Characterization of interactions of dietary cholesterol with the murine and human gut microbiome
Le HH, Lee MT, Besler KR, Comrie JMC, Johnson EL
Nature microbiology · 114 citations
How it was studied
- Design
- Animal study (classified by our AI screen)
- Studied in
- Animals
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Independent funding
- Government
- U.S. Department of Health and Human Services
- Nonprofit
- Canadian Institute for Advanced Research
- Government
- New York State Stem Cell Science
- Government
- National Institutes of Health
- Government
- National Institute of General Medical Sciences
- Government
- NIGMS NIH HHS
- Government
- NIH HHS
- Government
- U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences
- Grants
- National Institute of General Medical Sciences (R35 GM138281); National Institutes of Health (1s10od018516-01); National Institutes of Health (5r35gm138281-05); U.S. Department of Health and Human Services (R35GM138281)
Based on 8 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2022-08-18 · Nat Microbiol · vol. 7 · issue 9 · pp. 1390–1403
- Publisher
- Nature Portfolio
- Cited
- 129 citations · more than 99% of similar papers · 9.0× the field average
- Impact
- Top 10% most cited in its field
- References
- 94 works
- Access
- Open access (hybrid journal) · CC-BY
- Research areas
- Gut microbiota and health · Metabolomics and Mass Spectrometry Studies · Probiotics and Fermented Foods
- Keywords
- Microbiome, Biology, Bacteroides thetaiotaomicron, Bacteroides, Metagenomics, Cholesterol, Biochemistry, Genetics, Bacteria, Gene
- MeSH
- animals, humans, mice, bacteroides, cholesterol, sulfotransferases, dietary fats, cholesterol, dietary, microbiota, gastrointestinal microbiome
5 authors
From US
- Henry H. LeCornell University
- Min-Ting LeeCornell University
- Kevin R. BeslerCornell University
- Janine M. C. ComrieCornell University
- Elizabeth L. Johnson · correspondingCornell University
Abstract
Consumption of dietary lipids, such as cholesterol, modulates the gut microbiome with consequences for host health through the production of microbiome-derived metabolites. Despite the implications for host metabolism, a limited number of specific interactions of the gut microbiome with diet-derived lipids have been characterized. This is partially because obtaining species-level resolution of the responsible taxa can be challenging and additional approaches are needed to identify health-relevant metabolites produced from cholesterol-microbiome interactions. Here we performed bio-orthogonal labelling sort sequence spectrometry, a click chemistry based workflow, to profile cholesterol-specific host-microbe interactions. Mice were exposed to an alkyne-functionalized variant of cholesterol and 16S ribosomal RNA gene amplicon sequencing of faecal samples identified diet-derived cholesterol-interacting microbes from the genera Bacteroides, Bifidobacterium, Enterococcus and Parabacteroides. Shotgun metagenomic analysis provided species-level resolution of diet-derived cholesterol-interacting microbes with enrichment of bile acid-like and sulfotransferase-like activities. Using untargeted metabolomics, we identify that cholesterol is converted to cholesterol sulfate in a Bacteroides-specific manner via the enzyme BT_0416. Mice monocolonized with Bacteroides thetaiotaomicron lacking Bt_0416 showed altered host cholesterol and cholesterol sulfate compared with wild-type mice, identifying a previously uncharacterized microbiome-transformation of cholesterol and a mechanism for microbiome-dependent contributions to host phenotype. Moreover, identification of a cholesterol-responsive sulfotransferase in Bacteroides suggests diet-dependent mechanisms for altering microbiome-specific cholesterol metabolism. Overall, our work identifies numerous cholesterol-interacting microbes with implications for more precise microbiome-conscious regulation of host cholesterol homeostasis.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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