical remission and aid in steroid withdrawal.

RevDate: 2018-11-29

Kaito S, Toya T, Yoshifuji K, et al (2018)

Fecal microbiota transplantation with frozen capsules for a patient with refractory acute gut graft-versus-host disease.

Blood advances, 2(22):3097-3101.

RevDate: 2018-11-22

Zhou W, Chow KH, Fleming E, et al (2018)

Selective colonization ability of human fecal microbes in different mouse gut environments.

The ISME journal pii:10.1038/s41396-018-0312-9 [Epub ahead of print].

Mammalian hosts constantly interact with diverse exogenous microbes, but only a subset of the microbes manage to colonize due to selective colonization resistance exerted by host genetic factors as well as the native microbiota of the host. An important question in microbial ecology and medical science is if such colonization resistance can discriminate closely related microbial species, or even closely related strains of the same species. Using human-mouse fecal microbiota transplantation and metagenomic shotgun sequencing, we reconstructed colonization patterns of human fecal microbes in mice with different genotypes (C57BL6/J vs. NSG) and with or without an intact gut microbiota. We found that mouse genotypes and the native mouse gut microbiota both exerted different selective pressures on exogenous colonizers: human fecal Bacteroides successfully established in the mice gut, however, different species of Bacteroides selectively enriched under different gut conditions, potentially due to a multitude of functional differences, ranging from versatility in nutrient acquisition to stress responses. Additionally, different clades of Bacteroides cellulosilyticus strains were selectively enriched in different gut conditions, suggesting that the fitness of conspecific microbial strains in a novel host environment could differ.

RevDate: 2018-11-14

Mazzawi T, Lied GA, Sangnes DA, et al (2018)

The kinetics of gut microbial community composition in patients with irritable bowel syndrome following fecal microbiota transplantation.

PloS one, 13(11):e0194904 pii:PONE-D-17-36974.

BACKGROUND: Gut microbiota alterations are important in irritable bowel syndrome (IBS). The aim was to investigate the effect of fecal microbiota transplantation (FMT) on gut microbiota and the symptoms in patients with IBS.

MATERIAL AND METHODS: The study included 13 IBS patients according to Rome III criteria and 13 healthy donors. Freshly donated feces were administered to the descending part of the duodenum via a gastroscope. Feces were collected from donors and patients before FMT, and from the patients at 1, 3 and 12 weeks and donors and patients at 20/28 weeks after FMT. Microbiota analysis was performed using GA-map Dysbiosis test (Genetic Analysis AS, Oslo, Norway). The patients completed the following questionnaires before and at the aforementioned weeks after FMT: IBS Symptom Questionnaire (IBS-SQ), IBS-Symptom Severity Scoring system (IBS-SSS), Short Form of Nepean Dyspepsia Index (SF-NDI), Bristol stool form scale, the Eysenck Personality Questionnaire-Neuroticism and Hospital Anxiety and Depression.

RESULTS: Donors and IBS patients had significantly different bacterial strain signals before FMT (Ruminococcus gnavus, Actinobacteria and Bifidobacteria) that became non-significant after 3 weeks following FMT. The changes in gut microbiota were similar between donors and patients at 20/28 weeks after FMT. Thus, patients' microbiota profiles became more-or-less similar to donors. The scores of all the questionnaires were significantly improved at all time points following FMT. No reported adverse effects.

CONCLUSIONS: FMT was associated with a change in gut microbiota and improvement in IBS symptoms and quality of life lasting for up to 28 weeks.

TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03333291.

RevDate: 2018-11-25

Kaliannan K, Robertson RC, Murphy K, et al (2018)

Estrogen-mediated gut microbiome alterations influence sexual dimorphism in metabolic syndrome in mice.

Microbiome, 6(1):205 pii:10.1186/s40168-018-0587-0.

BACKGROUND: Understanding the mechanism of the sexual dimorphism in susceptibility to obesity and metabolic syndrome (MS) is important for the development of effective interventions for MS.

RESULTS: Here we show that gut microbiome mediates the preventive effect of estrogen (17β-estradiol) on metabolic endotoxemia (ME) and low-grade chronic inflammation (LGCI), the underlying causes of MS and chronic diseases. The characteristic profiles of gut microbiome observed in female and 17β-estradiol-treated male and ovariectomized mice, such as decreased Proteobacteria and lipopolysaccharide biosynthesis, were associated with a lower susceptibility to ME, LGCI, and MS in these animals. Interestingly, fecal microbiota-transplant from male mice transferred the MS phenotype to female mice, while antibiotic treatment eliminated the sexual dimorphism in MS, suggesting a causative role of the gut microbiome in this condition. Moreover, estrogenic compounds such as isoflavones exerted microbiome-modulating effects similar to those of 17β-estradiol and reversed symptoms of MS in the male mice. Finally, both expression and activity of intestinal alkaline phosphatase (IAP), a gut microbiota-modifying non-classical anti-microbial peptide, were upregulated by 17β-estradiol and isoflavones, whereas inhibition of IAP induced ME and LGCI in female mice, indicating a critical role of IAP in mediating the effects of estrogen on these parameters.

CONCLUSIONS: In summary, we have identified a previously uncharacterized microbiome-based mechanism that sheds light upon sexual dimorphism in the incidence of MS and that suggests novel therapeutic targets and strategies for the management of obesity and MS in males and postmenopausal women.

RevDate: 2018-11-28

Wang Y, Wiesnoski DH, Helmink BA, et al (2018)

Fecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis.

Nature medicine pii:10.1038/s41591-018-0238-9 [Epub ahead of print].

We report the first case series of immune checkpoint inhibitors (ICI)-associated colitis successfully treated with fecal microbiota transplantation, with reconstitution of the gut microbiome and a relative increase in the proportion of regulatory T-cells within the colonic mucosa. These preliminary data provide evidence that modulation of the gut microbiome may abrogate ICI-associated colitis.

RevDate: 2018-11-11

Fang X (2018)

Microbial treatment: the potential application for Parkinson's disease.

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology pii:10.1007/s10072-018-3641-6 [Epub ahead of print].

Alterations in the composition of the intestinal flora are associated with the pathophysiology of Parkinson's disease (PD). More importantly, the possible cause-effect links between gut flora and PD pathogenesis have been identified using PD animal models. Recent studies have found that probiotics improve the symptoms associated with constipation in PD patients. In addition, fecal microbiota transplantation (FMT) was recently shown to provide a protective effect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in mice. Effective microbial therapy for PD includes probiotics and FMT. Therefore, microbial therapy may be a useful and novel approach for treatment of PD. In this review, I discuss the use of microbial treatment in PD.

RevDate: 2018-11-11

Prado C, Michels M, Ávila P, et al (2018)

The protective effects of fecal microbiota transplantation in an experimental model of necrotizing enterocolitis.

Journal of pediatric surgery pii:S0022-3468(18)30668-7 [Epub ahead of print].

BACKGROUND: Necrotizing enterocolitis (NEC) is a serious disease that affects premature neonates, causing high mortality. In the search for new options of treatment it was investigated whether fecal microbiota transplantation (FMT) decreased the inflammatory response during NEC development in experimental model.

METHODS: Wistar rats were used and divided as follows: naïve, control (NEC induction), FMT-before (transplantation of microbiota before insult) and FMT-after (microbiota transplantation after insult). The microbiota transplantation was performed by administering a feces solution obtained from an adult donor rat. The induction of enterocolitis involves feeding by artificial formula, hypothermia, hypoxia and endotoxin administration. MPO activity, TNF-α, IL-1β and IL-6 levels, oxidative and nitrosative damage and the grade of intestinal mucosa lesion were analyzed.

RESULTS: The control group had a significant increase of inflammatory and oxidative parameters when compared to naive animals. Both FMT-before and after decreased all inflammatory and oxidative damage parameters when compared to control group. This was also true to the intestinal mucosa damage.

CONCLUSION: FMT administered just before or after NEC induction improved gut and systemic inflammation, and gut oxidative damage and intestinal injury.

RevDate: 2018-11-20

Ma C, Sun Z, Zeng B, et al (2018)

Cow-to-mouse fecal transplantations suggest intestinal microbiome as one cause of mastitis.

Microbiome, 6(1):200 pii:10.1186/s40168-018-0578-1.

BACKGROUND: Mastitis, which affects nearly all lactating mammals including human, is generally thought to be caused by local infection of the mammary glands. For treatment, antibiotics are commonly prescribed, which however are of concern in both treatment efficacy and neonate safety. Here, using bovine mastitis which is the most costly disease in the dairy industry as a model, we showed that intestinal microbiota alone can lead to mastitis.

RESULTS: Fecal microbiota transplantation (FMT) from mastitis, but not healthy cows, to germ-free (GF) mice resulted in mastitis symptoms in mammary gland and inflammations in serum, spleen, and colon. Probiotic intake in parallel with FMT from diseased cows led to relieved mastitis symptoms in mice, by shifting the murine intestinal microbiota to a state that is functionally distinct from either healthy or diseased microbiota yet structurally similar to the latter. Despite conservation in mastitis symptoms, diseased cows and mice shared few mastitis-associated bacterial organismal or functional markers, suggesting striking divergence in mastitis-associated intestinal microbiota among lactating mammals. Moreover, an "amplification effect" of disease-health distinction in both microbiota structure and function was apparent during the cow-to-mouse FMT.

CONCLUSIONS: Hence, dysbiosis of intestinal microbiota may be one cause of mastitis, and probiotics that restore intestinal microbiota function are an effective and safe strategy to treat mastitis.

RevDate: 2018-11-08

DeFilipp Z, Hohmann E, Jenq RR, et al (2018)

Fecal microbiota transplantation: restoring the injured microbiome after allogeneic hematopoietic cell transplantation.

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation pii:S1083-8791(18)30693-1 [Epub ahead of print].

Disruption of the intestinal microbiome early after allogeneic hematopoietic cell transplantation (allo-HCT) has been linked to adverse outcomes in transplant recipients. To date, it remains unknown as to whether microbiome-directed interventions will be able to impact important clinical endpoints. Fecal microbiota transplantation (FMT) is a compelling intervention to restore healthy diversity to the intestinal microenvironment after allo-HCT, but currently has no established role in transplant recipients. In this review, we examine the utilization of FMT as treatment for Clostridium difficile infections and acute graft-versus-host disease, as well as a restorative intervention early after allo-HCT. Ongoing and planned studies will help determine the ultimate role of FMT in recipients of allo-HCT.

RevDate: 2018-11-14

Niccum BA, Stein DJ, Behm BW, et al (2018)

Zinc Deficiency and the Recurrence of Clostridium difficile Infection after Fecal Microbiota Transplant: A Retrospective Cohort Study.

Journal of nutrition and metabolism, 2018:9682975.

Background: Fecal microbiota transplant (FMT) is an effective therapy for recurrent Clostridium difficile infection (CDI). However, in 12% of patients treated with FMT, CDI recurs within one month. Zinc deficiency predicts increased diarrheal frequency in malnourished children, but little is known about its association with FMT outcome. We hypothesized that zinc levels were an independent predictor of CDI recurrence after FMT.

Methods: We performed a retrospective cohort study of 80 patients (mean age, 66; 59 women) receiving FMT for CDI from 9/2013-9/2016 at a tertiary care center. Zinc levels were measured within 90 days before FMT. The primary outcome was CDI recurrence within 90 days after FMT. We controlled for risk factors for FMT failure using Cox regression. We also analyzed the effect of zinc supplementation in individuals with deficiency.

Results: Forty-nine subjects had a normal zinc level, and 31 had a low level (<0.66 µg/mL). CDI recurred in 3/49 (6%) patients with normal zinc and 5/31 (16%) patients with low zinc (HR = 11.327, 95% CI = 2.162-59.336, p=0.004). Among low zinc subjects, 2 of 25 (8%) that received zinc supplements and 3 of 6 (50%) that did not receive zinc supplements had recurrence of CDI (HR = 0.102, 95% CI = 0.015-0.704, p=0.021).

Conclusion: Zinc deficiency was associated with increased CDI recurrence after FMT. Among zinc-deficient patients, supplementation was associated with reduced recurrence. Further study is needed to determine whether zinc deficiency represents a pathophysiologic mechanism and target for therapy.

