Production of deoxycholic acid by low-abundant microbial species is associated with impaired glucose metabolism
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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.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 4276 |
| Tidsskrift | Nature Communications |
| Vol/bind | 15 |
| Antal sider | 11 |
| ISSN | 2041-1723 |
| DOI | |
| Status | Udgivet - 2024 |
Bibliografisk note
Funding Information:
Stanford University and the Chan Zuckerberg Biohub have patents pending for microbiome technologies on which A.B. and M.A.F. are co-inventors. M.A.F. is a co-founder and director of Federation Bio and Kelonia, a co-founder of Revolution Medicines, and a member of the scientific advisory boards of NGM Bio and Zymergen. S.L.H. reports having received royalty payments for inventions or discoveries related to cardiovascular diagnostics or therapeutics from Cleveland Heart Lab, a fully owned subsidiary of Quest Diagnostics, and Procter & Gamble, being a paid consultant for Zehna Therapeutics, and having received research funds from Procter & Gamble, Pfizer Inc., Roche Diagnostics and Zehna Therapeutics. F.B. is co-founder and shareholder of Roxbiosens Inc and Implexion Pharma AB, receives research funding from Biogaia AB, and a member of the scientific advisory board of Bactolife A/S. The remaining authors declare no competing interests.
Funding Information:
We thank Anna Hall\u00E9n, Carina Arvidsson, and Louise Helld\u00E9n for technical assistance and the Adam Arkin Lab for providing Eubacterium rectale ATCC 33656. This work was supported by grants from the Leducq Foundation (17CVD01), the Swedish Heart Lung Foundation (20210366), the Knut and Alice Wallenberg Foundation (2017.0026), the Swedish Research Council (2019-01599), AFA insurances (160337), the Novo Nordisk Foundation (NNF21OC0070298), and from the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALFGBG-718101). F.B. is a Torsten S\u00F6derberg Professor in Medicine and Wallenberg Scholar. S.L.H. and M.A.F. were also partially supported by National Institutes of Health grant P01 HL147823.
Publisher Copyright:
© The Author(s) 2024.
ID: 393272553