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dc.contributor.advisorBalskus, Emily P
dc.contributor.advisorXavier, Ramnik J
dc.contributor.authorKenny, Douglas J
dc.date.accessioned2021-08-04T05:02:36Z
dash.embargo.terms2022-11-23
dc.date.created2020
dc.date.issued2020-11-23
dc.date.submitted2020-11
dc.identifier.citationKenny, Douglas J. 2020. Cholesterol Metabolism by the Human Gut Microbiota. Doctoral dissertation, Harvard University Graduate School of Arts and Sciences.
dc.identifier.other28150986
dc.identifier.urihttps://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37368967*
dc.description.abstractThe 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.
dc.format.mimetypeapplication/pdf
dc.language.isoen
dash.licenseLAA
dc.subjectCholesterol
dc.subjectCoprostanol
dc.subjectEubacterium
dc.subjectHydroxysteroid dehydrogenase
dc.subjectMetagenomics
dc.subjectMicrobiota
dc.subjectMicrobiology
dc.subjectBiochemistry
dc.subjectChemistry
dc.titleCholesterol Metabolism by the Human Gut Microbiota
dc.typeThesis or Dissertation
dash.depositing.authorKenny, Douglas J
dash.embargo.until2022-11-23
dc.date.available2021-08-04T05:02:36Z
thesis.degree.date2020
thesis.degree.grantorHarvard University Graduate School of Arts and Sciences
thesis.degree.levelDoctoral
thesis.degree.namePh.D.
dc.contributor.committeeMemberSchreiber, Stuart L
dc.contributor.committeeMemberComstock, Laurie
dc.contributor.committeeMemberAlm, Eric
dc.type.materialtext
thesis.degree.departmentChemical Biology
dc.identifier.orcid0000-0002-2672-5507
dash.author.emaildkenny@g.harvard.edu


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