RevDate: 2018-11-08

Morand A, Cornu F, Dufour JC, et al (2018)

Human bacterial repertoire of the urinary tract: a potential paradigm shift.

Journal of clinical microbiology pii:JCM.00675-18 [Epub ahead of print].

The aim of this article is to review the human repertoire of bacteria already described by culture and metagenomic techniques in urine, and published in the literature. Our study led us to compare this repertoire with other human repertoires available.We followed automatic and manual bibliographical methods and found 562 bacterial species reported in the literature as part of the human urinary microbiota. Of the 562 species, 322 were described only by culture, 101 by both culture and metagenomics, and 139 only by metagenomic. Three hundred and fifty-two species (62.6%) have been associated with at least one case report of human infection, of which 225 (40.0%) have been described as causative agents of urinary tract infection. The urinary tract bacterial repertoire contains 21.4% of the known prokaryotic diversity associated with human beings (464 in common) and share 23.6% species with the human gut microbiota (350 in common, 62.3% of the urine species). Urinary repertoire shares a significant difference in aero-intolerant species compared with gut microbiota (100/562; 17.8% and 505/1484; 34.0% respectively; p<0.001; OR=9.0 [7.0-11.4]). Studies using high-throughput sequencing show a higher proportion of aero-intolerant bacteria in urine (74/240, 30.8%).Most pathogenic bacteria are part of the commensal human urinary tract bacteria and their pathogenicity may occur following any imbalance of this microbiota. The restoration of urinary tract health can occur following a fecal transplantation. The potential gut origin of the human bacterial microbiota has to be explored.

RevDate: 2018-11-07

Ooijevaar RE, Terveer EM, Verspaget HW, et al (2018)

Clinical Application and Potential of Fecal Microbiota Transplantation.

Annual review of medicine [Epub ahead of print].

Fecal microbiota transplantation (FMT) is a well-established treatment for recurrent Clostridioides difficile infection. FMT has become a more readily available and useful new treatment option as a result of stool banks. The current state of knowledge indicates that dysbiosis of the gut microbiota is implicated in several disorders in addition to C. difficile. Randomized controlled studies have shown FMT to be somewhat effective in treating ulcerative colitis, irritable bowel syndrome, and hepatic encephalopathy. In addition, FMT has been beneficial in treating several other conditions, such as the eradication of multidrug-resistant organisms and graft-versus-host disease. We expect that FMT will soon be implemented as a treatment strategy for several new indications, although further studies are needed. Expected final online publication date for the Annual Review of Medicine Volume 70 is January 27, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

RevDate: 2018-11-07

Song JH, YS Kim (2018)

Recurrent Clostridium difficile Infection: Risk Factors, Treatment, and Prevention.

Gut and liver pii:gnl18071 [Epub ahead of print].

The most common cause of antibiotic-associated diarrhea is Clostridium difficile infection (CDI). Recurrent C. difficile infection (rCDI) often occurs after successful treatment of CDI. Due to the increased incidence and the difficulty in treating rCDI, it is becoming an important clinical issue. Identifying risk factors is helpful for early detection, treatment, and prevention of rCDI. Advanced age, use of antibiotics, gastric acid suppression, and infection with a hypervirulent strain are currently regarded as the major risk factors for rCDI. Several treatment modalities, including vancomycin, fidaxomicin, and fecal microbiota transplant (FMT), are suggested for rCDI treatment. However, there is currently no definitive treatment method with sufficient evidence for rCDI. Recent studies have focused on FMT and have shown positive results for rCDI. Prevention of rCDI by measures such as hand washing and isolation of patients is very important. However, these preventive measures are often overlooked in clinical practice. Here, we review the risk factors, treatment, and prevention of rCDI.

RevDate: 2018-11-21

Jiang ZD, Jenq RR, Ajami NJ, et al (2018)

Safety and preliminary efficacy of orally administered lyophilized fecal microbiota product compared with frozen product given by enema for recurrent Clostridium difficile infection: A randomized clinical trial.

PloS one, 13(11):e0205064 pii:PONE-D-18-09615.

BACKGROUND: Fecal microbiota transplantation (FMT) via colonoscopy or enema has become a commonly used treatment of recurrent C. difficile infection (CDI).

AIMS: To compare the safety and preliminary efficacy of orally administered lyophilized microbiota product compared with frozen product by enema.

METHODS: In a single center, adults with ≥ 3 episodes of recurrent CDI were randomized to receive encapsulated lyophilized fecal microbiota from 100-200 g of donor feces (n = 31) or frozen FMT from 100 g of donor feces (n = 34) by enema. Safety during the three months post FMT was the primary study objective. Prevention of CDI recurrence during the 60 days after FMT was a secondary objective. Fecal microbiome changes were examined in first 39 subjects studied.

RESULTS: Adverse experiences were commonly seen in equal frequency in both groups and did not appear to relate to the route of delivery of FMT. CDI recurrence was prevented in 26 of 31 (84%) subjects randomized to capsules and in 30 of 34 (88%) receiving FMT by enema (p = 0.76). Both products normalized fecal microbiota diversity while the lyophilized orally administered product was less effective in repleting Bacteroidia and Verrucomicrobia classes compared to frozen product via enema.

CONCLUSIONS: The route of delivery, oral or rectal, did not influence adverse experiences in FMT. In preliminary evaluation, both routes appeared to show equivalent efficacy, although the dose may need to be higher for lyophilized product. Spore-forming bacteria appear to be the most important engrafting organisms in FMT by the oral route using lyophilized product.

TRIAL REGISTRATION: ClinicalTrials.gov NCT02449174.

RevDate: 2018-11-02

Gopalsamy SN, Woodworth MH, Wang T, et al (2018)

The Use of Microbiome Restoration Therapeutics to Eliminate Intestinal Colonization With Multidrug-Resistant Organisms.

The American journal of the medical sciences, 356(5):433-440.

Antibiotic resistance (AR) has been described by the World Health Organization as an increasingly serious threat to global public health. Many mechanisms of AR have become widespread due to global selective pressures such as widespread antibiotic use. The intestinal tract is an important reservoir for many multidrug-resistant organisms (MDROs), and next-generation sequencing has expanded understanding of the resistome, defined as the comprehensive sum of genetic determinants of AR. Intestinal decolonization has been explored as a strategy to eradicate MDROs with selective digestive tract decontamination and probiotics being notable examples with mixed results. This review focuses on fecal microbiota transplantation and the early evidence supporting its efficacy in decolonizing MDROs and potential mechanisms of action to reduce AR genes. Current evidence suggests that fecal microbiota transplantation may have promise in restoring healthy microbial diversity and reducing AR, and clinical trials are underway to better characterize its safety and efficacy.

RevDate: 2018-11-02

Stripling J, M Rodriguez (2018)

Current Evidence in Delivery and Therapeutic Uses of Fecal Microbiota Transplantation in Human Diseases-Clostridium difficile Disease and Beyond.

The American journal of the medical sciences, 356(5):424-432.

The use of fecal microbiota transplantation (FMT) was first described in China in the 4th century by Ge Hong when "yellow soup," a fecal slurry, was administered for the treatment of severe food poisoning and diarrhea, a practice that continued for centuries. Bedouin groups also consumed stools of their camels as a remedy for dysentery. FMT was also applied in veterinary medicine in Europe in the 16th century. Additional therapeutic use of human excretions was described in Europe in the 18th and 19th century and in World War II, when gut bacteria were administered to German soldiers suffering from dysentery in the North African campaign. More scientifically, Eismann, in 1958, utilized fecal transplantation via enema in 4 patients for the treatment of severe pseudomembranous colitis with success. Following this report a number of isolated cases were published describing the use of FMT by different delivery routes for the treatment of a variety of illnesses.

RevDate: 2018-11-20

Khoruts A (2018)

Targeting the microbiome: from probiotics to fecal microbiota transplantation.

Genome medicine, 10(1):80 pii:10.1186/s13073-018-0592-8.

The modern techniques of microbiome science can be applied to the development and evaluation of all microbiota-directed products, including probiotics and fecal microbiota transplantation.

RevDate: 2018-11-14

Sun W, Guo Y, Zhang S, et al (2018)

Fecal Microbiota Transplantation Can Alleviate Gastrointestinal Transit in Rats with High-Fat Diet-Induced Obesity via Regulation of Serotonin Biosynthesis.

BioMed research international, 2018:8308671.

Aim: We tested the hypothesis that fecal microbiota transplantation (FMT) could regulate the biotransformation of bile acids, such as deoxycholic acid (DCA) and cholic acid (CA), which in turn regulate the biosynthesis of serotonin in the gut and relieve gastrointestinal dysmotility in high-fat diet- (HFD-) induced obesity in rats.

Methods: Male Sprague-Dawley rats were randomly divided into the control diet group, HFD group, and HFD-fed with receiving FMT. HFD was fed for 12 weeks. At the end of two-week HFD, FMT was carried out for two weeks. The gastrointestinal transit, serotonin concentration, the expression of tryptophan hydroxylase 1 (TPH1) and serotonin reuptake transporter (SERT), and the levels of bile acids in intestinal contents were examined.

Results: Compared with the control group, the gastrointestinal transit and small intestinal serotonin concentration of HFD-fed rats were increased. In HFD-fed rats, TPH1 protein expression was increased significantly, while SERT protein expression was decreased, but not significant. The levels of CA and DCA in intestinal contents were also significantly increased in HFD-fed rats compared with the control group. After HFD-fed rats receiving FMT treatment, the gastrointestinal transit, small intestinal serotonin concentration, and TPH1 expression were decreased, while SERT expression was not affected. Moreover, the levels of CA and DCA in intestinal contents were also decreased.

Conclusions: FMT could alleviate small intestinal transit in the HFD-fed rats by regulating the serotonin biosynthesis. In this process, CA and DCA may be related to the regulation of synthesis of serotonin.

RevDate: 2018-10-27

Brunse A, Martin L, Rasmussen TS, et al (2018)

Effect of fecal microbiota transplantation route of administration on gut colonization and host response in preterm pigs.

The ISME journal pii:10.1038/s41396-018-0301-z [Epub ahead of print].

This study examined gut colonization patterns and host responses to fecal microbiota transplantation (FMT) by different administration routes after preterm birth. In two separate experiments, cesarean-delivered, preterm pigs were administered combined oral + rectal, or exclusively rectal donor feces, and compared with saline controls. After 5 days, stomach and colon bacterial compositions were determined by 16S rRNA gene amplicon sequencing, and organic acid metabolites measured. Further, gut pathology, mucosa bacterial adherence, and goblet cell density were assessed. FMT increased the relative abundance of obligate anaerobes in the colon without affecting total bacterial load. Bacteroides colonized recipients despite low abundance in the donor feces, whereas highly abundant Prevotella and Ruminococcaceae did not. Further, FMT changed carbohydrate metabolism from lactate to propionate production thereby increasing colonic pH. Besides, FMT preserved goblet cell mucin stores and reduced necrotizing enterocolitis incidence. Only rectal FMT increased the stomach-to-colon pH gradient and resistance to mucosa bacterial adhesion. Conversely, oral + rectal FMT increased bacterial adhesion, internal organ colonization, and overall mortality. Our results uncovered distinctions in bacterial colonization patterns along the gastrointestinal tract, as well as host tolerability between oral and rectal FMT administration in preterm newborns. Besides, FMT showed the potential to prevent necrotizing enterocolitis.

RevDate: 2018-10-25

Kiouptsi K, Ruf W, C Reinhardt (2018)

Microbiota-Derived Trimethylamine.

Circulation research, 123(10):1112-1114.

RevDate: 2018-11-14

Skye SM, Zhu W, Romano KA, et al (2018)

Microbial Transplantation With Human Gut Commensals Containing CutC Is Sufficient to Transmit Enhanced Platelet Reactivity and Thrombosis Potential.

Circulation research, 123(10):1164-1176.

RATIONALE: Gut microbes influence cardiovascular disease and thrombosis risks through the production of trimethylamine N-oxide (TMAO). Microbiota-dependent generation of trimethylamine (TMA)-the precursor to TMAO-is rate limiting in the metaorganismal TMAO pathway in most humans and is catalyzed by several distinct microbial choline TMA-lyases, including the proteins encoded by the cutC/D (choline utilization C/D) genes in multiple human commensals.

OBJECTIVE: Direct demonstration that the gut microbial cutC gene is sufficient to transmit enhanced platelet reactivity and thrombosis potential in a host via TMA/TMAO generation has not yet been reported.

