Plasma acetic acid mediates the relationship between gut microbiome and various health measures in older adults

Short-chain fatty acids are believed to mediate microbiome-host interactions. Acetic acid is the most abundant systemic short-chain fatty acid, but knowledge about its physiological functions comes mainly from rodent experiments, with limited human research particularly in the aging population.

In this cross-sectional observational study, we examined the association between the gut microbiota and plasma acetic acid, specifically investigating the mediating effect of plasma acetic acid on the relationship between the gut microbiota and blood lipid profile, body composition, brain gray matter volume, and cognitive performance in older adults. The gut microbiome was profiled using full-length 16S rRNA gene sequencing to enable taxonomic classification.

Here we show that specific gut microbial co-abundance group is associated with plasma acetic acid levels. Higher plasma levels of acetic acid are associated with lower plasma triglyceride levels, higher high-density lipoprotein cholesterol levels, lower body mass index, lower body fat mass, higher thalamic volume, and higher cognitive performance in certain domains. Additionally, we show that plasma acetic acid mediates the relationship between gut microbiome on these health measures.

This study identifies gut microbial group linked to plasma acetic acid and demonstrates its potential mediating role between the gut microbiome, blood lipid profile, brain volume and cognitive function in older adults. These insights pave the way for future research and highlight the potential of acetic acid as an intervention target for metabolic and neurological diseases, contributing to strategies that promote healthy aging.