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• W4293067895 endingPage "1403" @default.
• W4293067895 startingPage "1390" @default.
• W4293067895 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." @default.
• W4293067895 created "2022-08-26" @default.
• W4293067895 creator A5006819710 @default.
• W4293067895 creator A5012253562 @default.
• W4293067895 creator A5018231918 @default.
• W4293067895 creator A5032804159 @default.
• W4293067895 creator A5065515784 @default.
• W4293067895 date "2022-08-18" @default.
• W4293067895 modified "2023-10-14" @default.
• W4293067895 title "Characterization of interactions of dietary cholesterol with the murine and human gut microbiome" @default.
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