METHODS AND RESULTS: Herein, we use gnotobiotic mice and a series of microbial colonization studies to show that microbial cutC-dependent TMA/TMAO production is sufficient to transmit heightened platelet reactivity and thrombosis potential in a host. Specifically, we examine in vivo thrombosis potential employing germ-free mice colonized with either high TMA-producing stable human fecal polymcrobial communities or a defined CutC-deficient background microbial community coupled with a CutC-expressing human commensal±genetic disruption of its cutC gene (ie, Clostridium sporogenes Δ cutC).

CONCLUSIONS: Collectively, these studies point to the microbial choline TMA-lyase pathway as a rational molecular target for the treatment of atherothrombotic heart disease.

RevDate: 2018-10-25

Li P, Zhang T, Xiao Y, et al (2018)

Timing for the second fecal microbiota transplantation to maintain the long-term benefit from the first treatment for Crohn's disease.

Applied microbiology and biotechnology pii:10.1007/s00253-018-9447-x [Epub ahead of print].

Increasing evidence has shown that fecal microbiota transplantation (FMT) could be a promising treatment option for Crohn's disease (CD). However, the frequency of FMT for CD treatment remains unclear. This study aimed to evaluate the optimal timing for administering the second course of FMT to maintain the long-term clinical effects from the first FMT for patients with CD. Sixty-nine patients with active CD who underwent FMT twice and benefited from the first FMT were enrolled in this study. Clinical response, stool microbiota, and urine metabolome of patients were assessed during the follow-up. The median time of maintaining clinical response to the first FMT in total 69 patients was 125 days (IQR, 82.5-225.5). The time of maintaining clinical response to the second FMT in 56 of 69 patients was 176.5 days (IQR, 98.5-280). The fecal microbiota composition of each patient post the first FMT was closer to that of his/her donor. Compared to that of the baseline, patients prior to the second course of FMT showed significant differences in urinary metabolic profiles characterized by increased indoxyl sulfate, 4-hydroxyphenylacetate, creatinine, dimethylamine, glycylproline, hippurate, and trimethylamine oxide (TMAO). This study demonstrated that patients with CD could be administered the second course of FMT less than 4 months after the first FMT for maintaining the clinical benefits from the first FMT. This was supported by the host-microbial metabolism changes in patients with active CD. Trial registration: ClinicalTrials.gov , NCT01793831. Registered 18 February 2013. https://clinicaltrials.gov/ct2/show/NCT01793831?term=NCT01793831&rank=1.

RevDate: 2018-10-25

Battaglioli EJ, Hale VL, Chen J, et al (2018)

Clostridioides difficile uses amino acids associated with gut microbial dysbiosis in a subset of patients with diarrhea.

Science translational medicine, 10(464):.

The gut microbiota plays a critical role in pathogen defense. Studies using antibiotic-treated mice reveal mechanisms that increase susceptibility to Clostridioides difficile infection (CDI), but risk factors associated with CDI in humans extend beyond antibiotic use. Here, we studied the dysbiotic gut microbiota of a subset of patients with diarrhea and modeled the gut microbiota of these patients by fecal transplantation into germ-free mice. When challenged with C. difficile, the germ-free mice transplanted with fecal samples from patients with dysbiotic microbial communities showed increased gut amino acid concentrations and greater susceptibility to CDI. A C. difficile mutant that was unable to use proline as an energy source was unable to robustly infect germ-free mice transplanted with a dysbiotic or healthy human gut microbiota. Prophylactic dietary intervention using a low-proline or low-protein diet in germ-free mice colonized by a dysbiotic human gut microbiota resulted in decreased expansion of wild-type C. difficile after challenge, suggesting that amino acid availability might be important for CDI. Furthermore, a prophylactic fecal microbiota transplant in mice with dysbiosis reduced proline availability and protected the mice from CDI. Last, we identified clinical risk factors that could potentially predict gut microbial dysbiosis and thus greater susceptibility to CDI in a retrospective cohort of patients with diarrhea. Identifying at-risk individuals and reducing their susceptibility to CDI through gut microbiota-targeted therapies could be a new approach to preventing C. difficile infection in susceptible patients.

RevDate: 2018-11-14

Lai ZL, Tseng CH, Ho HJ, et al (2018)

Fecal microbiota transplantation confers beneficial metabolic effects of diet and exercise on diet-induced obese mice.

Scientific reports, 8(1):15625 pii:10.1038/s41598-018-33893-y.

Diet and exercise are conventional methods for controlling body weight and are linked to alterations in gut microbiota. However, the associations of diet, exercise, and gut microbiota in the control of obesity remain largely unknown. In the present study, using 16S rRNA amplicon sequencing and fecal microbiota transplantation (FMT), normal fat diet (NFD), exercise and their combination resulted in improved metabolic profiles in comparison to sedentary lifestyle with high fat diet (HFD). Moreover, diet exerted more influence than exercise in shaping the gut microbiota. HFD-fed mice receiving FMT from NFD-exercised donors not only showed remarkably reduced food efficacy, but also mitigated metabolic profiles (p < 0.05). The transmissible beneficial effects of FMT were associated with bacterial genera Helicobacter, Odoribacter and AF12 and overrepresentation of oxidative phosphorylation and glycolysis genes. Our findings demonstrate that the beneficial effects of diet and exercise are transmissible via FMT, suggesting a potential therapeutic treatment for obesity.

RevDate: 2018-11-14

Yodoshi T, TL Hurt (2018)

Fecal Microbiota Transplantation to Patients with Refractory Very Early Onset Ulcerative Colitis.

Pediatric gastroenterology, hepatology & nutrition, 21(4):355-360.

Recently, fecal microbiota transplantation (FMT) has been attracting attention as a possible medical treatment of ulcerative colitis (UC). A randomized controlled trial of FMT for children with UC is currently underway. Therapeutic effects of FMT for adults with UC remain controversial. We report two cases of early-onset UC in children. A patient was diagnosed with UC at age 1-year 9-month and underwent FMT at age 2-year 3-month. He attained clinical remission for three weeks after FMT, but then relapsed at four weeks, ultimately undergoing a total colectomy. Another child was diagnosed with UC at 2-year 10-month and she underwent FMT at age 5 years. She has remained in clinical remission following FMT for 24 months and her UC has been maintained without complications with tacrolimus and azathioprine. We report that FMT for early-onset UC appears to be safe and potentially effective.

RevDate: 2018-11-26

Vallianou NG, Stratigou T, S Tsagarakis (2018)

Microbiome and diabetes: Where are we now?.

Diabetes research and clinical practice, 146:111-118 pii:S0168-8227(18)30913-6 [Epub ahead of print].

Alterations in the diversity or structure of gut microbiota known as dysbiosis, may affect metabolic activities, resulting in metabolic disorders, such as obesity and diabetes. The development of more sophisticated methods, such as metagenomics sequencing, PCR-denaturing gradient gel electrophoresis, microarrays and fluorescence in situ hybridization, has expanded our knowledge on gut microbiome. Dysbiosis has been related to increased plasma concentrations of gut microbiota-derived lipopolysaccharide (LPS), which triggers the production of a variety of cytokines and the recruitment of inflammatory cells. Metabolomics have demonstrated that butyrate and propionate suppress weight gain in mice with high fat diet-induced obesity, and acetate has been proven to reduce food intake in healthy mice. The role of prebiotics, probiotics, genetically modified bacteria and fecal microbiota transplantation, as potential therapeutic challenges for type 2 diabetes will be discussed in this review.

RevDate: 2018-11-15

Elkrief A, Derosa L, Zitvogel L, et al (2018)

The intimate relationship between gut microbiota and cancer immunotherapy.

Gut microbes [Epub ahead of print].

Immunotherapy is widely used to treat a large variety of malignancies and has revolutionized the therapeutic approach to cancer. Major efforts are ongoing to identify biomarkers that predict response to immunotherapy as well as new strategies to improve ICI efficacy and clinical outcomes. Studies have shown that the gut microbiome determines the extent to which ICIs may invigorate the anticancer immune response. Here, the authors review recent studies that have described the effects of the gut microbiota on the efficacy of CTLA-4 and PD-1 inhibitors and outline potential future clinical directions of these findings.

RevDate: 2018-11-14

Chen X, S Devaraj (2018)

Gut Microbiome in Obesity, Metabolic Syndrome, and Diabetes.

Current diabetes reports, 18(12):129 pii:10.1007/s11892-018-1104-3.

PURPOSE OF REVIEW: Obesity and diabetes are worldwide epidemics. There is also a growing body of evidence relating the gut microbiome composition to insulin resistance. The purpose of this review is to delineate the studies linking gut microbiota to obesity, metabolic syndrome, and diabetes.

RECENT FINDINGS: Animal studies as well as proof of concept studies using fecal transplantation demonstrate the pivotal role of the gut microbiota in regulating insulin resistance states and inflammation. While we still need to standardize methodologies to study the microbiome, there is an abundance of evidence pointing to the link between gut microbiome, inflammation, and insulin resistance, and future studies should be aimed at identifying unifying mechanisms.

RevDate: 2018-10-31

Pesce M, Borrelli O, Saliakellis E, et al (2018)

Gastrointestinal Neuropathies: New Insights and Emerging Therapies.

Gastroenterology clinics of North America, 47(4):877-894.

The bewildering complexity of the enteric nervous system makes it susceptible to develop a wide array of motility disorders, collectively called enteric neuropathies. These gastrointestinal conditions are among the most challenging to manage, mainly given poor characterization of their etiopathophysiology and outcomes. Not surprisingly, therefore, targeted or curative therapies for enteric neuropathies are lacking and management is largely symptomatic. Nonetheless, recent advances in neurogastroenterology have witnessed improvements in established strategies, such as intestinal transplantation and the emergence of new treatments including novel drugs, electrical pacing, and manipulation of fecal microbiota, as well as stem cell and gene therapy.

RevDate: 2018-11-20

Wang H, Cui B, Li Q, et al (2018)

The Safety of Fecal Microbiota Transplantation for Crohn's Disease: Findings from A Long-Term Study.

Advances in therapy, 35(11):1935-1944.

INTRODUCTION: Fecal microbiota transplantation (FMT) has been used as a potential treatment option for Crohn's disease (CD). However, there is still lack of safety and efficacy evidence based on large samples of CD undergoing FMT. This study aimed to evaluate the risk factors of adverse event (AE) in the long term and the efficacy of FMT in the short term for patients with CD.

METHODS: FMT via mid-gut for mild to severe CD in a single center trial (NCT01793831) was performed from October 2012 to December 2016. The possible factors with AE and efficacy after FMT were prospectively recorded.

RESULTS: A total of 184 frequencies of FMT were performed for 139 patients who received FMT. During 1 month after FMT, 13.6% of mild AEs occurred, including increased frequency of defecation, fever, abdominal pain, flatulence, hematochezia, vomiturition, bloating and herpes zoster. No AE beyond 1 month was observed. Therefore, a 1 month cut-off could be suggested to define short-term and long-term AEs of FMT. Among the possible risk factors, only fecal microbiota purification methods were closely associated with the occurrence of AEs. The rate of AEs in patients undergoing manual methods for the preparation of fecal microbiota was 21.7%, which was significantly higher than the 8.7% in those experiencing an automatic method. The manual or automatic purification of fecal microbiota had no correlation with the efficacy of FMT.

CONCLUSION: This cohort study based on the largest size of cases demonstrated that improved fecal microbiota preparation reduced the rates of AEs, but did not affect the clinical efficacy in patients with CD.

RevDate: 2018-11-14

Li J, Cui H, Cai Y, et al (2018)

Tong-Xie-Yao-Fang Regulates 5-HT Level in Diarrhea Predominant Irritable Bowel Syndrome Through Gut Microbiota Modulation.

Frontiers in pharmacology, 9:1110.

