Metabolomics identifies the intestinal geography of microbial metabolite production

We determined the metabolome and microbial composition in healthy colonized and germ-free mice. The resulting anatomically-resolved maps of 128 metabolites in 15 intestinal sites revealed luminal contents and mucus of small and large intestine as the four metabolically most distinct niches, with a general shift from higher concentrations of amino acids in the small intestine, to organic acids, vitamins, and nucleotides in the large intestine. More subtle metabolomic differences were found within niches of the inherently difficult to access small intestine, where spatial patterns provided evidence for microbial conversion of metabolites, for example purines to allantoin in its distal section or creatine formation in the mucus of the jejunum. Microbial indole metabolism regulating the release of intestinal hormones that control host digestion was unexpectedly found to occur in both the large and the small intestines. Specific microbes were identified as potential producers for about half of the 35 metabolites of microbial origin. For two metabolites with the largest relative concentration change in colonized versus germ-free mice, the short chain fatty acid butyrate and the bile acid chenodeoxycholate, we identified Lachnospiraceae as responsible microbes.

Link to the paper in external page "Nature Metabolism".