Bifidobacterium breve Bif195 Protects Against Small-Intestinal Damage Caused by Acetylsalicylic Acid in Healthy Volunteers

Abstract

Bifidobacterium breve Bif195 Protects Against Small-intestinal Damage Caused by Acetylsalicylic Acid in Healthy Volunteers A randomized, placebo-controlled, double-blind clinical trial Aspirin + Bif195 Aspirin + Placebo = 31 Bif195 Placebo = 35 Aspirin Bif195 / Placebo See Covering the Cover synopsis on 587. BACKGROUND & AIMS: Enteropathy and small-intestinal ulcers are common adverse effects of nonsteroidal antiinflammatory drugs such as acetylsalicylic acid (ASA). Safe, cytoprotective strategies are needed to reduce this risk. Specific bifidobacteria might have cytoprotective activities, but little is known about these effects in humans. We used serial video capsule endoscopy (VCE) to assess the efficacy of a specific Bifidobacterium strain in healthy volunteers exposed to ASA. METHODS: We performed a single-site, double-blind, parallelgroup, proof-of-concept analysis of 75 heathy volunteers given ASA (300 mg) daily for 6 weeks, from July 31 through October 24, 2017. The participants were randomly assigned (1:1) to groups given oral capsules of Bifidobacterium breve (Bif195) (!5 Â 10 10 colony-forming units) or placebo daily for 8 weeks. Small-intestinal damage was analyzed by serial VCE at 6 visits. The area under the curve (AUC) for intestinal damage (Lewis score) and the AUC value for ulcers were the primary and first-ranked secondary end points of the trial, respectively. RESULTS: Efficacy data were obtained from 35 participants given Bif195 and 31 given placebo. The AUC for Lewis score was significantly lower in the Bif195 group (3040 ± 1340 arbitrary units) than the placebo group (4351 ± 3195) (P ¼ .0376). The AUC for ulcer number was significantly lower in the Bif195 group (50.4 ± 53.1 arbitrary units) than in the placebo group (75.2 ± 85.3 arbitrary units) (P ¼ .0258). Twelve adverse events were reported from the Bif195 group and 20 from the placebo group. None of the events was determined to be related to Bif195 intake. CONCLUSIONS: In a randomized, double-blind trial of healthy volunteers, we found oral Bif195 to safely reduce the risk of small-intestinal enteropathy caused by ASA. ClinicalTrials.gov no: NCT03228589.

Current knowledge on non-steroidal anti-inflammatory drug-induced small-bowel damage: a comprehensive review

“…In a small-scale randomized trial, Endo et al reported that L. casei reduced small-bowel endoscopic injury among chronic NSAID users [103]. Recently, a double-blind randomized trial of healthy volunteers showed a significant reduction in LDAinduced small-bowel mucosal injury with oral Bifidobacterium breve (Bif195) [122]. To identify whether there are specific patterns of microbial profile among chronic NSAID users, we need to use bioinformatics to identify subpopulations that are associated with certain phenotypes (e.g., bleeding, stricture, and protein-losing enteropathy).…”

Nutraceuticals as modulators of gut microbiota: Role in therapy

“…Indeed, effects of an orally administered probiotic on the systemic immune system (Groeger et al, ; Konieczna, Akdis, Quigley, Shanahan, & O'Mahony, ) and on brain responses (Pinto‐Sanchez et al, ; Wang, Braun, Murphy, & Enck, ) have, indeed, been demonstrated in human studies. Clinically relevant protective effects of a probiotic against acetylsalicylic acid‐induced intestinal injury have also been demonstrated in the absence of any discernible change in the gut microbiota (Mortensen et al, ). These and other observations indicate that probiotic effects are subtle and not readily discernible by the more widely available high‐throughput sequencing platforms.…”

Letter: synergistic role of gut flora with aspirin to prevent colorectal cancers

“…Furthermore, aspirin resistance might also hinder the expanded clinical use of aspirin in the population, which could be caused by abundance of some aerobic gut microbes degrading aspirin and decreasing its plasma levels. 3 Gut flora modulation could be synergistic with aspirin in reducing CRC risk as follows: probiotics could be used to reduce the risk of small intestinal enteropathy caused by aspirin, 5 and use of specific probiotics, prebiotics or faecal microbiota transplantation could alleviate or reverse aspirin resistance by targeted modulations. 3,6 Finally, re-setting the inflammatory microenvironment by inhibiting the formation of trimethylamine N-oxide, a gut microbial metabolite and CRC risk factor, 7,8 could delay or stop the adenoma-cancer progression.…”