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Oral FMT with antibiotics does not improve symptoms of IBS-D
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SAN DIEGO — Orally delivered fecal microbiota transplantation did not help reduce symptoms in patients with diarrhea-predominant irritable bowel syndrome whether or not they were pre-treated with antibiotics, according to data presented at Digestive Disease Week.
Prashant Singh, MD, of the department of gastroenterology at Beth Israel Deaconess Medical Center, said that gut dysbiosis could be a critical factor in the development of IBS-D, and while FMT treatment for IBS has been the subject of many studies, they have led to conflicting results.
“We don’t know the best technique to administer FMT to bring the long-lasting stool engraftment,” Singh said in his presentation. “It is also unclear if antibiotic treatment prior to FMT has an impact on GI symptoms or engraftment of the fecal microbiota transplant.”
Researchers conducted a double-blind, placebo-controlled trial comprising 44 patients with moderate to severe IBS-D, defined as IBS severity scoring system (IBS-SSS) 175 or greater. They randomly assigned patients to four groups; FMT alone (n = 11), FMT following a 7-day pre-treatment course of ciprofloxacin and metronidazole (n = 10), FMT following a 7-day pre-treatment course of rifaximin (n = 11), or a placebo FMT (n = 12).
Investigators assessed IBS-SSS, quality of life (IBS-QOL), IBS-Global improvement scale (IBS-GIS) and adequate symptom relief at week 1 and week 10.
Patients in all four groups experienced similar changes in IBS-SSS scores from baseline to week 1 and 10. A comparable proportion of patients in all four groups also experienced adequate relief, mean IBS-GIS and change in IBS-QOL scores at both time points.
The change in IBS-SSS scores from baseline was also comparable in the three FMT groups combined, compared with placebo.
“Pre-treatment with antibiotics before FMT did not have any significant impact on clinical outcomes in IBS-D patients,” Singh concluded. “At this time, we are looking at the microbiome data from week 1 and week 10 and comparing them with baseline to see if we can correlate the changes in microbiome with symptom improvement.” – by Alex Young
Reference:
Singh P, et al. Abstract 1,101. Presented at: Digestive Disease Week; May 18-21, 2019; San Diego.
Disclosures: Singh reports no relevant financial disclosures. Please see the meeting disclosure index for all other authors’ relevant financial disclosures.
Perspective
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William D. Chey, MD
The role of the gut microbiome in the pathogenesis and treatment of IBS is increasingly recognized. The observation that an acute gastroenteritis increases the likelihood of developing IBS as well as the identification of intrinsic differences in the microbiome of IBS patients relative to healthy controls support the suggestion that disturbances in the microbiome can lead to IBS.
Further, multiple microbiome-based treatments including diet, prebiotics, probiotics and antibiotics have been found to be beneficial for subsets of patients with IBS. Successes with these treatments have stoked speculation about the potential benefits of fecal microbial transplant (FMT) as a treatment for IBS patients. The stunning success of FMT for patients with recurrent C. difficile infection has further fanned the flames around this debate.
Indeed, multiple randomized controlled trials (RCTs) have assessed FMT vs. sham FMT in IBS patients. The results have been summarized in two recently published meta-analyses. In the meta-analysis by Xu et al, when data from four RCTs was aggregated, FMT was found to be no more effective than sham FMT (RR = 0.93; 95% CI, 0.48–1.79). The second meta-analysis by Ford et al came to a similar conclusion based upon data from five RCTs.
However, in an analysis based on mode of administration of FMT, it was found that colonoscopic administration offered benefits for IBS (RR = 0.98; 95% CI, 0.58–1.66) while FMT administered as oral capsules or naso-jejunal tube did not. As none of the trials directly compared the different modes of FMT administration and other factors (eg, donor, dose, timing of administration), the results of this post-hoc, subgroup analysis should be viewed as hypothesis generating and will require confirmation in a properly designed and powered, comparative effectiveness trial.
The small study by Singh et al adds to this growing body of literature. This study casts doubt on the benefit of pre-FMT antibiotics. Additionally, this study provides further evidence against the value of FMT using oral capsules for IBS. For now, FMT for IBS should be considered experimental. More studies are needed to determine if colonoscopically administered FMT is beneficial IBS. It will also be interesting and important to explore whether profiling of the gut microbiome or metabolome might serve as a biomarker that could enrich the likelihood of response to FMT and more generally, microbiome-based treatments.
References
Barbara G, et al. Gastroenterol. 2016;doi:10.1053/j.gastro.2016.02.028.
Ianiro G, et al. Aliment Pharmacol Ther. 2019;doi:10.1111/apt.15330.
Menees S, et al. F1000Research. 2018;doi:10.12688/f1000research.14592.1.
Shin A, et al. Clin Gastro Hepatol. 2019;doi:10.1016/j.cgh.2018.08.054.
Xu D, et al. Am J Gastroenterol. 2018;10.14309/ajg.0000000000000198.
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