DAY 1: The Role of the Gut Microbiome in IBD and the Therapeutic Potential of FMT

Kusalik Boppana, MBBS, from Kasturba Medical College of Manipal, conducted a systematic review of the literature to assess the use of gut microbiome dysbiosis as a diagnostic marker of early IBD. The analysis included 20 studies of 2,713 individuals with IBD and 1,976 healthy controls; 17 studies reported significantly reduced microbiome alpha diversity, and 12 studies reported differing beta diversity between those with early IBD (prior to symptoms) and controls. Depletion of beneficial microbes, such as Bacterioidetes, and enrichment of pathogenic microbes, such as Escherichia coli, were found in 14 studies. Reduced Blautia and Coprococcus microbes were reduced in patients with early Crohn’s disease (CD). The authors concluded that microbiome profiling may be useful for detecting those at risk of IBD, though more prospective studies are needed. (P1026)

Edward L. Barnes, MD, MPH, from the University of North Carolina at Chapel Hill, reported on the effect of the live biotherapeutic EXE-346 on bowel movement frequency in subjects with an ileal pouch-anal anastomosis (IPAA). EXE-346 is a biologic-grade formulation of the food-grade probiotic Visibiome®. A total of 10 patients from 4 centers in the US with IPAA and an average of at least 10 bowel movements per day during a 7-day period were treated twice daily with EXE-346 for 4 weeks. Median bowel frequency decreased 23% from 11.7 per day to 9.1 per day and nighttime bowel frequency decreased 48% from 2.3 to 1.2 after 4 weeks of treatment. Mild side effects were seen in 4 patients and included decreased appetite, rash, elevated serum calcium, and hepatic steatosis. A placebo-controlled phase 2 study of EXE-346 is ongoing. (P3287)

Four systematic reviews/metanalyses examined the use of FMT in IBD, producing consistent evidence that FMT improves clinical and endoscopic outcomes, particularly in non-refractive disease.

Arthur Chidi Igbo, MD, MPH, from Texas Health Resources HEB/Denton Internal Medicine Program, analyzed 6 randomized controlled trials evaluating the effect of FMT in patients with refractory ulcerative colitis (UC), defined as persistent activity despite optimized therapy with corticosteroids, immunosuppressants, or biologic therapies. They found no benefit of FMT over control interventions for the endpoints of clinical remission or endoscopic remission. These findings contrast with previous studies showing a benefit of FMT in non-refractory UC, and suggest that refractory disease likely requires combination treatment strategies beyond microbial manipulation. (P1128)

Panagiotis G. Doukas, MD, from Saint Peter’s University Hospital, Rutgers Robert Wood Johnson Medical School, examined the efficacy and safety of FMT in 15 randomized controlled trials of adults with UC, without limitations on the severity of disease. Compared to controls, FMT significantly improved both clinical remission (62% FMT vs. 50.5% controls) and endoscopic remission (42% FMT vs. 22% controls), with no difference in adverse events between groups. (P1137)

Rahul Tripathi, MD, from Stony Brook Medicine, examined the effect of FMT in 17 randomized clinical trials including 802 patients with UC. FMT was associated with significantly higher rates of clinical remission compared to control (RR=1.53, 95% CI 1.17-2.00; P=0.0019), and of the 6 studies with endoscopic data, FMT had higher rates of endoscopic improvement compared to controls (RR=1.72, 95% CI 1.23-2.39; P=0.0013). GI adverse events (n=10 studies) were the same between FMT and control groups. (P3260)

In the final meta-analysis, Prince Shah-Riar, MD, from DHR Health, examined remission and mucosal healing outcomes in 7 randomized controlled trials of patients with IBD, including both CD and UC. The clinical remission rate was statistically significantly higher with FMT than control and mucosal healing was seen in 38.2% of patients in the FMT group compared to 24.6% of controls. No difference in serious adverse events was seen between the two groups. (P5356)