Tong-Xie-Yao-Fang (TXYF) has been widely used for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) in traditional Chinese medicine. However, its mechanism of action in the treatment of IBS-D remains to be fully understood. Recent reports have shown that Clostridium species in the gut can induce 5-HT production in the colon, which then contributes to IBS-D. Due to the wide use of TXYF in the clinical treatment of IBS-D and the close relationship between gut microbiota and IBS-D, we hypothesize that TXYF treats IBS-D by modulating gut microbiota and regulating colonic 5-HT levels. In this study, variation analysis of 16S rRNA was conducted to evaluate changes in the distribution of gut microbiota in IBS-D model rats after TXYF treatment. Moreover, we investigated whether TXYF could affect colonic 5-HT levels in IBS-D model rats. We then performed fecal transplantation experiments to confirm the effects of TXYF on gut microbiota and 5-HT levels. We found that TXYF treatment can ameliorate IBS-D and regulate 5-HT levels in colon tissue homogenates. TXYF treatment also affected the diversity of gut microbiota and altered the relative abundance of Akkermansia and Clostridium sensu stricto 1 in gut flora populations. Finally, we showed that fecal transplantation from TXYF-treated rats could relieve IBS-D and regulate 5-HT levels in colon tissue homogenates. In conclusion, the present study demonstrates that TXYF treatment diminishes colonic 5-HT levels and alleviates the symptoms of IBS-D by favorably affecting microbiota levels in gut flora communities.

RevDate: 2018-10-15

Cho S, Spencer E, Hirten R, et al (2018)

Fecal Microbiota Transplant for Recurrent Clostridium Difficile Infection in Pediatric Inflammatory Bowel Disease.

Journal of pediatric gastroenterology and nutrition [Epub ahead of print].

OBJECTIVES: Recurrent Clostridium difficile infection (RCDI) increases morbidity and mortality in patients with inflammatory bowel disease (IBD). Fecal microbiota transplant (FMT) is known to be very effective for RCDI in non-IBD patients with cure rates up to 91%. The same success rates of FMT have not been reported in IBD patients with RCDI, and the data in pediatrics is limited. We aimed to determine the effectiveness of FMT for RCDI in established pediatric IBD patients.

METHODS: We performed a retrospective chart review of pediatric patients with IBD and RCDI (≥3 episodes) who underwent FMT via colonoscopy at a tertiary care IBD center. The primary outcome was the rate of RCDI within 60 days post-FMT. The secondary outcomes were recurrence rate by 6 months, rate of colectomy, and time to recurrence.

RESULTS: Of the 8 eligible patients, 6 had ulcerative colitis, 1 had IBD-unspecified, and 1 had Crohn's disease. Median [interquartile range] age was 13 [11-14] years. All patients were on vancomycin at FMT. Two patients (25%) had RCDI by 60 days post-FMT and another 3 patients had RCDI between 60 days and 6 months. The median time to recurrence was 101 [40-139] days. Two patients (25%) who developed recurrence went to colectomy after FMT.

CONCLUSIONS: With a cure rate of 75% at 60 days, FMT administered for the treatment of RCDI may be an effective treatment option in pediatric IBD. However, there appears to be a significant rate of late recurrence of CDI after 60 days in these patients.

RevDate: 2018-11-14

Cheng S, Ma X, Geng S, et al (2018)

Fecal Microbiota Transplantation Beneficially Regulates Intestinal Mucosal Autophagy and Alleviates Gut Barrier Injury.

mSystems, 3(5): pii:mSystems00137-18.

Fecal microbiota transplantation (FMT) is one of the most effective ways to regulate the gut microbiota. Here, we investigated the effect of exogenous fecal microbiota on gut function from the perspective of analysis of the mucosal proteomes in a piglet model. A total of 289 differentially expressed proteins were annotated with 4,068 gene ontology (GO) function entries in the intestinal mucosa, and the levels of autophagy-related proteins in the forkhead box O (FoxO) signaling pathway were increased whereas the levels of proteins related to inflammation response were decreased in the recipient. Then, to assess the alleviation of epithelial injury in the Escherichia coli K88-infected piglets following FMT, intestinal microbiome-metabolome responses were determined. 16S rRNA gene sequencing showed that the abundances of beneficial bacteria, such as Lactobacillus and Succinivibrio, were increased whereas those of Enterobacteriaceae and Proteobacteria bacteria were decreased in the infected piglets following FMT. Metabolomic analysis revealed that levels of 58 metabolites, such as lactic acid and succinic acid, were enhanced in the intestinal lumen and that seven metabolic pathways, such as branched-chain amino acid metabolism pathways, were upregulated in the infected piglets following FMT. In concordance with the metabolome data, results of metagenomics prediction analysis also demonstrated that FMT modulated the metabolic functions of gut microbiota associated with linoleic acid metabolism. In addition, intestinal morphology was improved, a result that coincided with the decrease of intestinal permeability and the enhancement of mucins and mucosal expression of tight junction proteins in the recipient. Taken together, the results showed that FMT triggered intestinal mucosal protective autophagy and alleviated gut barrier injury through alteration of the gut microbial structure. IMPORTANCE The gut microbiota plays a crucial role in human and animal health, and its disorder causes multiple diseases. Over the past decade, FMT has gained increasing attention due to the success in treating Clostridium difficile infection (CDI) and inflammatory bowel disease (IBD). Although FMT appears to be effective, how FMT functions in the recipient remains unknown. Whether FMT exerts this beneficial effect through a series of changes in the host organism caused by alteration of gut microbial structure is also not known. In the present study, newborn piglets and E. coli K88-infected piglets were selected as models to explore the interplay between host and gut microbiota following FMT. Our results showed that FMT triggered intestinal mucosal autophagy and alleviated gut barrier injury caused by E. coli K88. This report provides a theoretical basis for the use of FMT as a viable therapeutic method for gut microbial regulation.

RevDate: 2018-11-14

Qi X, Li X, Zhao Y, et al (2018)

Treating Steroid Refractory Intestinal Acute Graft-vs.-Host Disease With Fecal Microbiota Transplantation: A Pilot Study.

Frontiers in immunology, 9:2195.

Patients with steroid refractory gastrointestinal (GI) tract graft- vs.-host disease (GvHD) face a poor prognosis and limited therapeutic options. To accurately assess the efficacy and safety of fecal microbiota transplantation (FMT) in treating steroid refractory GI tract GvHD, we conducted a pilot study involving eight patients. Having received FMTs, all patients' clinical symptoms relieved, bacteria enriched, and microbiota composition reconstructed. Compared to those who did not receive FMT, these eight patients achieved a higher progression-free survival. FMT can serve as a therapeutic option for GI tract aGVHD, but its effectiveness and safety need further evaluations. Clinical Trial Registration: NCT03148743.

RevDate: 2018-11-14

Zuo T, SC Ng (2018)

The Gut Microbiota in the Pathogenesis and Therapeutics of Inflammatory Bowel Disease.

Frontiers in microbiology, 9:2247.

In the twenty first century, the changing epidemiology of inflammatory bowel disease (IBD) globally with increasing disease incidence across many countries relates to the altered gut microbiota, due to a combinatorial effect of environmental factors, human immune responses and genetics. IBD is a gastrointestinal disease associated with a gut microbial dysbiosis, including an expansion of facultative anaerobic bacteria of the family Enterobacteriaceae. Advances in high-throughput sequencing enable us to entangle the gut microbiota in human health and IBD beyond the gut bacterial microbiota, expanding insights into the mycobiota, virobiota and helminthes. Caudovirales (viruses) and Basidiomycota, Ascomycota, and Candida albicans (fungi) are revealed to be increased in IBD. The deconvolution of the gut microbiota in IBD lays the basis for unveiling the roles of these various gut microbiota components in IBD pathogenesis and being conductive to instructing on future IBD diagnosis and therapeutics. Here we comprehensively elucidate the alterations in the gut microbiota in IBD, discuss the effect of diets in the gut microbiota in relation to IBD, and illustrate the potential of manipulation of gut microbiota for IBD therapeutics. The therapeutic strategy of antibiotics, prebiotics, probiotics and fecal microbiota transplantation will benefit the effective application of precision microbiome manipulation in IBD.

RevDate: 2018-11-14

Camara-Lemarroy CR, Metz LM, VW Yong (2018)

Focus on the gut-brain axis: Multiple sclerosis, the intestinal barrier and the microbiome.

World journal of gastroenterology, 24(37):4217-4223.

The brain-gut axis serves as the bidirectional connection between the gut microbiome, the intestinal barrier and the immune system that might be relevant for the pathophysiology of inflammatory demyelinating diseases. People with multiple sclerosis have been shown to have an altered microbiome, increased intestinal permeability and changes in bile acid metabolism. Experimental evidence suggests that these changes can lead to profound alterations of peripheral and central nervous system immune regulation. Besides being of pathophysiological interest, the brain-gut axis could also open new avenues of therapeutic targets. Modification of the microbiome, the use of probiotics, fecal microbiota transplantation, supplementation with bile acids and intestinal barrier enhancers are all promising candidates. Hopefully, pre-clinical studies and clinical trials will soon yield significant results.

RevDate: 2018-11-14

Fang H, Fu L, J Wang (2018)

Protocol for Fecal Microbiota Transplantation in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

BioMed research international, 2018:8941340.

Background: Fecal microbiota transplantation (FMT) is an emerging treatment approach for inflammatory bowel disease (IBD). The donor selection, the separation of fecal bacteria, the frequency of FMT, the way of infusion, the long-term safety, and efficacy are still uncertain.

Aim: To further study the efficacy and safety and protocol of FMT for IBD.

Methods: A systematic review and meta-analysis were conducted until February, 2018. Clinical remission was established as the primary outcome.

Results: A total of 596 paediatric and adult IBD patients were enrolled, and 459 patients received FMT therapy. 28.8% (132/459) patients achieved clinical remission during follow-up. 53% (241/459) patients achieved clinical response. The pooled estimated clinical remission for ulcerative colitis (UC) was 21% (95% CI: 8%-37%) and 30% (95% CI: 11%-52%) for Crohn's disease (CD), both with a risk of heterogeneity; 10% (95% CI: 0%-43%) for paediatric UC; 26% (95% CI: 10%-48%) for adult UC; 45% for paediatric CD (95% CI: 24%-66%); 22% (95% CI: 3%-52%) for adult CD. Meta-analysis of cohort studies showed that moderate-severe IBD patients could achieve more significant remission from FMT than mild-moderate patients (P=0.037). Delivery route has no impact on the efficacy of FMT in UC and CD. Based on current available evidence, a trend was observed towards higher clinical remission rate of frozen stool FMT than that of fresh stool for UC, while there was no significant difference between fresh and frozen FMT for CD. The optimal donor stool for FMT is still uncertain. Meta-analysis of RCTs showed that FMT treatment achieved significantly higher clinical remission rate than placebo for UC (28% versus 9%, P=0.0003).

Conclusion: FMT is an effective and safe therapy for both paediatric and adult IBD; fresh or frozen donor stool, delivery route, and antibiotic pretreatment or not have no impact on the efficacy of FMT in IBD. FMT might be a potential rescue therapy and even an initial standardized therapy for IBD. However, few data exist on long-term safety and efficacy and further validation is needed.

RevDate: 2018-10-10

Paule A, Frezza D, M Edeas (2018)

Microbiota and Phage Therapy: Future Challenges in Medicine.

Medical sciences (Basel, Switzerland), 6(4): pii:medsci6040086.

An imbalance of bacterial quantity and quality of gut microbiota has been linked to several pathologies. New strategies of microbiota manipulation have been developed such as fecal microbiota transplantation (FMT); the use of pre/probiotics; an appropriate diet; and phage therapy. The presence of bacteriophages has been largely underestimated and their presence is a relevant component for the microbiome equilibrium. As a promising treatment, phage therapy has been extensively used in Eastern Europe to reduce pathogenic bacteria and has arisen as a new method to modulate microbiota diversity. Phages have been selected and "trained" to infect a wide spectrum of bacteria or tailored to infect specific antibiotic resistant bacteria present in patients. The new development of genetically modified phages may be an efficient tool to treat the gut microbiota dysbiosis associated with different pathologies and increased production of bacterial metabolites and subsequently decrease systemic low-grade chronic inflammation associated with chronic diseases. Microbiota quality and mitochondria dynamics can be remodulated and manipulated by phages to restore the equilibrium and homeostasis of the system. Our aim is to highlight the great interest for phages not only to eliminate and control pathogenic bacterial infection but also in the near future to modulate the microbiota by adding new functions to selected bacteria species and rebalance the dynamic among phages and bacteria. The challenge for the medicine of tomorrow is to re-think and redesign strategies differently and far from our traditional thinking.

