Associations of colonic transit with the gut microbiota and short-chain fatty acids in health and irritable bowel syndrome

Gut bacteria are known to influence short-chain fatty acid (SCFA) levels through direct metabolic activity. Colonic transit also affects substrate contact time, fermentation duration, and SCFA absorption. But it is unclear whether some bacteria influence SCFA levels indirectly, by altering transit, rather than only directly, and whether this differs across health and irritable bowel syndrome (IBS) subtypes. Using data from 56 participants [17 healthy volunteers (HV), 15 IBS-C, 24 IBS-D] with concurrent stool metagenomes, stool SCFA, and segmental colonic transit measurements, we applied mediation analysis to test whether each bacterial taxon's association with SCFA levels may be transit-mediated statistically. Three taxa showed a potential transit-mediated association with at least one SCFA: Faecalibacterium prausnitzii in HV, Bacteroides thetaiotaomicron in IBS-C, and Phascolarctobacterium succinatutens in IBS-D. For F. prausnitzii, the transit-mediated pathway was the only detectable association with SCFA. The remaining two taxa, B. thetaiotaomicron and P. succinatutens, additionally showed a direct, transit-independent effect alongside the transit-mediated one. Separately, an analysis of direct, non-mediated effects identified 15 additional taxa (5 in HV, 2 in IBS-C, and 8 in IBS-D) whose associations with SCFA levels were not explained by colonic transit. Together, these findings suggest that colonic transit may potentially mediate specific associations between gut bacteria and SCFA levels, in addition to the direct metabolic effects of the bacteria. However, because the present study is cross-sectional, these findings should be interpreted as statistical associations rather than established biological or directional relationships. In addition, this was an exploratory post-hoc analysis of a single relatively small cohort, and independent validation will be required before the biological or clinical significance of these findings can be established.