scholarly journals Re-evaluating the evidence for fecal microbiota transplantation “super-donors” in inflammatory bowel disease

2019 ◽  
Author(s):  
Scott W. Olesen ◽  
Ylaine Gerardin
Keyword(s):  
Inflammatory Bowel Disease ◽  
Clinical Trials ◽  
Bowel Disease ◽  
Large Scale ◽  
Fecal Microbiota Transplantation ◽  
Meta Analysis ◽  
Fecal Microbiota ◽  
Recommended Treatment ◽  
Clostridioides Difficile ◽  
Inflammatory Bowel

ABSTRACTFecal microbiota transplantation (FMT) is a recommended treatment for recurrent Clostridioides difficile infection, and there is promise that FMT may be effective for conditions like inflammatory bowel disease (IBD). Previous FMT clinical trials have considered the possibility of a “donor effect”, that is, that FMT material from different donors has different clinical efficacies. Here we lay out rigorous statistical methodology for detecting donor effects, finding that reliable detection of a donor effect requires trials with more than 200 FMT-treated patients. A re-evaluation of previous FMT clinical trials for IBD showed that while there is very little evidence for a non-zero donor effect, the existing data are also not inconsistent with substantial donor effects. Large-scale meta-analysis, combined with careful reporting from clinical trials, will be crucial in determining if donor effects are clinically relevant for IBD.

Efficacy of Fecal Microbiota Transplantation for Recurrent C. Difficile Infection in Inflammatory Bowel Disease

2019 ◽  
Vol 26 (9) ◽  
pp. 1415-1420 ◽  
Author(s):  
Raseen Tariq ◽  
Molly B Disbrow ◽  
John K Dibaise ◽  
Robert Orenstein ◽  
Srishti Saha ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Fecal Microbiota Transplantation ◽  
Median Number ◽  
Fecal Microbiota ◽  
Indeterminate Colitis ◽  
Clinical Predictors ◽  
Fecal Microbiota Transplant ◽  
Clostridioides Difficile ◽  
Inflammatory Bowel

Abstract Background Clostridioides difficile infection (CDI) is associated with poor outcomes in inflammatory bowel disease (IBD) patients. Data are scarce on efficacy of fecal microbiota transplant (FMT) for recurrent CDI in IBD patients. Methods We reviewed health records of IBD patients (18 years of age or older) with recurrent CDI who underwent FMT. Outcomes of FMT for CDI were assessed on the basis of symptoms and stool test results. Results We included 145 patients (75 women [51.7%]; median age, 46 years). Median IBD duration was 8 (range, 0–47) years, 36.6% had Crohn disease, 61.4% had ulcerative colitis, and 2.1% had indeterminate colitis. Median number of prior CDI episodes was 3 (range, 3–20), and 61.4% had received vancomycin taper. Diarrhea resolved after FMT in 48 patients (33.1%) without further testing. Ninety-five patients (65.5%) underwent CDI testing owing to post-FMT recurrent diarrhea; 29 (20.0%) had positive results. After FMT, 2 patients received empiric treatment of recurrent CDI without symptom resolution, suggesting IBD was the cause of symptoms. The overall cure rate of CDI after FMT was 80.0%, without CDI recurrence at median follow-up of 9.3 (range, 0.1–51) months. Forty-three patients (29.7%) had planned IBD therapy escalation after CDI resolution; none de-escalated or discontinued IBD therapy. Overall, 7.6% had worsening IBD symptoms after FMT that were treated as new IBD flares. No clinical predictors of FMT failure were identified. Conclusions Few patients had new IBD flare after FMT. Fecal microbiota transplantation effectively treats recurrent CDI in IBD patients but has no apparent beneficial effect on the IBD course.

scholarly journals Fecal Microbiota Transplantation: Screening and Selection to Choose the Optimal Donor

2020 ◽  
Vol 9 (6) ◽  
pp. 1757 ◽  
Author(s):  
Stefano Bibbò ◽  
Carlo Romano Settanni ◽  
Serena Porcari ◽  
Enrico Bocchino ◽  
Gianluca Ianiro ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Metabolic Disorders ◽  
Fecal Microbiota Transplantation ◽  
Functional Gastrointestinal Disorders ◽  
Fecal Microbiota ◽  
Effective Treatment Option ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
Inflammatory Bowel

In the past decade, fecal microbiota transplantation (FMT) has rapidly spread worldwide in clinical practice as a highly effective treatment option against recurrent Clostridioides difficile infection. Moreover, new evidence also supports a role for FMT in other conditions, such as inflammatory bowel disease, functional gastrointestinal disorders, or metabolic disorders. Recently, some studies have identified specific microbial characteristics associated with clinical improvement after FMT, in different disorders, paving the way for a microbiota-based precision medicine approach. Moreover, donor screening has become increasingly more complex over years, along with standardization of FMT and the increasing number of stool banks. In this narrative review, we discuss most recent evidence on the screening and selection of the stool donor, with reference to recent studies that have identified specific microbiological features for clinical conditions such as Clostridioides difficile infection, irritable bowel syndrome, inflammatory bowel disease, and metabolic disorders.

