Chronic oral exposure to didecyldimethylammonium chloride induces region-specific intestinal dysfunction and gut microbiota remodeling in mice

Abstract

bstract Didecyldimethylammonium chloride (DDAC) is a widely used quaternary ammonium disinfectant, but its effects on intestinal physiology following chronic oral exposure remain poorly understood. Here, we investigated the impact of chronic dietary DDAC exposure on intestinal function, gut microbial composition, and microbiota-related metabolites in mice. After 12 weeks of exposure, DDAC induced distinct intestinal phenotypes depending on exposure level. Exposure to 32.5 ppm DDAC increased intestinal permeability and was associated with reduced ileal mucus content and decreased expression of barrier-related genes in both the ileum and colon, whereas exposure to 130 ppm DDAC induced colon shortening, colonic mucus depletion, and histological remodeling. Notably, several intestinal alterations were observed at estimated exposure levels below the reported no-observed-adverse-effect level, highlighting intestinal endpoints as potentially sensitive measures of chronic DDAC exposure that warrant further investigation. Cecal microbiota analysis revealed substantial shifts in microbial community structure despite minimal effects on alpha diversity. Multivariable association analysis identified DDAC-responsive microbial features associated with host intestinal phenotypes after adjustment for DDAC treatment group. Among these, a Lactobacillus -associated amplicon sequence variant (ASV) was positively associated with colon length, whereas a Duncaniella -associated ASV was inversely associated with colonic histological score. Collectively, these findings demonstrate that chronic oral DDAC exposure induces region-specific intestinal dysfunction accompanied by microbial community remodeling. These results identify intestinal endpoints that may be sensitive to chronic DDAC exposure and suggest that microbiota remodeling may accompany the observed intestinal effects.