Microbial Transformation of Dietary Glycerol Contributes to Intestinal Acrolein Formation and Urinary Excretion

The aldehyde acrolein has been associated with diabetes, cardiovascular, respiratory, and neurodegenerative diseases, and gut microbiota possesses the potential for acrolein release via the key enzyme glycerol/diol dehydratase (PduCDE). This study aimed at estimating the contribution of gut microbiota to endogenous acrolein production. To minimize confounding sources, we investigated the intestinal acrolein-producing potential of 20 volunteers housed under defined conditions. Glycerol was present in every meal and was detected in feces, suggesting availability to intestinal microbiota. Based on fecal metagenomics and pduC analysis, all volunteers showed potential for intestinal glycerol transformation to acrolein; the genus Anaerobutyricum was the major contributor across donors and time. Levels of urine biomarkers N-acetyl-S-(3-hydroxypropyl)-L-cysteine (3-HPMA) and N-acetyl-S-(carboxyethyl)-L-cysteine (CEMA) were higher after the consumption of meals with high glycerol levels, suggesting immediate microbial transformation to acrolein. Only a small proportion of acrolein metabolites was recovered in urine, possibly due to high compound reactivity. Donors could be separated into 3-HPMA or CEMA phenotypes based on the predominance of urine biomarkers, and phenotypes related to overall fecal microbiota and fermentation metabolite profiles. Our data show that oral fat/glycerol intake together with intestinal microbiota activity might temporarily increase endogenous acrolein formation and that urinary biomarkers link to the intestinal microbiome.