Fig. 9

A simplified schematic diagram illustrating the dysregulated gut microbiota and bile acid metabolism positive feedback loop, which exacerbates immune responses and exacerbates aGVHD. Improper treatment of patients undergoing allo-HSCT alters the gut microbiota and disrupts the imbalanced bile acid metabolism. Dysregulated bile acid metabolism results in reduced production of IL1RN, defensins, and resistin. Deficiency of defensins and resistin fails to inhibit harmful microorganisms, leading to increased production of proinflammatory cytokines and proteins, such as IL-17A, IL-1β, TNFα, IL-6, IL-12, and members of the S100A family. Additionally, it was determined that resistin can inhibit aGVHD by downregulating the expression of IL1B, DUSP1, and members of the AP-1 family