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Interaction of gut microbiota with bile acid metabolism and its influence on disease states

Abstract

Primary bile acids serve important roles in cholesterol metabolism, lipid digestion, host-microbe interactions, and regulatory pathways in the human host. While most bile acids are reabsorbed and recycled via enterohepatic cycling, ∼5% serve as substrates for bacterial biotransformation in the colon. Enzymes involved in various transformations have been characterized from cultured gut bacteria and reveal taxa-specific distribution. More recently, bioinformatic approaches have revealed greater diversity in isoforms of these enzymes, and the microbial species in which they are found. Thus, the functional roles played by the bile acid-transforming gut microbiota and the distribution of resulting secondary bile acids, in the bile acid pool, may be profoundly affected by microbial community structure and function. Bile acids and the composition of the bile acid pool have historically been hypothesized to be associated with several disease states, including recurrent Clostridium difficile infection, inflammatory bowel diseases, metabolic syndrome, and several cancers. Recently, however, emphasis has been placed on how microbial communities in the dysbiotic gut may alter the bile acid pool to potentially cause or mitigate disease onset. This review highlights the current understanding of the interactions between the gut microbial community, bile acid biotransformation, and disease states, and addresses future directions to better understand these complex associations.

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Acknowledgements

This work was supported by the NIH grant 1R21-AI114722-01 (MJS and AK), Minnesota’s Discovery, Research and InnoVation Economy grant from the University of Minnesota (MJS and AK), and the University of Minnesota Clinical and Translational Science Institute UL1TR000114 grant via the National Center for Advancing Translational Sciences of the NIH (ARW).

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Correspondence to Michael J. Sadowsky.

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Any studies with humans or animals performed by any of the authors were approved by the University of Minnesota Institutional Review Board (IRB) and Institutional Animal Care and Use Committee (IACUC). As is known by the authors, referenced studies adhere to applicable international, national, and/or institutional guidelines for the care and use of animals.

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Alexander Khoruts and Michael J. Sadowsky these authors contributed equally to this work.

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Staley, C., Weingarden, A.R., Khoruts, A. et al. Interaction of gut microbiota with bile acid metabolism and its influence on disease states. Appl Microbiol Biotechnol 101, 47–64 (2017). https://doi.org/10.1007/s00253-016-8006-6

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Keywords

  • Bile acids
  • Microbial metabolism
  • Host-interactions
  • Dysbiosis
  • C. difficile