Cholesterol Metabolism by Uncultured Human Gut Bacteria Influences Host Cholesterol Level

Douglas J. Kenny, Damian R. Plichta, Dmitry Shungin, Nitzan Koppel, A. Brantley Hall, Beverly Fu, Ramachandran S. Vasan, Stanley Y. Shaw, Hera Vlamakis, Emily P. Balskus, Ramnik J. Xavier

Research output: Contribution to journalArticlepeer-review

145 Scopus citations


The human microbiome encodes extensive metabolic capabilities, but our understanding of the mechanisms linking gut microbes to human metabolism remains limited. Here, we focus on the conversion of cholesterol to the poorly absorbed sterol coprostanol by the gut microbiota to develop a framework for the identification of functional enzymes and microbes. By integrating paired metagenomics and metabolomics data from existing cohorts with biochemical knowledge and experimentation, we predict and validate a group of microbial cholesterol dehydrogenases that contribute to coprostanol formation. These enzymes are encoded by ismA genes in a clade of uncultured microorganisms, which are prevalent in geographically diverse human cohorts. Individuals harboring coprostanol-forming microbes have significantly lower fecal cholesterol levels and lower serum total cholesterol with effects comparable to those attributed to variations in lipid homeostasis genes. Thus, cholesterol metabolism by these microbes may play important roles in reducing intestinal and serum cholesterol concentrations, directly impacting human health.

Original languageEnglish (US)
Pages (from-to)245-257.e6
JournalCell Host and Microbe
Issue number2
StatePublished - Aug 12 2020
Externally publishedYes


  • Clostridium cluster IV
  • Framingham Heart Study
  • cholesterol
  • coprostanol
  • hydroxysteroid dehydrogenase
  • metabolomics
  • metagenomic species
  • metagenomics
  • microbial dark matter
  • microbiome

ASJC Scopus subject areas

  • Virology
  • Parasitology
  • Microbiology


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