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

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. Bile acids have important roles in human metabolism and immune regulation. In this Perspective, Dorrestein and colleagues discuss the technologies and data science-related approaches that are improving our understanding of the diversity of bile acids and their multifaceted roles.