Abnormal bowel movement frequency may be associated with elevated uremic toxins and reduced kidney and liver function in healthy individuals, according to a new study.
In the study, published in Cell Reports Medicine, researchers from the Institute for Systems Biology and Phenome Health analyzed multi-omic data and collected the stool and blood samples from 1,425 participants who completed extensive diet, health, and lifestyle questionnaires. The participants were predominantly White females from the U.S. West Coast. The researchers utilized 16S rRNA gene amplicon sequencing for gut microbiome analysis, untargeted metabolomics for blood metabolite measurement, and standard clinical tests for organ function assessment.
The researchers defined normal bowel movement frequency as one to three bowel movements per day, constipation as two or less bowel movements per week, and diarrhea as four or more bowel movements per day.
Constipation was found to be correlated with higher blood levels of uremic toxins such as p-cresol sulfate, phenylacetylglutamine, p-cresol glucuronide, and indoxyl sulfate as well as reduced kidney function (lower estimated glomerular filtration rate). These uremic toxins, particularly p-cresol sulfate, have previously been implicated in the progression of chronic kidney disease. Diarrhea was associated with elevated biomarkers of liver dysfunction like bilirubin. Both conditions showed altered gut microbiome composition, including depletion of beneficial short-chain fatty acid–producing bacteria and enrichment of bacteria involved in protein fermentation and toxin production.
A causal mediation analysis suggested that indoxyl sulfate (3-IS) may partially mediate the relationship between lower bowel movement frequencies and reduced kidney function—indicating that uremic toxin accumulation may precede organ damage in chronic constipation.
Dietary and lifestyle factors associated with bowel movement frequencies included:
- Lower fruit and vegetable intake in participants with low-normal bowel movement frequencies
- Higher likelihood of snacking in participants with low-normal bowel movement frequencies
- Marginal association between a history of depression and anxiety and abnormal bowel movement frequencies.
The study's limitations included demographic homogeneity, which may have affected generalizability.
The researchers suggested that managing bowel movement frequencies through diet and lifestyle modifications could potentially reduce chronic disease risk, particularly chronic kidney disease. However, further research may be needed to establish causality and develop targeted interventions.
A declaration of interests is available in the original study.