RevDate: 2018-10-09

Paknikar R, J Pekow (2018)

Fecal Microbiota Transplantation for the Management of Clostridium difficile Infection.

Surgical infections [Epub ahead of print].

The clinical burden of Clostridium difficile infection (CDI) continues to grow. Despite the multitude of treatment options that have been developed and tested to combat the morbidity and death associated with CDI, recurrence remains common. As such, treatment modalities such as fecal microbiota transplantation (FMT) have become studied increasingly; FMT serves to transplant stool from carefully selected healthy subjects into C. difficile positive patients through a variety of delivery routes. In doing so, FMT is hypothesized to correct dysbiosis of the recipient gut microbiome addressing the root cause of the pathogenesis of C. difficile infection. A growing body of evidence shows FMT to be efficacious in this setting, and the study of FMT accordingly continues to evolve to identify novel indications for its utilization.

RevDate: 2018-11-14
CmpDate: 2018-10-23

Wen W, Zhang H, Shen J, et al (2018)

Fecal microbiota transplantation for patients with irritable bowel syndrome: A meta-analysis protocol.

Medicine, 97(40):e12661.

Irritable bowel syndrome (IBS) is a common functional bowel disease characterized by chronic or recurrent abdominal pain, bloating, constipation, and diarrhea. Many patients with IBS have a poor quality of life due to abdominal discomfort, diarrhea, constipation, and the presence of other diseases. At present, intestinal motility inhibitors, adsorbents, astringents, intestinal mucosal protective agents, and antidepressants have been combined to treat IBS, but the treatment process is long, which results in a large economic burden to patients. Fecal microbiota transplantation (FMT) is a treatment involving the transplantation of functional bacteria from healthy human feces into the gastrointestinal tract of patients; thus, replacing the intestinal flora and modulating intestinal and extra-intestinal diseases. In recent years, the efficacy and economic benefits of FMT in the treatment of IBS have received increasing attention from researchers.A search for randomized controlled trials (RCTs) on treating IBS with FMT will be performed using 9 databases, including PubMed, the Cochrane Library, Embase, ClinicalTrails, China National Knowledge Infrastructure, Sino Med, ScienceDirect, VIP, and Wanfang Data. Two reviewers will independently screen data extraction studies and assess study quality and risk of bias. The risk of bias for each RCT will be assessed against the Cochrane Handbook standards to assess methodological quality. RevMan V.5.3 software will be used to calculate data synthesis when meta-analysis is allowed.This study will provide a high-quality synthesis of existing evidence on the effectiveness and safety of FMT in the treatment of IBS.This study will determine if FMT is an effective and safe intervention for IBS.PROSPERO registration number is PROSPERO CRD42018108080.

RevDate: 2018-10-04

Warner BB (2018)

The contribution of the gut microbiome to neurodevelopment and neuropsychiatric disorders.

Pediatric research pii:10.1038/s41390-018-0191-9 [Epub ahead of print].

Bidirectional communication between the gut and brain is well recognized, with data now accruing for a specific role of the gut microbiota in that link, referred to as the microbiome-gut-brain axis. This review will discuss the emerging role of the gut microbiota in brain development and behavior. Animal studies have clearly demonstrated effects of the gut microbiota on gene expression and neurochemical metabolism impacting behavior and performance. Based on these changes, a modulating role of the gut microbiota has been demonstrated for a variety of neuropsychiatric disorders, including depression, anxiety, and movement including Parkinson's, and importantly for the pediatric population autism. Critical developmental windows that influence early behavioral outcomes have been identified that include both the prenatal environment and early postnatal colonization periods. The clearest data regarding the role of the gut microbiota on neurodevelopment and psychiatric disorders is from animal studies; however, human data have begun to emerge, including an association between early colonization patterns and cognition. The importance of understanding the contribution of the gut microbiota to the development and functioning of the nervous system lies in the potential to intervene using novel microbial-based approaches to treating neurologic conditions. While pathways of communication between the gut and brain are well established, the gut microbiome is a new component of this axis. The way in which organisms that live in the gut influence the central nervous system (CNS) and host behavior is likely to be multifactorial in origin. This includes immunologic, endocrine, and metabolic mechanisms, all of which are pathways used for other microbial-host interactions. Germ-free (GF) mice are an important model system for understanding the impact of gut microbes on development and function of the nervous system. Alternative animal model systems have further clarified the role of the gut microbiota, including antibiotic treatment, fecal transplantation, and selective gut colonization with specific microbial organisms. Recently, researchers have started to examine the human host as well. This review will examine the components of the CNS potentially influenced by the gut microbiota, and the mechanisms mediating these effects. Links between gut microbial colonization patterns and host behavior relevant to a pediatric population will be examined, highlighting important developmental windows in utero or early in development.

RevDate: 2018-11-22

Bromberg JS, Hittle L, Xiong Y, et al (2018)

Gut microbiota-dependent modulation of innate immunity and lymph node remodeling affects cardiac allograft outcomes.

JCI insight, 3(19): pii:121045 [Epub ahead of print].

We hypothesized that the gut microbiota influences survival of murine cardiac allografts through modulation of immunity. Antibiotic pretreated mice received vascularized cardiac allografts and fecal microbiota transfer (FMT), along with tacrolimus immunosuppression. FMT source samples were from normal, pregnant (immune suppressed), or spontaneously colitic (inflammation) mice. Bifidobacterium pseudolongum (B. pseudolongum) in pregnant FMT recipients was associated with prolonged allograft survival and lower inflammation and fibrosis, while normal or colitic FMT resulted in inferior survival and worse histology. Transfer of B. pseudolongum alone resulted in reduced inflammation and fibrosis. Stimulation of DC and macrophage lines with B. pseudolongum induced the antiinflammatory cytokine IL-10 and homeostatic chemokine CCL19 but induced lesser amounts of the proinflammatory cytokines TNFα and IL-6. In contrast, LPS and Desulfovibrio desulfuricans (D. desulfuricans), more abundant in colitic FMT, induced a more inflammatory cytokine response. Analysis of mesenteric and peripheral lymph node structure showed that B. pseudolongum gavage resulted in a higher laminin α4/α5 ratio in the lymph node cortical ridge, indicative of a suppressive environment, while D. desulfuricans resulted in a lower laminin α4/α5 ratio, supportive of inflammation. Discrete gut bacterial species alter immunity and may predict graft outcomes through stimulation of myeloid cells and shifts in lymph node structure and permissiveness.

RevDate: 2018-11-14

Li X, Li Z, Chang Y, et al (2018)

Successful transplantation of guinea pig gut microbiota in mice and its effect on pneumonic plague sensitivity.

PeerJ, 6:e5637 pii:5637.

Microbiota-driven variations in the inflammatory response are predicted to regulate host responses to infection. Increasing evidence indicates that the gastrointestinal and respiratory tracts have an intimate relationship with each other. Gut microbiota can influence lung immunity whereby gut-derived injurious factors can reach the lungs and systemic circulation via the intestinal lymphatics. The intestinal microbiota's ability to resist colonization can be extended to systemic infections or to pathogens infecting distant sites such as the lungs. Unlike the situation with large mammals, the microtus Yersinia pestis 201 strain exhibits strong virulence in mice, but nearly no virulence to large mammals (such as guinea pigs). Hence, to assess whether the intestinal microbiota from guinea pigs was able to affect the sensitivity of mice to challenge infection with the Y. pestis 201 strain, we fed mice with guinea pig diets for two months, after which they were administered 0.5 ml of guinea pig fecal suspension for 30 days by oral gavage. The stools from each mouse were collected on days 0, 15, and 30, DNA was extracted from them, and 16S rRNA sequencing was performed to assess the diversity and composition of the gut microbiota. We found that the intestinal microbiota transplants from the guinea pigs were able to colonize the mouse intestines. The mice were then infected with Yersinia pestis 201 by lung invasion, but no statistical difference was found in the survival rates of the mice that were colonized with the guinea pig's gut microbiota and the control mice. This indicates that the intestinal microbiota transplantation from the guinea pigs did not affect the sensitivity of the mice to pneumonic plague.

RevDate: 2018-11-14

Liang S, Wu X, F Jin (2018)

Gut-Brain Psychology: Rethinking Psychology From the Microbiota-Gut-Brain Axis.

Frontiers in integrative neuroscience, 12:33.

Mental disorders and neurological diseases are becoming a rapidly increasing medical burden. Although extensive studies have been conducted, the progress in developing effective therapies for these diseases has still been slow. The current dilemma reminds us that the human being is a superorganism. Only when we take the human self and its partner microbiota into consideration at the same time, can we better understand these diseases. Over the last few centuries, the partner microbiota has experienced tremendous change, much more than human genes, because of the modern transformations in diet, lifestyle, medical care, and so on, parallel to the modern epidemiological transition. Existing research indicates that gut microbiota plays an important role in this transition. According to gut-brain psychology, the gut microbiota is a crucial part of the gut-brain network, and it communicates with the brain via the microbiota-gut-brain axis. The gut microbiota almost develops synchronously with the gut-brain, brain, and mind. The gut microbiota influences various normal mental processes and mental phenomena, and is involved in the pathophysiology of numerous mental and neurological diseases. Targeting the microbiota in therapy for these diseases is a promising approach that is supported by three theories: the gut microbiota hypothesis, the "old friend" hypothesis, and the leaky gut theory. The effects of gut microbiota on the brain and behavior are fulfilled by the microbiota-gut-brain axis, which is mainly composed of the nervous pathway, endocrine pathway, and immune pathway. Undoubtedly, gut-brain psychology will bring great enhancement to psychology, neuroscience, and psychiatry. Various microbiota-improving methods including fecal microbiota transplantation, probiotics, prebiotics, a healthy diet, and healthy lifestyle have shown the capability to promote the function of the gut-brain, microbiota-gut-brain axis, and brain. It will be possible to harness the gut microbiota to improve brain and mental health and prevent and treat related diseases in the future.

RevDate: 2018-11-24

Krajicek E, Fischer M, Allegretti JR, et al (2018)

Nuts and Bolts of Fecal Microbiota Transplantation.

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association pii:S1542-3565(18)31020-6 [Epub ahead of print].

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RevDate: 2018-09-28

Martinez C, Edwards J, A Hassoun (2018)

Commercialized fecal microbiota transplantation provides efficacious treatment of Clostridium difficile infection.

Infectious diseases (London, England) [Epub ahead of print].

RevDate: 2018-09-27

Taur Y, Coyte K, Schluter J, et al (2018)

Reconstitution of the gut microbiota of antibiotic-treated patients by autologous fecal microbiota transplant.

Science translational medicine, 10(460):.

Antibiotic treatment can deplete the commensal bacteria of a patient's gut microbiota and, paradoxically, increase their risk of subsequent infections. In allogeneic hematopoietic stem cell transplantation (allo-HSCT), antibiotic administration is essential for optimal clinical outcomes but significantly disrupts intestinal microbiota diversity, leading to loss of many beneficial microbes. Although gut microbiota diversity loss during allo-HSCT is associated with increased mortality, approaches to reestablish depleted commensal bacteria have yet to be developed. We have initiated a randomized, controlled clinical trial of autologous fecal microbiota transplantation (auto-FMT) versus no intervention and have analyzed the intestinal microbiota profiles of 25 allo-HSCT patients (14 who received auto-FMT treatment and 11 control patients who did not). Changes in gut microbiota diversity and composition revealed that the auto-FMT intervention boosted microbial diversity and reestablished the intestinal microbiota composition that the patient had before antibiotic treatment and allo-HSCT. These results demonstrate the potential for fecal sample banking and posttreatment remediation of a patient's gut microbiota after microbiota-depleting antibiotic treatment during allo-HSCT.

RevDate: 2018-11-14

Hughes HK, Rose D, P Ashwood (2018)

The Gut Microbiota and Dysbiosis in Autism Spectrum Disorders.

Current neurology and neuroscience reports, 18(11):81 pii:10.1007/s11910-018-0887-6.

PURPOSE OF REVIEW: There is a growing body of evidence indicating the gut microbiota influence neurodevelopment and behavior. The purposes of this review are to provide an overview of studies analyzing the microbiota and their metabolites in autism spectrum disorders (ASD) and to discuss the possible mechanisms of action involved in microbial influence on the brain and behavior.

