Metabolic landscape of the male mouse gut identifies different niches determined by microbial activities

Distinct niches of the mammalian gut are populated by diverse microbiota, but the contribution of spatial variations to intestinal metabolism remains largely unclear. We mapped out the longitudinal metabolome along the gut of healthy colonized and germ-free male mice and identified a general shift from amino acids in the small intestine to organic acids, vitamins, and nucleotides in the large intestine. Comparing metabolic landscapes in colonized versus germ-free mice allowed us to disentangle the origin of many metabolites in different niches, in some cases inferring underlying processes or producing species. Beyond the known impact of diet on the small intestinal metabolic niche, distinct spatial patterns suggest specific microbial influence on the metabolome in the small intestine. The here established map of intestinal metabolism and the newly identified metabolite-microbe associations provide a basis to connect spatial occurrence of bioactive compounds to host or microbe metabolism.