scholarly journals The risk of inflammatory bowel disease flares after fecal microbiota transplantation: Systematic review and meta-analysis

Gut Microbes ◽  
2017 ◽  
Vol 8 (6) ◽  
pp. 574-588 ◽  
Author(s):  
Taha Qazi ◽  
Thelina Amaratunga ◽  
Edward L. Barnes ◽  
Monika Fischer ◽  
Zain Kassam ◽  
...  
Keyword(s):  
Systematic Review ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Fecal Microbiota Transplantation ◽  
Meta Analysis ◽  
Fecal Microbiota ◽  
Inflammatory Bowel

scholarly journals Designing fecal microbiota transplant trials that account for differences in donor stool efficacy

2017 ◽  
Vol 27 (10) ◽  
pp. 2906-2917 ◽  
Author(s):  
Scott W Olesen ◽  
Thomas Gurry ◽  
Eric J Alm
Keyword(s):  
Inflammatory Bowel Disease ◽  
Clinical Trials ◽  
Bowel Disease ◽  
Statistical Power ◽  
Fecal Microbiota Transplantation ◽  
Optimal Strategies ◽  
Fecal Microbiota ◽  
Fecal Microbiota Transplant ◽  
Number Of Patients ◽  
Inflammatory Bowel

Fecal microbiota transplantation is a highly effective intervention for patients suffering from recurrent Clostridium difficile, a common hospital-acquired infection. Fecal microbiota transplantation’s success as a therapy for C. difficile has inspired interest in performing clinical trials that experiment with fecal microbiota transplantation as a therapy for other conditions like inflammatory bowel disease, obesity, diabetes, and Parkinson’s disease. Results from clinical trials that use fecal microbiota transplantation to treat inflammatory bowel disease suggest that, for at least one condition beyond C. difficile, most fecal microbiota transplantation donors produce stool that is not efficacious. The optimal strategies for identifying and using efficacious donors have not been investigated. We therefore examined the optimal Bayesian response-adaptive strategy for allocating patients to donors and formulated a computationally tractable myopic heuristic. This heuristic computes the probability that a donor is efficacious by updating prior expectations about the efficacy of fecal microbiota transplantation, the placebo rate, and the fraction of donors that produce efficacious stool. In simulations designed to mimic a recent fecal microbiota transplantation clinical trial, for which traditional power calculations predict [Formula: see text] statistical power, we found that accounting for differences in donor stool efficacy reduced the predicted statistical power to [Formula: see text]. For these simulations, using the heuristic Bayesian allocation strategy more than quadrupled the statistical power to [Formula: see text]. We use the results of similar simulations to make recommendations about the number of patients, the number of donors, and the choice of clinical endpoint that clinical trials should use to optimize their ability to detect if fecal microbiota transplantation is effective for treating a condition.

scholarly journals Designing fecal microbiota transplant trials that account for differences in donor stool efficacy

2016 ◽  
Author(s):  
Scott W. Olesen ◽  
Thomas Gurry ◽  
Eric J. Alm
Keyword(s):  
Inflammatory Bowel Disease ◽  
Clinical Trials ◽  
Bowel Disease ◽  
Statistical Power ◽  
Fecal Microbiota Transplantation ◽  
Optimal Strategies ◽  
Fecal Microbiota ◽  
Fecal Microbiota Transplant ◽  
Number Of Patients ◽  
Inflammatory Bowel

1AbstractFecal microbiota transplantation (FMT) is a highly effective intervention for patients suffering from recurrent Clostridium difficile, a common hospital-acquired infection. FMT’s success as a therapy for C. difficile has inspired interest in performing clinical trials that experiment with FMT as a therapy for other conditions like inflammatory bowel disease, obesity, diabetes, and Parkinson’s disease. Results from clinical trials that use FMT to treat inflammatory bowel disease suggest that, for at least one condition beyond C. difficile, most FMT donors produce stool that is not efficacious. The optimal strategies for identifying and using efficacious donors have not been investigated. We therefore examined the optimal Bayesian response-adaptive strategy for allocating patients to donors and formulated a computationally-tractable myopic heuristic. This heuristic computes the probability that a donor is efficacious by updating prior expectations about the efficacy of FMT, the placebo rate, and the fraction of donors that produce efficacious stool. In simulations designed to mimic a recent FMT clinical trial, for which traditional power calculations predict ~100% statistical power, we found that accounting for differences in donor stool efficacy reduced the predicted statistical power to ~9%. For these simulations, using the heuristic Bayesian allocation strategy more than quadrupled the statistical power to ~39%. We use the results of similar simulations to make recommendations about the number of patients, number of donors, and choice of clinical endpoint that clinical trials should use to optimize their ability to detect if FMT is effective for treating a condition.

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