Bile Acids and Healthy Ageing

Bile acids (BAs) comprise a class of evolutionary-conserved cholesterol metabolites that are synthesized exclusively in the liver, circulate between the liver and intestine in the so-called enterohepatic circulation, and whose structures can extensively be modulated through the actions of gut bacterial enzymes. In the past decades, it has become clear that, in addition to their classical roles in intestinal fat absorption, bile formation, and cholesterol turnover, BAs also exert hormone-like functions via activation of nuclear and membrane-bound receptors that are expressed in a variety of cell types and modulate metabolic as well as immune functions. Particularly, microbiome-derived secondary BAs have emerged as important signaling molecules with broad impact. As the gut microbiome is amendable to compositional and functional modulation, the gut–liver axis may provide opportunities for novel strategies to promote healthy ageing, such as, to prolong healthspan, in the globally ageing population. This review aims to provide an overview of available literature linking BAs to (healthy) ageing. For this purpose, it contains a general overview of BA metabolism and the importance of the gut microbiome in the modulation of BA structure and function. Additionally, it provides a comprehensive review of the current knowledge on how (microbiome-derived) BAs are associated with health and lifespan and on the mechanisms by which BAs could modulate age-related disease in specified tissues.