Bile acids mediate liver-bone marrow crosstalk

Abstract

The modern dietary exposome is calorie dense and poor in nutritional quality resulting in a high prevalence of fatty liver disease and an increasing incidence of cardiometabolic disease and cancer. We investigated the impact of dietary composition on the interaction between the liver and haematopoietic systems in mice. Using xenograft and chemical-induced liver cancer models, we find that liver tumours per se have a minimal impact on haematopoietic stem and progenitor cell (HSPC) responses. In contrast, alterations in dietary composition had profound effects on the liver-bone marrow axis. Specifically, exposure to sucrose with or without dietary cholesterol had minimal impact on the HSPC response, while perturbations in bile acid biosynthesis synergises with dietary cholesterol to enhance HSPC responses. Pharmacological restoration of bile acid biosynthesis partially reversed these effects. We conclude that the crosstalk between the liver and bone marrow, and subsequent HSPC responses is regulated by bile acid biosynthesis.