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Bacteriophage transfer during faecal microbiota transplantation in Clostridium difficile infection is associated with treatment outcome.

ABSTRACT: OBJECTIVE:Faecal microbiota transplantation (FMT) is effective for the treatment of recurrent Clostridium difficile infection (CDI). Studies have shown bacterial colonisation after FMT, but data on viral alterations in CDI are scarce. We investigated enteric virome alterations in CDI and the association between viral transfer and clinical outcome in patients with CDI. DESIGN:Ultra-deep metagenomic sequencing of virus-like particle preparations and bacterial 16S rRNA sequencing were performed on stool samples from 24 subjects with CDI and 20 healthy controls. We longitudinally assessed the virome and bacterial microbiome changes in nine CDI subjects treated with FMT and five treated with vancomycin. Enteric virome alterations were assessed in association with treatment response. RESULTS:Subjects with CDI demonstrated a significantly higher abundance of bacteriophage Caudovirales and a lower Caudovirales diversity, richness and evenness compared with healthy household controls. Significant correlations were observed between bacterial families Proteobacteria, Actinobacteria and Caudovirales taxa in CDI. FMT treatment resulted in a significant decrease in the abundance of Caudovirales in CDI. Cure after FMT was observed when donor-derived Caudovirales contigs occupied a larger fraction of the enteric virome in the recipients (p=0.024). In treatment responders, FMT was associated with alterations in the virome and the bacterial microbiome, while vancomycin treatment led to alterations in the bacterial community alone. CONCLUSIONS:In a preliminary study, CDI is characterised by enteric virome dysbiosis. Treatment response in FMT was associated with a high colonisation level of donor-derived Caudovirales taxa in the recipient. Caudovirales bacteriophages may play a role in the efficacy of FMT in CDI. TRIAL REGISTRATION NUMBER:NCT02570477.

SUBMITTER: Zuo T

PROVIDER: S-EPMC5868238 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Bacteriophage transfer during faecal microbiota transplantation in <i>Clostridium difficile</i> infection is associated with treatment outcome.

Zuo Tao T Wong Sunny H SH Lam Kelvin K Lui Rashid R Cheung Kitty K Tang Whitney W Ching Jessica Y L JYL Chan Paul K S PKS Chan Martin C W MCW Wu Justin C Y JCY Chan Francis K L FKL Yu Jun J Sung Joseph J Y JJY Ng Siew C SC

Gut 20170524 4

<h4>Objective</h4>Faecal microbiota transplantation (FMT) is effective for the treatment of recurrent <i>Clostridium difficile</i> infection (CDI). Studies have shown bacterial colonisation after FMT, but data on viral alterations in CDI are scarce. We investigated enteric virome alterations in CDI and the association between viral transfer and clinical outcome in patients with CDI.<h4>Design</h4>Ultra-deep metagenomic sequencing of virus-like particle preparations and bacterial 16S rRNA sequenc ...[more]

PMID: 28539351

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Project description:A significant fraction of patients with recurrent Clostridium difficile infections (CDI) have inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) can break the cycle of CDI recurrence and can be performed without evaluation of the colon. We evaluated the efficacy of colonoscopic FMT in patients with and without IBD, and whether we could identify IBD in patients during this procedure.We collected clinical meta-data and colonoscopy results from 272 consecutive patients that underwent FMT for recurrent CDI at the University of Minnesota from 2008 through 2015. Patients had at least 2 spontaneous relapses of CDI following their initial episode and did not clear the infection after 1 extended antibiotic regimen. We collected random mucosal biopsies from patients' right colons to identify lymphocytic or collagenous colitis during the FMT procedure. Failure or success in clearing CDI was determined within or at 2 months after the FMT.Of patients undergoing FMT, 15% had established IBD and 2.6% were found to have IBD during the FMT procedure. A single colonoscopic FMT cleared CDI from 74.4% of patients with IBD and 92.1% of patients without IBD (P = .0018). Patients had similar responses to FMT regardless of immunosuppressive therapy. More than one-quarter of patients with IBD (25.6%) had a clinically significant flare of IBD after FMT. Lymphocytic colitis was documented in 7.4% of patients with endoscopically normal colon mucosa; only 3 of these patients (20%) required additional treatment for colitis after clearance of CDI.Based on an analysis of 272 patients, FMT is somewhat less effective in clearing recurrent CDI from patients with IBD, compared with patients without IBD, regardless of immunosuppressive therapy. More than 25% of patients with IBD have a disease flare following FMT. Lymphocytic colitis did not affect the outcome of FMT, but a small fraction of these patients required pharmacologic treatment after the procedure.

