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Multi-Species Synbiotic Supplementation Enhances Gut Microbial Diversity, Increases Urolithin A and Butyrate Production, and Reduces Inflammation in Healthy Adults: A Randomized, Placebo-Controlled Trial

Brooke A Napier, J. Allegretti, P. Feuerstadt, Colleen R. Kelly, Nicholas W. Van Hise, R. Jäger, Z. Kassam, Gregor Reid

Nutrients, 2025

32 participants · 21 citations

Abstract

Background: In healthy adults, probiotic supplementation alone does not increase Urolithin A (UroA) and rarely increases butyrate, both microbiome-derived metabolites that influence key biological functions involved in regulating gastrointestinal symptoms. Accordingly, this clinical trial evaluated key biological functions of a multi-species synbiotic with 24 probiotic strains and a polyphenol-based prebiotic using capsule-in-capsule delivery technology. Methods: We conducted a randomized, placebo-controlled trial among healthy participants (n = 32). Participants were administered a daily synbiotic (53.6 billion AFU multi-species probiotic and 400 mg Indian pomegranate extract; DS-01) or matching placebo for 91 days. Samples were obtained at baseline Day 0, and Days 7, 14, 49, and 91. Endpoints included changes in fecal microbiome composition, urinary UroA, fecal butyrate, serum CRP, and safety. Results: The synbiotic significantly increased alpha-diversity of Bifidobacterium and Lactobacillus spp. at all timepoints, including at end-of-study (Day 91, p < 0.0001) and increased native beneficial microbes. UroA production was significantly increased in the synbiotic arm at short-term (Day 7, 12-fold, p < 0.02) and long-term (Day 91, 49-fold, p < 0.001) timepoints. A higher proportion of synbiotic participants were capable of converting polyphenols into UroA (Day 91, 100% vs. 44.4%; p < 0.01). Mechanistically, synbiotic participants showed an increased abundance of…

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Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 32 participants or records.

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