Daniele Vitale, Mahmoud Karimi Azardaryany, Ghazal Alipour Talesh, Mahsa Shahidi, Vikki Ho, Suat Dervish, FX Himawan Haryanto Jong, Maito Suoh, Jacob George, Saeed Esmaili
Disruption of liver metabolism alters immune responses, with maximal immune activation occurring when metabolic stress increases bone marrow hematopoietic stem cell (HSC) activity. We previously showed that sustained HSC activation enhances liver immune surveillance and reduces tumor burden. In the present study, we show that short-term HSC stimulation alone is insufficient for tumor control. Dietary supplementation with cholesterol and cholic acid, however, synergistically stimulates HSC responses and markedly elevates serum taurocholic acid (T-CA). Pharmacological inhibition of the apical sodium-dependent bile acid transporter (ASBT) restores bile acid homeostasis and lowers circulating T-CA, attenuating HSC activation and liver inflammation. Collectively, these findings reveal a bile acid-mediated liver-bone marrow crosstalk with direct implications for metabolic and neoplastic liver diseases.