Project description:BackgroundClostridioides difficile infection (CDI) and inflammatory bowel disease (IBD) are global gastroenterological diseases that cause considerable burden on human health, healthcare systems, and society. Faecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides Difficile Infection (rCDI) and a promising therapy for IBD. However, indication for FMT in IBD is still unofficial. Consequently, the National Institute for Health and Care Excellence (NICE) is seeking healthcare providers' advice on whether to update FMT guidelines.MethodsA systematic review methodology was adopted for this study. Five databases (CINAHL, MEDLINE, Cochrane Library, Scopus, Web of Science) and grey literature were systematically searched for English language literature to 14 May 2021. The quality of the included studies was then appraised using the Institute for Public Health Sciences cross-sectional studies tool, after which the findings of the studies were narratively synthesised.ResultsThirteen cross-sectional studies with 4110 validated questionnaire responses were included. Narrative synthesis found that 39.43% of respondents were familiar with FMT (N = 3746, 95%CI = 37.87%-41%), 58.81% of respondents would recommend FMT to their patients (N = 1141, 95%CI = 55.95%-61.67%), 66.67% of respondents considered lack of clinical evidence was the greatest concern regarding FMT (N = 1941, 95%CI = 64.57%-68.77%), and 40.43% respondents would not implement FMT due to concerns about infection transmission (N = 1128, 95%CI = 37.57%-43.29%).ConclusionHealthcare providers' knowledge of FMT is relatively low and education is an effective strategy to improve it. As knowledge of FMT increases, willingness to recommend it also increases. Strengthening FMT clinical efficacy and reducing infection can enhance its public acceptance, application and popularity. However, further research is required to explore the donor screening procedure.

Project description: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.

Project description:Faecal microbiota transplantation (FMT) is the transfer of screened and minimally processed faecal material from a 'healthy' donor to 'diseased' recipient. It has an established role, and is recommended as a therapeutic strategy, in the management of recurrent Clostridioides difficile infection (CDI). Recognition that gut dysbiosis is associated with, and may contribute to, numerous disease states has led to interest in exploiting FMT to 'correct' this microbial imbalance. Conditions for which it is proposed to be beneficial include inflammatory bowel disease, irritable bowel syndrome, liver disease and hepatic encephalopathy, neuropsychiatric conditions such as depression and anxiety, systemic inflammatory states like sepsis, and even coronavirus disease 2019. To understand what role, if any, FMT may play in the management of these conditions, it is important to consider the potential risks and benefits of the therapy. Regardless, there are several barriers to its more widespread adoption, which include incompletely understood mechanism of action (especially outside of CDI), inability to standardise treatment, disagreement on its active ingredients and how it should be regulated, and lack of long-term outcome and safety data. Whilst the transfer of faecal material from one individual to another to treat ailments or improve health has a history dating back thousands of years, there are fewer than 10 randomised controlled trials supporting its use. Moving forward, it will be imperative to gather as much data from FMT donors and recipients over as long a timeframe as possible, and for trials to be conducted with rigorous methodology, including appropriate control groups, in order to best understand the utility of FMT for indications beyond CDI. This review discusses the history of FMT, its appreciable mechanisms of action with reference to CDI, indications for FMT with an emerging evidence base above and beyond CDI, and future perspectives on the field.

Dataset Information

Bacteriophage transfer during faecal microbiota transplantation in Clostridium difficile infection is associated with treatment outcome.

Publications

Bacteriophage transfer during faecal microbiota transplantation in <i>Clostridium difficile</i> infection is associated with treatment outcome.

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