Modulating effects of microbiota on synbiotic intervention outcomes for microbiota-derived trimethylamine, trimethylamine N-oxide and indoxyl sulfate in healthy young medical students: insights from a 12-week randomized clinical trial.

Regarding the effect of time on alpha diversity across the study, only richness showed a trend towards significance ( P = 0.016, P adj =0.016, Q = 0.066), while Shannon ( P = 0.404, P adj =0.413, Q = 0.827), evenness ( P = 0.680, P adj =0.674, Q = 0.895), and Simpson index ( P = 0.874, P adj =0.895, Q = 0.895) demonstrated no significant changes.

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Although K14084 (mttC, trimethylamine corrinoid protein) and K16176 mtmB methylamine-corrinoid protein Co-methyltransferase) showed similar response patterns with lower baseline abundance was associated with a favorable response, indicated by a decrease in TMA levels over time, these associations t did not reach statistical significance (K14084: LRT P = 0.236, Padj = 0.143, Fig. 5 A, middle panel, K16176: LRT P = 0.254, P adj =0.153, Fig. 5 A, lower panel).

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In contrast, no significant interactions were found after FDR correction for models assessing Bray-Curtis distances and pathway-level beta-diversity for all microbiota-derived metabolites, though some results approached marginal significance, such as Bray-Curtis genus-level for log-indoxyl sulfate (P adj =0.055, Q = 0.354, Additional file 1 , Supplementary Fig. 4 B).

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Similarly, while ASV- and KO-based WGCNA modules did not demonstrate significant correlations with baseline metabolite levels, the KO-based green module showed a nominally significant negative association with indoxyl sulfate.

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