Mucosal Immunol. 2025 Dec 21:S1933-0219(25)00137-0. doi: 10.1016/j.mucimm.2025.12.001. Online ahead of print.

ABSTRACT

The intestine and liver are physically interconnected through the biliary system, portal circulation, lymphatic network, and neural pathways, collectively forming the gut-liver axis. The gut-liver axis and the immune system are engaged in a complex regulatory relationship. Over the past few decades, significant progress has been made in elucidating how liver-derived bile acids (BAs) shape intestinal immunity through interactions with the gut microbiota. However, the multidirectional regulatory pathways by which the liver orchestrates intestinal immune homeostasis remain incompletely defined. In this review, we highlight liver-derived cues-including the BAs, neural signals, nutrient metabolism, hormones, hepatically secreted proteins, and the complement system-and their impact on intestinal innate and adaptive immune cells. Furthermore, we discuss how intestinal dysbiosis contributes to the progression of liver inflammation and hepatocellular carcinoma (HCC) via immune cells. A comprehensive understanding of these intricate interactions may uncover novel therapeutic strategies for treating gut- and liver-associated immune disorders.

PMID:41435890 | DOI:10.1016/j.mucimm.2025.12.001