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Production of deoxycholic acid by low-abundant microbial species is associated with impaired glucose metabolism.
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- Author(s): Wahlström A;Wahlström A; Brumbaugh A; Brumbaugh A; Brumbaugh A; Brumbaugh A; Brumbaugh A; Sjöland W; Sjöland W; Olsson L; Olsson L; Wu H; Wu H; Henricsson M; Henricsson M; Lundqvist A; Lundqvist A; Makki K; Makki K; Hazen SL; Hazen SL; Hazen SL; Hazen SL; Bergström G; Bergström G; Bergström G; Marschall HU; Marschall HU; Fischbach MA; Fischbach MA; Fischbach MA; Fischbach MA; Fischbach MA; Bäckhed F; Bäckhed F; Bäckhed F; Bäckhed F
- Source:
Nature communications [Nat Commun] 2024 May 20; Vol. 15 (1), pp. 4276. Date of Electronic Publication: 2024 May 20.- Publication Type:
Journal Article- Language:
English - Source:
- Additional Information
- Source: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
- Publication Information: Original Publication: [London] : Nature Pub. Group
- Subject Terms: Deoxycholic Acid*/metabolism ; Gastrointestinal Microbiome*/physiology ; Glucose*/metabolism ; Diabetes Mellitus, Type 2*/microbiology ; Diabetes Mellitus, Type 2*/metabolism; Animals ; Female ; Mice ; Humans ; Mice, Inbred C57BL ; Clostridium/metabolism ; Clostridium/genetics ; Cholic Acid/metabolism ; Male
- Abstract: Alterations in gut microbiota composition are suggested to contribute to cardiometabolic diseases, in part by producing bioactive molecules. Some of the metabolites are produced by very low abundant bacterial taxa, which largely have been neglected due to limits of detection. However, the concentration of microbially produced metabolites from these taxa can still reach high levels and have substantial impact on host physiology. To explore this concept, we focused on the generation of secondary bile acids by 7α-dehydroxylating bacteria and demonstrated that addition of a very low abundant bacteria to a community can change the metabolic output dramatically. We show that Clostridium scindens converts cholic acid into the secondary bile acid deoxycholic acid (DCA) very efficiently even though the abundance of C. scindens is low, but still detectable by digital droplet PCR. We also show that colonization of germ-free female mice with a community containing C. scindens induces DCA production and affects host metabolism. Finally, we show that DCA correlates with impaired glucose metabolism and a worsened lipid profile in individuals with type 2 diabetes, which implies that this metabolic pathway may contribute to the development of cardiometabolic disease.
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J Hepatol. 2000 Jan;32(1):4-10. (PMID: 10673060) - Grant Information: NNF21OC0070298 Novo Nordisk Fonden (Novo Nordisk Foundation); 17CVD01 Fondation Leducq; P01 HL147823 United States HL NHLBI NIH HHS; 160337 AFA Försäkring (AFA Insurance Foundation); 2017.0026 Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation); 20210366 Hjärt-Lungfonden (Swedish Heart-Lung Foundation); 2019-01599 Vetenskapsrådet (Swedish Research Council)
- Publication Date: Date Created: 20240520 Date Completed: 20240520 Latest Revision: 20240523
- Publication Date: 20240523
- Accession Number: PMC11106306
- Accession Number: 10.1038/s41467-024-48543-3
- Accession Number: 38769296
- Source:
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