Abstract:
: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.
journal_name
Cell Host Microbejournal_title
Cell host & microbeauthors
Kenny DJ,Plichta DR,Shungin D,Koppel N,Hall AB,Fu B,Vasan RS,Shaw SY,Vlamakis H,Balskus EP,Xavier RJdoi
10.1016/j.chom.2020.05.013subject
Has Abstractpub_date
2020-08-12 00:00:00pages
245-257.e6issue
2eissn
1931-3128issn
1934-6069pii
S1931-3128(20)30295-Xjournal_volume
28pub_type
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