Depletion of microbiome-derived molecules in the host using genetics.

The gut microbiota produce hundreds of molecules that are present at high concentrations in the host circulation. Unraveling the contribution of each molecule to host biology remains difficult. We developed a system for constructing clean deletions in spp., the source of many molecules from the gut microbiome. By applying this method to the model commensal organism , we knocked out genes for 10 -derived molecules that accumulate in host tissues. In mice colonized by a for which the production of branched short-chain fatty acids was knocked out, we discovered that these microbial products have immunoglobulin A-modulatory activity.