RECENT FINDINGS: The microbiota-gut-brain (MGB) axis has been extensively studied in animal models, and it is clear that alterations in the composition of microbiota alter neurological and behavioral outcomes. However, findings in human studies are less abundant. Although there are several studies so far showing altered microbiota (dysbiosis) in ASD, the results are heterogeneous and often contradictory. Intervention studies such as fecal microbiota transplant therapies show promise and lend credence to the involvement of the microbiota in ASD. A role for the microbiota in ASD is likely; however, further studies elucidating microbial or metabolomic signatures and mechanisms of action are needed. Future research should focus on intervention studies that can identify specific metabolites and immune mediators that improve with treatment to help identify etiologies and pathological mechanisms of ASD.

RevDate: 2018-11-14

Haak BW, Prescott HC, WJ Wiersinga (2018)

Therapeutic Potential of the Gut Microbiota in the Prevention and Treatment of Sepsis.

Frontiers in immunology, 9:2042.

Alongside advances in understanding the pathophysiology of sepsis, there have been tremendous strides in understanding the pervasive role of the gut microbiota in systemic host resistance. In pre-clinical models, a diverse and balanced gut microbiota enhances host immunity to both enteric and systemic pathogens. Disturbance of this balance increases susceptibility to sepsis and sepsis-related organ dysfunction, while restoration of the gut microbiome is protective. Patients with sepsis have a profoundly distorted composition of the intestinal microbiota, but the impact and therapeutic potential of the microbiome is not well-established in human sepsis. Modulation of the microbiota consists of either resupplying the pool of beneficial microbes by administration of probiotics, improving the intestinal microenvironment to enhance the growth of beneficial species by dietary interventions and prebiotics, or by totally recolonizing the gut with a fecal microbiota transplantation (FMT). We propose that there are three potential opportunities to utilize these treatment modalities over the course of sepsis: to decrease sepsis incidence, to improve sepsis outcome, and to decrease late mortality after sepsis. Exploring these three avenues will provide insight into how disturbances of the microbiota can predispose to, or even perpetuate the dysregulated immune response associated with this syndrome, which in turn could be associated with improved sepsis management.

RevDate: 2018-11-15
CmpDate: 2018-11-15

Plantamura E, Dzutsev A, Chamaillard M, et al (2018)

MAVS deficiency induces gut dysbiotic microbiota conferring a proallergic phenotype.

Proceedings of the National Academy of Sciences of the United States of America, 115(41):10404-10409.

Prominent changes in the gut microbiota (referred to as "dysbiosis") play a key role in the development of allergic disorders, but the underlying mechanisms remain unknown. Study of the delayed-type hypersensitivity (DTH) response in mice contributed to our knowledge of the pathophysiology of human allergic contact dermatitis. Here we report a negative regulatory role of the RIG-I-like receptor adaptor mitochondrial antiviral signaling (MAVS) on DTH by modulating gut bacterial ecology. Cohousing and fecal transplantation experiments revealed that the dysbiotic microbiota of Mavs-/- mice conferred a proallergic phenotype that is communicable to wild-type mice. DTH sensitization coincided with increased intestinal permeability and bacterial translocation within lymphoid organs that enhanced DTH severity. Collectively, we unveiled an unexpected impact of RIG-I-like signaling on the gut microbiota with consequences on allergic skin disease outcome. Primarily, these data indicate that manipulating the gut microbiota may help in the development of therapeutic strategies for the treatment of human allergic skin pathologies.

RevDate: 2018-11-14

Shogbesan O, Poudel DR, Victor S, et al (2018)

A Systematic Review of the Efficacy and Safety of Fecal Microbiota Transplant for Clostridium difficile Infection in Immunocompromised Patients.

Canadian journal of gastroenterology & hepatology, 2018:1394379.

Background: Fecal microbiota transplantation (FMT) has been shown to be effective in recurrent Clostridium difficile (CD) infection, with resolution in 80% to 90% of patients. However, immunosuppressed patients were often excluded from FMT trials, so safety and efficacy in this population are unknown.

Methods: We searched MEDLINE and EMBASE for English language articles published on FMT for treatment of CD infection in immunocompromised patients (including patients on immunosuppressant medications, patients with human immunodeficiency virus (HIV), inherited or primary immunodeficiency syndromes, cancer undergoing chemotherapy, or organ transplant, including-bone marrow transplant) of all ages. We excluded inflammatory bowel disease patients that were not on immunosuppressant medications. Resolution and adverse event rates (including secondary infection, rehospitalization, and death) were calculated.

Results: Forty-four studies were included, none of which were randomized designs. A total of 303 immunocompromised patients were studied. Mean patient age was 57.3 years. Immunosuppressant medication use was the reason for the immunocompromised state in the majority (77.2%), and 19.2% had greater than one immunocompromising condition. Seventy-six percent were given FMT via colonoscopy. Of the 234 patients with reported follow-up outcomes, 207/234 (87%) reported resolution after first treatment, with 93% noting success after multiple treatments. There were 2 reported deaths, 2 colectomies, 5 treatment-related infections, and 10 subsequent hospitalizations.

Conclusion: We found evidence that supports the use of FMT for treatment of CD infection in immunocompromised patients, with similar rates of serious adverse events to immunocompetent patients.

RevDate: 2018-11-14

Fortier LC (2018)

Bacteriophages Contribute to Shaping Clostridioides (Clostridium) difficile Species.

Frontiers in microbiology, 9:2033.

Bacteriophages (phages) are bacterial viruses that parasitize bacteria. They are highly prevalent in nature, with an estimated 1031 viral particles in the whole biosphere, and they outnumber bacteria by at least 10-fold. Hence, phages represent important drivers of bacterial evolution, although our knowledge of the role played by phages in the mammalian gut is still embryonic. Several pathogens owe their virulence to the integrated phages (prophages) they harbor, which encode diverse virulence factors such as toxins. Clostridioides (Clostridium) difficile is an important opportunistic pathogen and several phages infecting this species have been described over the last decade. However, their exact contribution to the biology and virulence of this pathogen remains elusive. Current data have shown that C. difficile phages can alter virulence-associated phenotypes, in particular toxin production, by interfering with bacterial regulatory circuits through crosstalk with phage proteins for example. One phage has also been found to encode a complete binary toxin locus. Multiple regulatory genes have also been identified in phage genomes, suggesting that their impact on the host can be complex and often subtle. In this minireview, the current state of knowledge, major findings, and pending questions regarding C. difficile phages will be presented. In addition, with the apparent role played by phages in the success of fecal microbiota transplantation and the perspective of phage therapy for treatment of recurrent C. difficile infection, it has become even more crucial to understand what C. difficile phages do in the gut, how they impact their host, and how they influence the epidemiology and evolution of this clinically important pathogen.

RevDate: 2018-09-20

Lu M, Z Wang (2018)

Microbiota and Aging.

Advances in experimental medicine and biology, 1086:141-156.

The human gut microbiota is a huge ecosystem that provides lots of functions for host development, immune system, and metabolism. Gut microbiota is linked to lots of diseases, including human metabolic diseases such as obesity, type 2 diabetes (T2D), irritable bowel syndrome, and cardiovascular disease (CVD). Few studies, however, have noted the relationship between aging and microbiota; the connection between aging and microbiota remains largely to be researched. In this review, recent research findings are summarized on the role of gut microbiota in aging processes with emphasis on therapeutic potential of microbiome-targeted interventions in antiaging medicine.

RevDate: 2018-11-14

Staley C, Kaiser T, Vaughn BP, et al (2018)

Predicting recurrence of Clostridium difficile infection following encapsulated fecal microbiota transplantation.

Microbiome, 6(1):166 pii:10.1186/s40168-018-0549-6.

BACKGROUND: Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (rCDI). The use of freeze-dried, encapsulated donor material for FMT (cap-FMT) allows for an easy route of administration and remains clinically effective in the majority of rCDI patients. We hypothesized that specific shifts in the microbiota in response to cap-FMT could predict clinical outcome. We further evaluated the degree of donor microbiota engraftment to determine the extent that donor transfer contributed to recovery.

RESULTS: In total, 89 patients were treated with 100 separate cap-FMTs, with a success rate (no rCDI 60 days post cap-FMT) of 80%. Among responders, the lower alpha diversity (ANOVA P < 0.05) observed among patient's pre-FMT samples was restored following cap-FMT. At 1 week post-FMT, community composition varied by clinical outcome (ANOSIM P < 0.001), with similar abundances among families (Lachnospiraceae, Ruminococcaceae, and Bacteroidaceae) in responder and donor samples. Families that showed differential abundances by outcome (response vs. recurrence) from samples collected 7 days following cap-FMT were used to construct a regression tree-based model to predict recurrence. Results showed a training accuracy of 100% to predict recurrence and the model was 97% accurate against a test data set of samples collected 8-20 days following cap-FMT. Evaluation of the extent of engraftment using the Bayesian algorithm SourceTracker revealed that approximately 50% of the post-FMT communities of responders were attributable to donor microbiota, while an additional 20-30% of the communities were similar to a composite healthy microbiota consisting of all donor samples.

CONCLUSIONS: Regression tree-based analyses of microbial communities identified taxa significantly related to clinical response after 7 days, which can be targeted to improve microbial therapeutics. Furthermore, reinstatement of a healthy assemblage following cap-FMT was only partially attributable to explicit donor engraftment and continued to develop towards an overall healthy assemblage, independent of donor.

RevDate: 2018-09-18

Drastich P, Bajer L, M Kverka (2018)

Possibilities of therapeutic manipulation of the gut microbiota.

Vnitrni lekarstvi, 64(6):665-671.

Human gut microbiota, complex ecosystem of microbes associated with human gut, is essential for the development of the host's immune system and many other physiological functions. Recently, numerous diseases and syndromes were associated with disruption of this ecosystem thus stressing its importance in maintaining the host's health. Growing evidence suggests that by manipulating the gut microbiota, some of these diseases could be treated or even prevented. These manipulations include changes in diet, use of probiotics, prebiotics, antibiotics and fecal microbiota transplantation (FMT). The successes in FMT treatment of recurrent infection of Clostridium difficile led recently to a great interest in extending this treatment modality to other diseases with proven disruption of gut microbiota, such as ulcerative colitis or metabolic syndrome. Key words: Clostridium difficile - dysbiosis - fecal microbial transplantation - microbiota - prebiotics - probiotics.

RevDate: 2018-11-20

Reigadas E, Olmedo M, Valerio M, et al (2018)

Fecal microbiota transplantation for recurrent Clostridium difficile infection: Experience, protocol, and results.

Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia, 31(5):411-418.

OBJECTIVE: Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridium difficile infection (R-CDI). Despite its excellent efficacy, it is still not a routine procedure in most European centers. FMT has not been widely used in Spain to date. We describe our experience with FMT, including a novel approach based on oral fecal capsules.

METHODS: We analyzed a prospectively recorded case series of patients with R-CDI treated with FMT at a single center (June 2014-July 2017). Primary outcome was defined as resolution of CDI without recurrence in a two-month period. FMT was administered via colonoscopy, nasojejunal tube, or oral capsules. All stool donors were rigorously screened.

RESULTS: FMT was performed in 13 patients with R-CDI. Median age was 75.0 years and 76.9% were females. Six FMT were performed via nasojejunal tube, 5 via oral capsules, and 2 by colonoscopy. There were no procedure-related adverse events, except for bacteremia in one patient. During follow-up, R- CDI was observed in one patient at one month after FMT. The primary resolution rate was 83.3% and the overall resolution rate was 91.7%. FMT by capsules achieved a 100% resolution rate, colonoscopy 100%, and nasojejunal tube 80.0%.

CONCLUSIONS: In our cohort, FMT proved to be safe and effective, even in high risk patients. Oral administration in capsules also proved to be safe, well-tolerated, and highly effective for R-CDI. In our experience, the FMT capsule formulation seems feasible in the routine of a hospital. This administration method will allow FMT to be more widely used.

RevDate: 2018-11-05

Daniels LM, WD Kufel (2018)

Clinical review of Clostridium difficile infection: an update on treatment and prevention.

Expert opinion on pharmacotherapy, 19(16):1759-1769.

