Fig. 2

Modulation mechanisms of the intestinal microbiota during GVHD and potential solutions of microbiota dysbiosis. A During allo-HSCT, conditioning regimens (including total body irradiation, chemotherapy and antibiotics) disrupt integrity of intestinal barrier. Intestinal bacteria and their metabolites translocate into the intestinal lamina propria to regulate the progression of aGVHD. Microbiota-associated molecular patterns can be recognized by the PPRs expressed on APCs, neutrophils and IECs, including TLRs and NLRs. APCs regulate the activation and expansion of donor T cells, including Treg, Th1 and Th17 cells. Neutrophils can aggravate aGVHD through impairing the intestinal tissues via reactive oxygen species. B cells in the intestinal lamina propria secrete soluble IgA to regulate the interactions between the host and microbiota, and development of B-cell lineage is influenced by the intestinal microbiota. Recipient MAIT cells mitigate aGVHD by maintaining intestinal barrier integrity and decreasing the proinflammatory donor Th1 and Th17 cells. MAIT cells also produce IL-17A to alleviate aGHVD. Indoles improve aGVHD via type I interferon response or activating AhRs on ILCs, which protect and repair the intestinal barrier from damage. SCFAs repair intestinal barrier integrity and inhibit IECs apoptosis, resulting in alleviating aGVHD. TMAO promotes the polarization of M1 macrophage which induces the activation of Th1 and Th17 cells, resulting in GVHD exacerbation. IEC, intestinal epithelial cell; ISC, intestinal stem cell; AMPs, antimicrobial peptides; SCFAs, short chain fatty acids; TMAO, trimethylamine N-oxide; ILC, innate lymphoid cell; MAIT, mucosal-associated invariant T cell; Th1, T helper 1 cell; Th17, T helper 17 cell; Treg, regulatory T cell; TLR, Toll-like receptor; NLRs, NOD-like receptors; AhR, aryl hydrocarbon receptor; GPR, G-protein-coupled receptor. B Interventions strategies modulating intestinal microbiota mainly include antibiotics, prebiotics, probiotics, postbiotics and FMT