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. 2021 Jul 7;11:692951. doi: 10.3389/fonc.2021.692951

Table 1.

Mechanisms by which the gut microbiota affects GVHD.

Influence of gut microbiota on GVHD Mechanisms References
Lactobacillus shows improvement in GVHD (86)
Disruption of gut microbiota diversity aggravates GVHD (86, 91, 93)
Butyrate, a metabolite of the gut microbiota, attenuates GVHD Butyrate improved IEC junctional integrity, decreased apoptosis (88, 89)
Lachnospiraceae is negatively associated with GVHD (9093)
Indole, a metabolite of the gut microbiota, improves GVHD Indole upregulates genes associated with IFN1 response, limits intestinal epithelial damage, reduces inflammatory cytokine production, and decreases GVHD pathology and GVHD mortality. (95)
GVHD progression was induced by TMAO, a circulating gut microbial metabolite TMAO enhances M1 macrophage polarization and establishes an environment for Th1 and Th17 responses (96)
Antibiotic use alters the composition of the gut microbiota and increases GVHD Loss of protective colonic mucosa and impairment of intestinal barrier function due to antibiotics (97)
Obesity aggravates GVHD by affecting the gut microbiota Obesity reduces the diversity of the gut microbiota and reduces Clostridiaceae abundance, leading to increased intestinal permeability, transintestinal transit of endotoxins, and radiation-induced gastrointestinal damage in mice (107)
The microbiota controls MHC-II at the pre-transplant IEC Microbiota depletion inhibits IL-12/23p40 production by ileal macrophages, IL-12/23p40 prevents upregulation of MHC class II cells on IECs and initiation of lethal GVHD in the gastrointestinal tract (108)
The gut microbiota metabolite sensor G-protein-coupled receptor 43 (GPR43) attenuates gastrointestinal GVHD GVHD protection by SCFAs requires GPR43-mediated ERK phosphorylation and activation of NLRP3 inflammasome in host non-hematopoietic target tissues (109)