Aberrant bowel movement frequencies coincide with
increased microbe-derived blood metabolites
associated with reduced organ function
Highlights
- BMF variation impacts the gut microbiota and blood
metabolome in a healthy cohort - Aberrant BMF associates with microbially derived toxins in
blood and with inflammation - Indoxyl sulfate linked to constipation and negatively
associates with kidney function - Diet, lifestyle, and cognitive factors are associated with BMF variation
SUMMARY
Bowel movement frequency (BMF) directly impacts the gut microbiota and is linked to diseases like chronic kidney disease or dementia. In particular, prior work has shown that constipation is associated with an ecosystem-wide switch from fiber fermentation and short-chain fatty acid production to more detrimental protein fermentation and toxin production. Here, we analyze multi-omic data from generally healthy adults to see how BMF affects their molecular phenotypes, in a pre-disease context. Results show differential abundances of gut microbial genera, blood metabolites, and variation in lifestyle factors across BMF categories.
These differences relate to inflammation, heart health, liver function, and kidney function. Causal mediation analysis indicates that the association between lower BMF and reduced kidney function is partially mediated by the microbially derived toxin 3-indoxyl sulfate (3-IS). This result, in a generally healthy context, suggests that the accumulation of microbiota-derived toxins associated with abnormal BMF precede organ damage and may be drivers of chronic, aging-related diseases.
