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 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.

scholarly journals Gleaning Insights from Fecal Microbiota Transplantation and Probiotic Studies for the Rational Design of Combination Microbial Therapies

2016 ◽  
Vol 30 (1) ◽  
pp. 191-231 ◽  
Author(s):  
Lauren E. Hudson ◽  
Sarah E. Anderson ◽  
Anita H. Corbett ◽  
Tracey J. Lamb
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Rational Design ◽  
Fecal Microbiota Transplantation ◽  
Gastrointestinal Diseases ◽  
Fecal Microbiota ◽  
Inflammatory Disorder ◽  
Fecal Microbiota Transplant ◽  
Content Type ◽  
Inflammatory Bowel

SUMMARY Beneficial microorganisms hold promise for the treatment of numerous gastrointestinal diseases. The transfer of whole microbiota via fecal transplantation has already been shown to ameliorate the severity of diseases such as Clostridium difficile infection, inflammatory bowel disease, and others. However, the exact mechanisms of fecal microbiota transplant efficacy and the particular strains conferring this benefit are still unclear. Rationally designed combinations of microbial preparations may enable more efficient and effective treatment approaches tailored to particular diseases. Here we use an infectious disease, C. difficile infection, and an inflammatory disorder, the inflammatory bowel disease ulcerative colitis, as examples to facilitate the discussion of how microbial therapy might be rationally designed for specific gastrointestinal diseases. Fecal microbiota transplantation has already shown some efficacy in the treatment of both these disorders; detailed comparisons of studies evaluating commensal and probiotic organisms in the context of these disparate gastrointestinal diseases may shed light on potential protective mechanisms and elucidate how future microbial therapies can be tailored to particular diseases.

scholarly journals Characteristics of Fecal Microbiota Transplantation Use in Inflammatory Bowel Disease Cohort

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Christina M Bauer ◽  
Xian Zhang ◽  
Millie D Long ◽  
Robert S Sandler
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Medical Professional ◽  
Indeterminate Colitis ◽  
Routes Of Administration ◽  
Patient Reported ◽  
Inflammatory Bowel

Abstract Background There is a growing interest in the role of gut bacteria in a number of diseases and an emerging hypothesis that inflammatory bowel disease (IBD) is triggered by microbial dysbiosis in genetically susceptible individuals. Currently, fecal microbiota transplantation (FMT) is utilized for the treatment of Clostridium difficile colitis. Data on the efficacy of FMT for IBD are mixed, but patients are interested in its use for the treatment of IBD. We sought to describe the use of FMT (self or medical professional administered) in individuals with IBD using IBD Partners, an Internet-based cohort. Methods Patients enrolled in the IBD Partners cohort were offered the opportunity to complete an optional survey on the use of FMT between January 2017 to September 2018 (n = 5430). A cross-sectional analysis was performed within patients who completed the survey and did not have a pouch or ostomy. Patients’ demographic characteristics, disease activity and phenotype, mode of FMT delivery, and patient-reported efficacy were compared. Results Among 3274 eligible patients, 51 (1.6%) responded that they had an FMT in the past. Of patients undergoing FMT, 22 patients had the FMT for C. difficile while 29 reported that the FMT was for another indication. Most patients receiving FMT for an indication other than C. difficile had ulcerative colitis/indeterminate colitis (25, 86.2%). Colonoscopy (68.2%) and nasogastric tube (18.2%) were the most common routes of administration for patients receiving FMT for C. difficile colitis. Self-administration (72.4%) and enemas (17.2%) were the most common routes of administration in patients receiving FMT for an alternate indication. Patients reporting FMT for an indication other than C. difficile were less likely to have a physician directing their FMT treatment (20.6%) as compared to patients receiving FMT for C. difficile (86.3%). Patient-reported efficacy was lower for FMT given for a non-C. difficile indication. Conclusions Patients undergoing FMT for an indication other than C. difficile infection were more likely to have ulcerative colitis, self-administer FMT, and were less likely to be receiving FMT under the guidance of a medical professional. FMT was not as effective for symptoms when given for a non-C. difficile indication. Patients should be counseled on potential harms and lack of proven benefit associated with FMT for IBD indications to try to discourage self-administered FMT without proper medical oversite.

scholarly journals A163 MAJORITY OF INFLAMMATORY BOWEL DISEASE PATIENTS WITH RECURRENT CLOSTRIDIOIDES INFECTION DO NOT REQUIRE FECAL MICROBIOTA TRANSPLANTATION

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 171-173
Author(s):  
B Balram ◽  
n winczura ◽  
D H Kao ◽  
L A Dieleman ◽  
B Halloran ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Clinical Symptoms ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Clostridioides Difficile ◽  
Increased Risk ◽  
Severity Scores ◽  
Inflammatory Bowel ◽  
Treatment Escalation

Abstract Background Patients with inflammatory bowel disease (IBD) are at increased risk of developing Clostridioides difficile infection (CDI) and have worse outcomes including higher rates of colectomy and death, and experience higher rates of recurrent CDI (rCDI). However, it is still not clear whether rCDI is a cause of refractory IBD or a consequence of the inflammatory state in the colon. Aims We aimed to assess the outcomes of rCDI in patients with active IBD compared to inactive IBD in the era of fecal microbiota transplantation (FMT) Methods This is a retrospective cohort of adult IBD patients with rCDI at the IBD centre at the University of Alberta hospital between 2014–2017. rCDI was defined as a recurrent episode occurring within 60 days of the prior after successful treatment with antibiotics. We collected demographic and clinical characteristics, along with the rCDI-related and FMT outcomes in patients with active and inactive IBD. Active IBD was based on clinical assessment using a combination of disease severity scores (Harvey Bradshaw Index, partial Mayo scores), presence of active disease on colonoscopy, clinical symptoms and/or treatment escalation or change in the month leading up to rCDI diagnosis. Results Over the study period, 56 IBD patients (50% ulcerative colitis, 28/56) had a total of 85 rCDI episodes. Thirty-four percent (19/56) of patients had two or more rCDI episodes. Forty-one percent (35/85) of rCDI episodes were toxin positive while the remainder were only PCR positive. Thirty-nine percent (33/85) had active IBD at the time of CDI diagnosis. Patients with active IBD were more likely to have rCDI (1.7 rCDI episodes vs. 1.5, p=0.018). IBD treatment escalation was also more likely in the active IBD cases (79% vs. 44%, p = 0.002) with the use of steroids (27% vs 2%, p = 0.001) and addition of biologics (18% vs. 2%, p = 0.013). Active IBD cases were also more likely to be hospitalized (30% vs. 10%, p = 0.02) and were more likely to receive FMT (27% vs. 4%, p = 0.003). There was no difference in the time between rCDI episodes, antibiotic exposure or colectomy rates between the two groups. Conclusions Compared to IBD patients in remission, patients with active IBD are more likely to experience rCDI, IBD treatment escalation and FMT. It is interesting to note that only 27% of patients with recurrent CDI required FMT suggesting CDI may be a marker of active or refractory disease rather than a cause. Larger, prospective studies are needed to help clarify this association. Funding Agencies None

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.

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