Production of deoxycholic acid by low-abundant microbial species is associated with impaired glucose metabolism.

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  • 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.
      (© 2024. The Author(s).)
    • References:
      Nat Med. 2022 Feb;28(2):303-314. (PMID: 35177860)
      Cell Metab. 2013 Feb 5;17(2):225-35. (PMID: 23395169)
      Metabolism. 2020 Feb;103:154042. (PMID: 31785259)
      J Lipid Res. 2012 Aug;53(8):1690-700. (PMID: 22645248)
      Diabetes. 2013 Dec;62(12):4184-91. (PMID: 23884887)
      PLoS One. 2018 Jul 30;13(7):e0200908. (PMID: 30059528)
      J Intern Med. 2015 Dec;278(6):645-59. (PMID: 26096600)
      Nat Rev Microbiol. 2021 Feb;19(2):77-94. (PMID: 32968241)
      Diabetes Metab J. 2019 Jun;43(3):257-272. (PMID: 31210034)
      Curr Opin Gastroenterol. 2014 May;30(3):332-8. (PMID: 24625896)
      FEBS Lett. 2018 Jun;592(12):2070-2082. (PMID: 29683480)
      Gut Microbes. 2021 Jan-Dec;13(1):1-20. (PMID: 33938389)
      Nature. 2015 Jan 8;517(7533):205-8. (PMID: 25337874)
      Nat Chem Biol. 2015 Sep;11(9):685-90. (PMID: 26192599)
      J Chromatogr B Biomed Sci Appl. 1998 Apr 24;708(1-2):21-6. (PMID: 9653942)
      Anaerobe. 2010 Apr;16(2):137-46. (PMID: 19464381)
      Gut Microbes. 2019;10(4):481-503. (PMID: 30589376)
      Lipids. 2006 Sep;41(9):835-43. (PMID: 17152920)
      J Lipid Res. 2006 Feb;47(2):241-59. (PMID: 16299351)
      Front Cell Infect Microbiol. 2016 Dec 20;6:191. (PMID: 28066726)
      Nature. 2020 Jun;582(7813):566-570. (PMID: 32555455)
      Science. 2015 Oct 2;350(6256):aac5992. (PMID: 26430127)
      Nature. 2023 Aug;620(7973):381-385. (PMID: 37532933)
      Gigascience. 2021 Feb 16;10(2):. (PMID: 33590861)
      Nat Methods. 2012 Mar 04;9(4):357-9. (PMID: 22388286)
      Microbiol Immunol. 1999;43(9):893-7. (PMID: 10553682)
      J Lipid Res. 1992 Apr;33(4):599-604. (PMID: 1527482)
      Cell Metab. 2020 Sep 1;32(3):379-390.e3. (PMID: 32652044)
      Gut Microbes. 2020 May 3;11(3):381-404. (PMID: 31177942)
      Toxicol Sci. 2011 Oct;123(2):359-67. (PMID: 21747115)
      Cell Metab. 2016 Jul 12;24(1):41-50. (PMID: 27320064)
      Cell Metab. 2015 Aug 4;22(2):228-38. (PMID: 26244932)
      Am J Physiol Gastrointest Liver Physiol. 2020 Mar 1;318(3):G554-G573. (PMID: 31984784)
      Nature. 2013 Jul 4;499(7456):97-101. (PMID: 23803760)
      J Lipid Res. 2020 Nov;61(11):1450-1463. (PMID: 32661017)
      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