The bone marrow-gut axis: a bidirectional regulatory network in inflammation, graft-versus-host disease, and aging

The bone marrow (BM) and intestine are highly regenerative organ systems that coordinate hematopoietic and immune homeostasis. While the BM sustains lifelong blood production through hematopoietic stem cells (HSCs) within specialized niches, the intestine maintains barrier integrity and immune balance through intestinal stem cells (ISCs), epithelial cells, immune cells, and a complex microbial ecosystem. Increasing evidence supports bidirectional communication between these two organs under physiological and pathological conditions. However, current perspectives often emphasize microbiota-centered mechanisms and may not fully capture the integrated nature of BM–gut interactions. In this review, we synthesize current insights into the cellular and molecular crosstalk between BM and intestine in inflammation, graft-versus-host disease (GVHD), and aging. We discuss how barrier integrity, stem cell dynamics, immune signaling, and microbial factors collectively shape hematopoietic regulation. In addition, we evaluate emerging therapeutic strategies and clinical outcomes targeting the BM–gut axis, including BM-derived mesenchymal stromal cell (BM-MSC) transplantation and gut microbiota modulation. A deeper understanding of this axis may inform novel approaches to mitigate inflammatory injury, improve HSC transplantation outcomes, and promote healthy aging.