The changing metabolic landscape of bile acids - keys to metabolism and immune regulation.

Celeste Allaband, Pieter C Dorrestein, Rob Knight, Ipsita Mohanty, Helena Mannochio-Russo, Yasin El Abiead, Lee R Hagey

Journal: Nature reviews. Gastroenterology & hepatology 2024;21(7):493-516

PMID: 38575682

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Abstract

Bile acids regulate nutrient absorption and mitochondrial function, they establish and maintain gut microbial community composition and mediate inflammation, and they serve as signalling molecules that regulate appetite and energy homeostasis. The observation that there are hundreds of bile acids, especially many amidated bile acids, necessitates a revision of many of the classical descriptions of bile acids and bile acid enzyme functions. For example, bile salt hydrolases also have transferase activity. There are now hundreds of known modifications to bile acids and thousands of bile acid-associated genes, especially when including the microbiome, distributed throughout the human body (for example, there are >2,400 bile salt hydrolases alone). The fact that so much of our genetic and small-molecule repertoire, in both amount and diversity, is dedicated to bile acid function highlights the centrality of bile acids as key regulators of metabolism and immune homeostasis, which is, in large part, communicated via the gut microbiome.

Address: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.; Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA, USA.; Department of Medicine, University of California San Diego, San Diego, CA, USA.; Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA, USA.; Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA.; Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA.; Department of Bioengineering, University of California San Diego, La Jolla, CA, USA.; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA. [email protected].; Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA. [email protected].; Department of Pharmacology, University of California San Diego, La Jolla, CA, USA. [email protected].; Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA. [email protected].

DOI: 10.1038/s41575-024-00914-3

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MeSH Terms: Bile Acids and Salts, Humans, Gastrointestinal Microbiome, Homeostasis