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.

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 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.

Clostridium Difficile Infection in Inflammatory Bowel Disease Patients

2019 ◽  
Vol 19 (7) ◽  
pp. 929-935
Author(s):  
Abdulmajeed A. Albarrak ◽  
Bhupinder S. Romana ◽  
Suleyman Uraz ◽  
Mohamad H. Yousef ◽  
Alhareth A. Juboori ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Clostridium Difficile ◽  
Clostridium Difficile Infection ◽  
Bowel Disease ◽  
Health Care Organizations ◽  
Fecal Microbiota ◽  
Fecal Microbiota Transplant ◽  
Expert Review ◽  
Inflammatory Bowel ◽  
High Index Of Suspicion

Background:The rising incidence of Clostridium difficile infection (CDI) in the general population has been recognized by health care organizations worldwide. The emergence of hypervirulent strains has made CDI more challenging to understand and treat. Inflammatory bowel disease (IBD) patients are at higher risk of infection, including CDI.Objective:A diagnostic approach for recurrent CDI has yet to be validated, particularly for IBD patients. Enzyme immunoassay (EIA) for toxins A and B, as well as glutamate dehydrogenase EIA, are both rapid testing options for the identification of CDI. Without a high index of suspicion, it is challenging to initially differentiate CDI from an IBD flare based on clinical evaluation alone.Methods:Here, we provide an up-to-date review on CDI in IBD patients. When caring for an IBD patient with suspected CDI, it is appropriate to empirically treat the presumed infection while awaiting further test results.Results:Treatment with vancomycin or fidaxomicin, but not oral metronidazole, has been advocated by an expert review from the clinical practice update committee of the American Gastroenterology Association. Recurrent CDI is more common in IBD patients compared to non-IBD patients (32% versus 24%), thus more aggressive treatment is recommended for IBD patients along with early consideration of fecal microbiota transplant.Conclusion:Although the use of infliximab during CDI has been debated, clinical experience exists supporting its use in an IBD flare, even with active CDI when needed.

scholarly journals Dynamic Colonization of Microbes and Their Functions after Fecal Microbiota Transplantation for Inflammatory Bowel Disease

mBio ◽  
2021 ◽  
Author(s):  
Nathaniel D. Chu ◽  
Jessica W. Crothers ◽  
Le T. T. Nguyen ◽  
Sean M. Kearney ◽  
Mark B. Smith ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Immune System ◽  
Bowel Disease ◽  
Healthy Donor ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Complex Mixtures ◽  
Sick Patient ◽  
Inflammatory Bowel ◽  
Living Organisms

Fecal microbiota transplantation (FMT)—transferring fecal microbes from a healthy donor to a sick patient—has shown promise for gut diseases such as inflammatory bowel disease. However, unlike pharmaceuticals, fecal transplants are complex mixtures of living organisms, which must then interact with the microbes and immune system of the recipient.

Outcomes of Fecal Microbiota Transplantation for C. difficile Infection in Inflammatory Bowel Disease

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Raseen Tariq ◽  
Tausif Syed ◽  
Devvrat Yadav ◽  
Larry J. Prokop ◽  
Siddharth Singh ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Inflammatory Bowel
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