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

Science. 2019 Dec 13;366(6471):eaav1282. doi: 10.1126/science.aav1282.


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 Clostridium spp., the source of many molecules from the gut microbiome. By applying this method to the model commensal organism Clostridium sporogenes, we knocked out genes for 10 C. sporogenes-derived molecules that accumulate in host tissues. In mice colonized by a C. sporogenes for which the production of branched short-chain fatty acids was knocked out, we discovered that these microbial products have immunoglobulin A-modulatory activity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • CRISPR-Associated Protein 9
  • CRISPR-Cas Systems
  • Clostridium / genetics*
  • Clostridium / metabolism*
  • Gastrointestinal Microbiome / genetics*
  • Gene Deletion
  • Gene Editing / methods*
  • Host Microbial Interactions*
  • Metabolic Networks and Pathways / genetics*
  • Mice
  • Mice, Inbred Strains


  • CRISPR-Associated Protein 9

Supplementary concepts

  • Clostridium sporogenes