Impact of Triacetin- and Tributyrin-Based Formulations on IBS Microbiome Composition and SCFA Profiles: A Preclinical Study.

Irritable bowel syndrome (IBS) is a prevalent yet poorly understood functional gut disorder frequently associated with microbial dysbiosis, making microbiome-targeting interventions a promising management strategy. In this study, we evaluated the microbiome-modulating potential of three doses of triacetin (TA; ReBiome™; 100, 200 and 300 mg/day) and two finished formulations containing TA and/or tributyrin (TB): Active Biome™ (AB) and Bio Complete 3™ (BC3). Inulin served as a benchmark prebiotic. The validated ex vivo Systemic Intestinal Fermentation Research (SIFR®) technology pipeline was applied using fecal microbiota from eight adults with IBS. TA dose-dependently increased short-chain fatty acid (SCFA) levels from 100 mg/day, significantly increasing acetate and butyrate while maintaining low gas formation. In addition to acetate and butyrate, AB and BC3 also promoted propionate while BC3 induced a particularly pronounced butyrate increase. Overall, both formulations induced stronger SCFA but milder gas increases than inulin. TA, AB and BC3 enriched IBS-depleted, butyrate-associated OTUs related to Faecalibacterium and Anaerobutyricum species. AB and BC3 increased microbial diversity (community modulation score (CMS)) by promoting Bifidobacteriaceae, Lachnospiraceae and Bacteroidaceae. Overall, TA and TA/TB-containing formulations promoted butyrate production, potentially helping mitigate IBS symptom severity by inducing a favorable fermentation profile with limited gas formation.