INTRODUCTION: Clostridium difficile infection (CDI) has become a significant healthcare-associated infection and is strongly associated with antibiotic use. Practice guidelines have recently been revised incorporating updated recommendations for diagnosis, treatment, and prevention. Areas covered: This review discusses updated aspects of CDI management. New and emerging pharmacologic options for treatment and prevention are reviewed. Expert opinion: Metronidazole is associated with lower rates of treatment success compared to vancomycin and should no longer be used as primary therapy for the first episode of CDI or recurrent disease. Vancomycin or fidaxomicin are now recommended for first-line therapy for most cases of CDI. Fecal microbiota transplant is effective and safe for the treatment of recurrent CDI. Evidence supports the use of fidaxomicin and bezlotoxumab for prevention of recurrent CDI; however, the costs associated with these therapies may limit their use. Validated risk prediction tools are needed to identify patients most likely to benefit from these treatments. Future advancements in microbiota targeting treatments will emerge as promising alternatives to standard CDI treatments. Antibiotic stewardship and infection control measures will remain essential components for CDI management.

RevDate: 2018-10-23

Schmulson M, M Bashashati (2018)

Fecal microbiota transfer for bowel disorders: efficacy or hype?.

Current opinion in pharmacology, 43:72-80 pii:S1471-4892(18)30074-2 [Epub ahead of print].

PURPOSE OF REVIEW: Dysbiosis has been related to the pathophysiology of disorders of - gut-brain interaction (DGBI) including irritable bowel syndrome (IBS) and functional constipation (FC). Accordingly, modulation of gut microbiota has been proposed as a potential treatment for these disorders. Gut microbiota modulation can be effected by probiotics, prebiotics, symbiotics, postbiotics, antibiotics and fecal transplantation (FMT) or bacteriotherapy. The latter is currently used for recurrent or severe Clostridium difficile colitis and has been the focus of recent research in IBS and FC.

RECENT FINDINGS: Several case series reported promising results for FMT in patients with IBS and FC, which prompted the conduction of randomized controlled trials (RCT) in these DGBI.

SUMMARY: Both case series and RCTs are herein discussed. To the best of our knowledge, as of yet, 5 RCTs have been published on IBS and one in FC with slow colonic transit. In IBS, the majority of studies have used the IBS severity scoring system (IBS-SSS) as an outcome measure; however, the selection criteria were different among the trials as well as the route and form of administration of the FMT. Therefore, the results are inconsistent and no conclusion can be drawn. Some studies suggest that the presence of post-infection (PI)-IBS and the baseline microbiota status in the donors could be predictor factors of successful FMT in IBS. In constipation with slow colonic transit, the FMT seems to be more effective, although the data is based on only one RCT. We believe that larger RCTs, controlled with true placebos and considering baseline intestinal microbiota of the study subjects as well as donors' microbiota are still needed before recommending FMT in IBS and/or FC. History of previous GI infection (e.g. PI-IBS) and IBS subtypes should also be taken into account.

RevDate: 2018-11-14

Diorio C, Robinson PD, Ammann RA, et al (2018)

Guideline for the Management of Clostridium Difficile Infection in Children and Adolescents With Cancer and Pediatric Hematopoietic Stem-Cell Transplantation Recipients.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology [Epub ahead of print].

Purpose The aim of this work was to develop a clinical practice guideline for the prevention and treatment of Clostridium difficile infection (CDI) in children and adolescents with cancer and pediatric hematopoietic stem-cell transplantation (HSCT) patients. Methods An international multidisciplinary panel of experts in pediatric oncology and infectious diseases with patient advocate representation was convened. We performed systematic reviews of randomized controlled trials for the prevention or treatment of CDI in any population and considered the directness of the evidence to children with cancer and pediatric HSCT patients. We used the Grading of Recommendations Assessment, Development, and Evaluation approach to generate recommendations. Results The panel made strong recommendations to administer either oral metronidazole or oral vancomycin for the initial treatment of nonsevere CDI and oral vancomycin for the initial treatment of severe CDI. Fidaxomicin may be considered in the setting of recurrent CDI. The panel suggested that probiotics not be routinely used for the prevention of CDI, and that monoclonal antibodies and probiotics not be routinely used for the treatment of CDI. A strong recommendation to not use fecal microbiota transplantation was made in this population. We identified key knowledge gaps and suggested directions for future research. Conclusion We present a guideline for the prevention and treatment of CDI in children and adolescents with cancer and pediatric HSCT patients. Future research should include randomized controlled trials that involve children with cancer and pediatric HSCT patients to improve the management of CDI in this population.

RevDate: 2018-11-14

Sunkara T, Rawla P, Ofosu A, et al (2018)

Fecal microbiota transplant - a new frontier in inflammatory bowel disease.

Journal of inflammation research, 11:321-328 pii:jir-11-321.

Inflammatory bowel disease (IBD) is a chronic multifactorial disease that affects the gastrointestinal tract and results from an aberrant immune response toward luminal antigens in genetically susceptible people. Most of the current therapies for IBD focus on the management of the inflammation by using corticosteroids, immune modulators, and more recently, monoclonal antibodies (biological therapy). Although these therapies provide benefit in most cases, there are still a significant number of patients who do not respond or become refractory over time, suggesting the need for alternative therapeutic options. In the last decade, it has been recognized that "dysbiosis," an imbalanced gut microbiota, is a key element in IBD suggesting microbiome-based therapies as an attractive approach. Recently, fecal microbiota transplant (FMT) has been successfully used for the treatment of Clostridium difficile infection, and it is now under investigation for the treatment of IBD. Clinical trials data are still poor but strongly support a future introduction of FMT in therapy to manage IBD microbiome. More studies are needed to assess the optimal route of administration and the frequency of FMT, the best matched donor for each patient as well as the risks associated with FMT in IBD.

RevDate: 2018-09-13

Ossorio PN, Y Zhou (2018)

Regulating stool for microbiota transplantation.

Gut microbes [Epub ahead of print].

In 2017 Gut Microbes published "A proposed definition of microbiota transplantation for regulatory purposes," in which the authors suggest that regulators should draw a line between microbiota transplants and biologic drugs composed of microbial communities (or other products derived from the human microbiome). They develop a definition of microbiota transplantation (MT) to help regulators draw such a line, and suggest that MT need not be, and cannot be, regulated as a biologic drug (a live biotherapeutic product). However, an agency's regulatory scrutiny of a medical product should be commensurate with that product's degree of risk to patients. Products for MT, such as stool, are likely to be as or more dangerous than more highly manipulated microbial products that scientists and regulators agree should be regulated as biologic drugs. Therefore, we argue that MT, as defined by the authors, should receive the same regulatory oversight as any other biologic product intended to cure, mitigate, treat, or prevent disease. We also suggest that regulators might not be able to operationalize the proposed definition of MT.

RevDate: 2018-11-14

Wang Z, Lou H, Wang Y, et al (2018)

GePMI: A statistical model for personal intestinal microbiome identification.

NPJ biofilms and microbiomes, 4:20 pii:65.

Human gut microbiomes consist of a large number of microbial genomes, which vary by diet and health conditions and from individual to individual. In the present work, we asked whether such variation or similarity could be measured and, if so, whether the results could be used for personal microbiome identification (PMI). To address this question, we herein propose a method to estimate the significance of similarity among human gut metagenomic samples based on reference-free, long k-mer features. Using these features, we find that pairwise similarities between the metagenomes of any two individuals obey a beta distribution and that a p value derived accordingly well characterizes whether two samples are from the same individual or not. We develop a computational framework called GePMI (Generating inter-individual similarity distribution for Personal Microbiome Identification) and apply it to several human gut metagenomic datasets (>300 individuals and >600 samples in total). From the results of GePMI, most of the human gut microbiomes can be identified (auROC = 0.9470, auPRC = 0.8702). Even after antibiotic treatment or fecal microbiota transplantation, the individual k-mer signature still maintains a certain specificity.

RevDate: 2018-11-30

Zuo T, Wong SH, Cheung CP, et al (2018)

Gut fungal dysbiosis correlates with reduced efficacy of fecal microbiota transplantation in Clostridium difficile infection.

Nature communications, 9(1):3663 pii:10.1038/s41467-018-06103-6.

Fecal microbiota transplantation (FMT) is effective in treating recurrent Clostridium difficile infection (CDI). Bacterial colonization in recipients after FMT has been studied, but little is known about the role of the gut fungal community, or mycobiota. Here, we show evidence of gut fungal dysbiosis in CDI, and that donor-derived fungal colonization in recipients is associated with FMT response. CDI is accompanied by over-representation of Candida albicans and decreased fungal diversity, richness, and evenness. Cure after FMT is associated with increased colonization of donor-derived fungal taxa in recipients. Recipients of successful FMT ("responders") display, after FMT, a high relative abundance of Saccharomyces and Aspergillus, whereas "nonresponders" and individuals treated with antibiotics display a dominant presence of Candida. High abundance of C. albicans in donor stool also correlates with reduced FMT efficacy. Furthermore, C. albicans reduces FMT efficacy in a mouse model of CDI, while antifungal treatment reestablishes its efficacy, supporting a potential causal relationship between gut fungal dysbiosis and FMT outcome.

RevDate: 2018-11-14

Wei YL, Chen YQ, Gong H, et al (2018)

Fecal Microbiota Transplantation Ameliorates Experimentally Induced Colitis in Mice by Upregulating AhR.

Frontiers in microbiology, 9:1921.

Ulcerative colitis (UC) is a chronic non-specific inflammatory disease that occurs in the colon and rectum. While fecal microbiota transplantation (FMT) is gaining attention as a clinical treatment of UC, the molecular mechanisms behind this effect have yet to be fully understood. A C57BL/6 mouse model was established to test whether FMT promotes the recovery of colon inflammation. Administration of 2% dextran sulfate sodium (DSS) for 7 days successfully induced acute colitis, as evidenced by diarrhea, hematochezia and colon shortening as well as a decrease in body weight. FMT alleviated the severity of colon mucosa injury and improved histological alterations compared with that of the DSS group. In addition, FMT promoted homeostasis of the intestinal microbiota. Furthermore, FMT upregulated the expression of aryl hydrocarbon receptor (AHR), interleukin-10 (IL-10), and transforming growth factor beta (TGF-β) in colon tissues. These results suggest that the significant anti-inflammatory effect of FMT may be attributed to its promotion of IL-10 and TGF-β production and AHR activation. Based on these results, FMT had a favorable therapeutic effect on DSS-induced colitis.

RevDate: 2018-11-14

Luo Y, Zeng B, Zeng L, et al (2018)

Gut microbiota regulates mouse behaviors through glucocorticoid receptor pathway genes in the hippocampus.

Translational psychiatry, 8(1):187 pii:10.1038/s41398-018-0240-5.

Gut microbiota has an important role in the immune system, metabolism, and digestion, and has a significant effect on the nervous system. Recent studies have revealed that abnormal gut microbiota induces abnormal behaviors, which may be associated with the hypothalamic-pituitary-adrenal (HPA) axis. Therefore, we investigated the behavioral changes in germ-free (GF) mice by behavioral tests, quantified the basal serum cortisol levels, and examined glucocorticoid receptor pathway genes in hippocampus using microarray analysis followed by real-time PCR validation, to explore the molecular mechanisms by which the gut microbiota influences the host's behaviors and brain function. Moreover, we quantified the basal serum cortisol levels and validated the differential genes in an Escherichia coli-derived lipopolysaccharide (LPS) treatment mouse model and fecal "depression microbiota" transplantation mouse model by real-time PCR. We found that GF mice showed antianxiety- and antidepressant-like behaviors, whereas E. coli LPS-treated mice showed antidepressant-like behavior, but did not show antianxiety-like behavior. However, "depression microbiota" recipient mice exhibited anxiety- and depressive-like behaviors. In addition, six glucocorticoid receptor pathway genes (Slc22a5, Aqp1, Stat5a, Ampd3, Plekhf1, and Cyb561) were upregulated in GF mice, and of these only two (Stat5a and Ampd3) were upregulated in LPS-treated mice, whereas the shared gene, Stat5a, was downregulated in "depression microbiota" recipient mice. Furthermore, basal serum cortisol levels were decreased in E. coli LPS-treated mice but not in GF mice and "depression microbiota" recipient mice. These results indicated that the gut microbiota may lead to behavioral abnormalities in mice through the downstream pathway of the glucocorticoid receptor. Herein, we proposed a new insight into the molecular mechanisms by which gut microbiota influence depressive-like behavior.

