Metabolic, Epigenetic, and Transgenerational Effects of Gut Bacterial Choline Consumption

Abstract: Choline is an essential nutrient and methyl donor required for epigenetic regulation. Here, we assess the impact of gut microbial choline metabolism on bacterial fitness and host biology by engineering a microbial community to lack a single choline-utilizing enzyme. Our results indicate that choline-utilizing bacteria compete with the host for this nutrient, significantly impacting plasma and hepatic levels of methyl-donor metabolites recapitulating biochemical signatures of choline deficiency. Mice harboring high levels of choline-consuming bacteria show increased susceptibility to metabolic disease. Furthermore, bacterially-induced reduction of methyl-donor availability alters global DNA methylation patterns in both adult mice and their offspring in utero and engenders anxious behavior. Altogether, our results reveal an underappreciated aspect of bacterial choline metabolism (i.e., methyl-donor depletion) that is linked to alterations in metabolism, epigenetics, and behavior. More broadly, this work suggests that interpersonal differences in microbial metabolism should be considered when determining optimal levels of nutrient intake. 8 samples in total (biological n=4 per for each defined community; 9kw old female C57BL/6 mouse liver; 2 weeks of colonization and maintenance on 1% choline diet; 4hours of fasting prior to sacrifice)