Proteomics

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Gut Microbially Produced Bile Acid Metabolite Lengthens Circadian Period in Host Intestinal Cells

ABSTRACT: Although it has been shown that host health, circadian signaling, and the microbiome are tightly connected, the mechanistic links remain unclear. We identified a bile acid metabolite, lithocholic acid (LCA), as a circadian modulator by screening a focused library of gut microbial metabolites. Out of the larger class of compounds, LCA, and to a lesser extent isoLCA, uniquely lengthened the circadian period of hPer2 transcription in a dose-responsive manner in human colonic cells. LCA modulated the casein kinase 1 / (CK1/)-protein phosphatase 1 (PP1) feedback loop and stabilized core clock protein cryptochrome 2 (CRY2). Furthermore, we showed that LCA feeding alters circadian transcription in mouse colons. Thus, our work identifies LCA as an endogenous molecular link between host circadian biology and the microbiome, providing a new avenue to examine host health.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Colon

DISEASE(S): Colon Cancer

SUBMITTER: Robyn Eisert  

LAB HEAD: A. Sloan Devlin

PROVIDER: PXD060420 | Pride | 2026-05-25

REPOSITORIES: Pride

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8147_CP_Feb2024_phospho_Fr24_0000008260_psc20ppm_canonical.mzid Mzid
8149_CP_Feb2024_phospho_Fr23_0000008259_psc20ppm_canonical.mzid Mzid
8153_CP_Feb2024_phospho_Fr22_0000008258_psc20ppm_canonical.mzid Mzid
8157_CP_Feb2024_phospho_Fr21_0000008257_psc20ppm_canonical.mzid Mzid
8161_CP_Feb2024_phospho_Fr20_0000008256_psc20ppm_canonical.mzid Mzid
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Publications

Gut microbiome-produced bile acid metabolite lengthens the circadian period in host intestinal cells.

Powell Chelsea E CE   McSween Alana M AM   Dohnalová Lenka L   Kim Cecilia H CH   Eisert Robyn J RJ   Sun Zhen-Yu J ZJ   Seo Hyuk-Soo HS   Marquardt Vincent V   Dhe-Paganon Sirano S   Thaiss Christoph A CA   Devlin A Sloan AS  

Proceedings of the National Academy of Sciences of the United States of America 20260311 11

Host circadian signaling, feeding, and the gut microbiome are tightly interconnected. Changes in the gut microbial community can affect the expression of core clock genes, but the specific metabolites and molecular mechanisms that mediate this relationship remain largely unknown. Here, we sought to identify gut microbial metabolites that impact circadian signaling. Through a phenotypic screen of a focused library of gut microbial metabolites, we identified a bile acid metabolite, lithocholic aci  ...[more]

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