scholarly journals Therapeutic Advances in Gut Microbiome Modulation in Patients with Inflammatory Bowel Disease from Pediatrics to Adulthood

2021 ◽  
Vol 22 (22) ◽  
pp. 12506
Author(s):  
Adi Eindor-Abarbanel ◽  
Genelle R. Healey ◽  
Kevan Jacobson
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Gut Microbiome ◽  
High Throughput Sequencing ◽  
Fecal Microbiota ◽  
Fecal Microbiota Transplant ◽  
Intestinal Microbes ◽  
New Therapeutic Approaches ◽  
Microbiome Research ◽  
Inflammatory Bowel

There is mounting evidence that the gut microbiota plays an important role in the pathogenesis of inflammatory bowel disease (IBD). For the past decade, high throughput sequencing-based gut microbiome research has identified characteristic shifts in the composition of the intestinal microbiota in patients with IBD, suggesting that IBD results from alterations in the interactions between intestinal microbes and the host’s mucosal immune system. These studies have been the impetus for the development of new therapeutic approaches targeting the gut microbiome, such as nutritional therapies, probiotics, fecal microbiota transplant and beneficial metabolic derivatives. Innovative technologies can further our understanding of the role the microbiome plays as well as help to evaluate how the different approaches in microbiome modulation impact clinical responses in adult and pediatric patients. In this review, we highlight important microbiome studies in patients with IBD and their response to different microbiome modulation therapies, and describe the differences in therapeutic response between pediatric and adult patient cohorts.

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.

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 Human Gut Microbiome Transplantation in Ileitis Prone Mice: A Tool for the Functional Characterization of the Microbiota in Inflammatory Bowel Disease Patients

2019 ◽  
Author(s):  
Abigail R Basson ◽  
Adrian Gomez-Nguyen ◽  
Paola Menghini ◽  
Ludovica F Buttó ◽  
Luca Di Martino ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Mouse Model ◽  
Bowel Disease ◽  
Gut Microbiome ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Human Gut ◽  
Variable Effect ◽  
Inflammatory Bowel ◽  
Anti Inflammatory

Abstract Background Inflammatory bowel disease (IBD) is a lifelong digestive disease characterized by periods of severe inflammation and remission. To our knowledge, this is the first study showing a variable effect on ileitis severity from human gut microbiota isolated from IBD donors in remission and that of healthy controls in a mouse model of IBD. Methods We conducted a series of single-donor intensive and nonintensive fecal microbiota transplantation (FMT) experiments using feces from IBD patients in remission and healthy non-IBD controls (N = 9 donors) in a mouse model of Crohn’s disease (CD)-like ileitis that develops ileitis in germ-free (GF) conditions (SAMP1/YitFC; N = 96 mice). Results Engraftment studies demonstrated that the microbiome of IBD in remission could have variable effects on the ileum of CD-prone mice (pro-inflammatory, nonmodulatory, or anti-inflammatory), depending on the human donor. Fecal microbiota transplantation achieved a 95% ± 0.03 genus-level engraftment of human gut taxa in mice, as confirmed at the operational taxonomic unit level. In most donors, microbiome colonization abundance patterns remained consistent over 60 days. Microbiome-based metabolic predictions of GF mice with Crohn’s or ileitic-mouse donor microbiota indicate that chronic amino/fatty acid (valine, leucine, isoleucine, histidine; linoleic; P < 1e-15) alterations (and not bacterial virulence markers; P > 0.37) precede severe ileitis in mice, supporting their potential use as predictors/biomarkers in human CD. Conclusion The gut microbiome of IBD remission patients is not necessarily innocuous. Characterizing the inflammatory potential of each microbiota in IBD patients using mice may help identify the patients’ best anti-inflammatory fecal sample for future use as an anti-inflammatory microbial autograft during disease flare-ups.

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 Fecal microbiota transplant – a new frontier in inflammatory bowel disease

2018 ◽  
Vol Volume 11 ◽  
pp. 321-328 ◽  
Author(s):  
Tagore Sunkara ◽  
Prashanth Rawla ◽  
Andrew Ofosu ◽  
Vinaya Gaduputi
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Fecal Microbiota ◽  
Fecal Microbiota Transplant ◽  
New Frontier ◽  
Inflammatory Bowel

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.

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