Gut microbiota-bone marrow axis: how intestinal signals remodel hematopoiesis and immune status

Abstract

The gut microbiota, as a complex ecological system within the host, plays a critical role not only in regulating local intestinal immunity and metabolism but also in influencing hematopoietic stem cell (HSC) function and immune cell lineage differentiation through the gut-bone marrow axis. This review comprehensively examines how the gut microbiota remodels hematopoiesis and immune status via multiple mechanisms, particularly by modulating systemic inflammation, the bone marrow microenvironment, and HSC fate decisions. Special emphasis is placed on the role of Toll-like receptor (TLR) signaling pathways in linking the gut microbiota to bone metabolism and immune regulation. The review also integrates recent insights from single-cell sequencing technologies that reveal hematopoietic lineage biases in the bone marrow and explores the development and immune memory of gut-associated B cell populations during early life. By systematically synthesizing recent advances in the interaction between gut microbiota and bone marrow hematopoiesis, this article aims to provide a theoretical foundation for understanding how gut microbiota regulate systemic immune homeostasis and bone metabolism and to identify potential therapeutic targets for future interventions.