Aberrant bowel movement frequencies coincide with increased microbe-derived blood metabolites associated with reduced organ function.

The total effect of the overall model did not quite pass our significance threshold of alpha <0.05 (total effect, p = 0.064), but we saw a significant average direct effect (ADE) of BMF on eGFR (ADE = −4.458, p = 0.012) and a highly significant average causal mediation effect (ACME) of BMF via 3-IS on eGFR (ACME = 1.343, p < 2E−16; Figure 7 B).

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After logistic regression, 3 “true or false”-response questions related to history of depression in self and family history appeared marginally significant (logistic regression, FDR-corrected p < 0.1), with a self-reported “true” response to a “family history of depression” showing a marginal association with constipation (logistic regression, FDR-corrected <0.1), a self-reported “true” response to a “sibling history of depression” showing a significant association with diarrhea (logistic regression, FDR-corrected <0.05), and a self-reported “true” response to “recent ailments in self-history of depression” showing a marginal association with low-normal BMF (logistic regression, FDR-corrected <0.1).

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The annotated metabolites tended to show a decreasing trend with increasing BMF, while the unannotated metabolites and 3-IS showed more varied relationships (e.g., monotonic and non-monotonic) with BMF ( Figures 5 and S3 ).

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