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

Clostridial metabolite production The clostridia are Firmicute bacterial commensals commonly found in the mammalian gut. Clostridia produce a range of metabolites that diffuse into the host's circulation and have been difficult to manipulate genetically, but Guo et al. successfully developed a CRISPR-Cas9 deletion system in Clostridium sporogenes (see the Perspective by Henke and Clardy). The authors used deletion mutants and mass spectrometry to elucidate clostridial synthesis of several different branched short-chain fatty acids (SCFAs), including isobutyrate, 2-methylbutyrate, and isovalerate. Germ-free mice colonized with mutants incapable of synthesizing SCFAs showed altered immunoglobulin A production. This finding potentially links bacterial SCFA production and host responses to the presence of the clostridia. Science , this issue p. eaav1282 ; see also p. 1309