RevDate: 2018-09-05

Monaghan T, Mullish BH, Patterson J, et al (2018)

Effective fecal microbiota transplantation for recurrent Clostridioides difficile infection in humans is associated with increased signalling in the bile acid-farnesoid X receptor-fibroblast growth factor pathway.

Gut microbes [Epub ahead of print].

The mechanisms of efficacy for fecal microbiota transplantation (FMT) in treating recurrent Clostridioides difficile infection (rCDI) remain poorly defined, with restored gut microbiota-bile acid interactions representing one possible explanation. Furthermore, the potential implications for host physiology of these FMT-related changes in gut bile acid metabolism are also not well explored. In this study, we investigated the impact of FMT for rCDI upon signalling through the farnesoid X receptor (FXR)-fibroblast growth factor (FGF) pathway. Herein, we identify that in addition to restoration of gut microbiota and bile acid profiles, FMT for rCDI is accompanied by a significant, sustained increase in circulating levels of FGF19 and reduction in FGF21. These FGF changes were associated with weight gain post-FMT, to a level not exceeding the pre-rCDI baseline. Collectively, these data support the hypothesis that the restoration of gut microbial communities by FMT for rCDI is associated with an upregulated FXR-FGF pathway, and highlight the potential systemic effect of FMT.

RevDate: 2018-09-29

Wang JW, Kuo CH, Kuo FC, et al (2018)

Fecal microbiota transplantation: Review and update.

Journal of the Formosan Medical Association = Taiwan yi zhi pii:S0929-6646(18)30555-2 [Epub ahead of print].

Fecal microbiota transplantation (FMT) is a method to directly change the recipient's gut microbiota to normalize the composition and gain a therapeutic benefit. The history of FMT has been traced back to the 4th century and has been highly regarded since 2013, when the United States Food and Drug Administration approved FMT for treating recurrent and refractory Clostridium difficile infection. Since then, the range of FMT applications extended rapidly and broadly not only in gastrointestinal disorders, but also in extra-gastrointestinal diseases. Donor selection with questionnaire, interview, blood tests, and stool examinations should be strictly performed before FMT to reduce and prevent occurrence of any adverse events. Step-by-step cautious fecal and recipient preparation along with adequately choosing delivery methods based on individual clinical situations are key points of the FMT process. Although current evidence deems FMT as a generally safe therapeutic method with few adverse effects, the long-term outcomes of FMT have not been completely elucidated. Therefore, establishing periodicity and length of regular follow-up after FMT to monitor the clinical efficacy and long-term adverse events are other essential issues. In the future, we will look forward to personalized FMT for different patients and conditions according to varied hosts and diseases.

RevDate: 2018-09-04

Han R, Ma J, H Li (2018)

Mechanistic and therapeutic advances in non-alcoholic fatty liver disease by targeting the gut microbiota.

Frontiers of medicine pii:10.1007/s11684-018-0645-9 [Epub ahead of print].

Non-alcoholic fatty liver disease (NAFLD) is one of the most common metabolic diseases currently in the context of obesity worldwide, which contains a spectrum of chronic liver diseases, including hepatic steatosis, non-alcoholic steatohepatitis and hepatic carcinoma. In addition to the classical "Two-hit" theory, NAFLD has been recognized as a typical gut microbiota-related disease because of the intricate role of gut microbiota in maintaining human health and disease formation. Moreover, gut microbiota is even regarded as a "metabolic organ" that play complementary roles to that of liver in many aspects. The mechanisms underlying gut microbiota-mediated development of NAFLD include modulation of host energy metabolism, insulin sensitivity, and bile acid and choline metabolism. As a result, gut microbiota have been emerging as a novel therapeutic target for NAFLD by manipulating it in various ways, including probiotics, prebiotics, synbiotics, antibiotics, fecal microbiota transplantation, and herbal components. In this review, we summarized the most recent advances in gut microbiota-mediated mechanisms, as well as gut microbiota-targeted therapies on NAFLD.

RevDate: 2018-09-26
CmpDate: 2018-09-26

Gupta A, Cifu AS, S Khanna (2018)

Diagnosis and Treatment of Clostridium difficile Infection.

JAMA, 320(10):1031-1032.

RevDate: 2018-10-10

Ruiz L, López P, Suárez A, et al (2018)

The role of gut microbiota in lupus: what we know in 2018?.

Expert review of clinical immunology, 14(10):787-792.

INTRODUCTION: The role of the human intestinal microbiota in the maintenance of a healthy physiological condition, as well as its relation to the development of disease, remains to be clarified. Current evidence suggests that intestinal microbes could be involved in the initiation and amplification of autoimmune diseases, including rheumatoid arthritis and systemic lupus erythematosus (SLE). Despite recent progress in understanding how these microbes influence the pathophysiology of lupus, studies are still limited. Areas covered: In this review, we have tried to summarize the most relevant findings that have contributed to our understanding of the links between the human intestinal microbiota and the development of lupus. We also describe the potential role of individual microbial players in the physiology of lupus, and how they can shape relevant immune responses. Expert commentary: Culture-independent techniques based on massive sequencing represent a powerful tool to unravel the biological activity of gut microbes. Current data demonstrates that, depending on the pattern of intestinal microorganisms or the presence of specific bacteria, different responses related to lupus physiology can be triggered. Fecal microbiota transplantation, live biotherapeutics, or dietary interventions targeting the microbiota will likely become a treatment for SLE.

RevDate: 2018-09-27

Delaune V, Orci LA, Lacotte S, et al (2018)

Fecal microbiota transplantation: a promising strategy in preventing the progression of non-alcoholic steatohepatitis and improving the anti-cancer immune response.

Expert opinion on biological therapy, 18(10):1061-1071.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) has the potential to progress to hepatocellular carcinoma (HCC). However, limited therapies are currently available for the treatment of advanced HCC, and one must strive to search for novel strategies. Areas covered: We provide insight on current knowledge related to gut microbiota and NAFLD, summarize the sequence linking obesity to HCC and highlight gut dysbiosis in obesity and its consequences on the liver. We detail the impact of the gut microbiota on immune checkpoint inhibitors, and speculate on the role of fecal microbiota transplantation (FMT) in NAFLD and in improving anti-neoplastic immune response. Expert Opinion: Manipulation of the gut microbiota seems promising in the secondary prevention of NAFLD/NASH and/or in potentiating anti-cancer immune response, notably by a global 'resetting' using FMT. However, the composition of a 'harmful' gut microbiome in HCC still needs to be characterized, and the impact of FMT on HCC growth needs to be assessed.

RevDate: 2018-11-26
CmpDate: 2018-11-26

Hum RM, Deambrosis D, Lum SH, et al (2018)

Molecular monitoring of adenovirus reactivation in faeces after haematopoietic stem-cell transplantation to predict systemic infection: a retrospective cohort study.

The Lancet. Haematology, 5(9):e422-e429.

BACKGROUND: Faecal shedding of adenovirus following allogeneic haematopoietic stem-cell transplantation (HSCT) is an early sign of loss of immune control over adenovirus, but there is no consensus on the role of monitoring of faecal adenoviral load by serial testing. We investigated whether serial faecal PCR monitoring could predict the risk of adenoviraemia and survival outcomes after HSCT.

METHODS: We did a retrospective cohort study at the Royal Manchester Children's Hospital, Manchester, UK, of patients who had received their first allogeneic HSCT between Feb 1, 2003, and Sept 1, 2016, and adenovirus infection recorded in their medical records. We excluded patients who had received second or third transplants or autologous HSCT transplants. We obtained characteristics of patients and transplants, including mortality and adenoviral reactivation, from medical records and the hospital database. All patients had blood samples tested weekly for adenovirus by PCR until immunosuppression was stopped and CD3 T-cell count recovered to greater than 0·3 × 109/L. Faecal PCR was done before transplantation in all patients, and after transplantation in patients who had diarrhoea, at the onset of symptoms and weekly thereafter until diarrhoea resolved. We analysed all samples available before and after HSCT. We did subgroup analyses for patients undergoing HSCT for cancer versus non-malignant conditions. We also assessed whether 5 log10 copies per g faeces was a suitable predictive threshold for adenoviraemia.

FINDINGS: We included 341 patients who had undergone a first allogeneic HSCT (median age 4·6 years, IQR 1·5-8·0, range 0-20·0). After HSCT, PCR was done in 4116 faecal samples from 293 (86%) patients who had diarrhoea and in 10 649 blood samples from 341 patients. Follow-up ended on July 14, 2017. 173 (59%) of 293 patients had adenovirus in faecal samples and 63 (18%) of 341 had adenovirus in blood samples. Maximum faecal viral load before adenoviraemia correlated significantly with maximum blood viral load (r=0·51, 95% CI 0·38-0·61, p<0·0001). Faecal adenoviral viral load greater than 5 log10 copies per g faeces was predictive of adenoviraemia (odds ratio 10·2, 95% CI 4·9-21·6, p<0·0001) with sensitivity 75·9% and specificity 74·8%. These values were increased further in patients with cancer, to 86·4% and 87·5%, respectively. Among the 28 patients who had positive faecal and blood samples and who had undergone serial faecal PCR monitoring after HSCT, the median time between reaching the faecal viral load threshold and onset of adenoviraemia was 8·0 days (IQR 2·3-21·8, 95% CI 4·0-16·0). Non-relapse mortality was not associated with adenovirus reactivation in faeces alone (9·2%, 95% CI 5·4-14·3 in patients without reactivation vs 7·8%, 3·8-13·7 in those with positive faeces only), but was significantly increased in patients who developed adenoviraemia (27·0%, 95% CI 16·7-38·4, p<0·0001).

INTERPRETATION: We identified a threshold faecal viral load that can predict the risk of adenoviraemia. Our findings support proliferation of adenovirus in the gastrointestinal tract before viraemia develops. Faecal PCR is suitable for early detection of children and young adults at risk of adenoviraemia, and its use might help reduce non-relapse mortality in allogeneic HSCT recipients.

FUNDING: None.

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ESP Quick Facts

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In the early 1990's, Robert Robbins was a faculty member at Johns Hopkins, where he directed the informatics core of GDB — the human gene-mapping database of the international human genome project. To share papers with colleagues around the world, he set up a small paper-sharing section on his personal web page. This small project evolved into The Electronic Scholarly Publishing Project.

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In 1995, Robbins became the VP/IT of the Fred Hutchinson Cancer Research Center in Seattle, WA. Soon after arriving in Seattle, Robbins secured funding, through the ELSI component of the US Human Genome Project, to create the original ESP.ORG web site, with the formal goal of providing free, world-wide access to the literature of classical genetics.

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Although the methods of molecular biology can seem almost magical to the uninitiated, the original techniques of classical genetics are readily appreciated by one and all: cross individuals that differ in some inherited trait, collect all of the progeny, score their attributes, and propose mechanisms to explain the patterns of inheritance observed.

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Usage of the site grew rapidly and has remained high. Faculty began to use the site for their assigned readings. Other on-line publishers, ranging from The New York Times to Nature referenced ESP materials in their own publications. Nobel laureates (e.g., Joshua Lederberg) regularly used the site and even wrote to suggest changes and improvements.

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When the site began, no journals were making their early content available in digital format. As a result, ESP was obliged to digitize classic literature before it could be made available. For many important papers — such as Mendel's original paper or the first genetic map — ESP had to produce entirely new typeset versions of the works, if they were to be available in a high-quality format.

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Early support from the DOE component of the Human Genome Project was critically important for getting the ESP project on a firm foundation. Since that funding ended (nearly 20 years ago), the project has been operated as a purely volunteer effort. Anyone wishing to assist in these efforts should send an email to Robbins.

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With the development of methods for adding typeset side notes to PDF files, the ESP project now plans to add annotated versions of some classical papers to its holdings. We also plan to add new reference and pedagogical material. We have already started providing regularly updated, comprehensive bibliographies to the ESP.ORG site.

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Papers in Classical Genetics

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Along with papers on classical genetics, ESP offers a collection of full-text digital books, including many works by Darwin (and even a collection of poetry — Chicago Poems by Carl Sandburg).

Timelines

ESP now offers a much improved and expanded collection of timelines, designed to give the user choice over subject matter and dates.

Biographies

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Selected Bibliographies

Bibliographies on several topics of potential interest to the ESP community are now being automatically maintained and generated on the ESP site.

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