Tyrosine Supplement Ameliorates Murine aGVHD by Modulation of Gut Microbiome and Metabolome

Abstract Background The microbial communities and their metabolic components in gut are essential for immune homeostasis and profoundly influence the host susceptibility to many immune-mediated diseases including acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the functional connections between microbiome and metabolites in aGVHD are poorly understood because of the complexity of gastrointestinal environment. Thus, we initially performed 16S ribosomal DNA gene sequencing and ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS)-based metabolomics to unleash the gut microbiota and fecal metabolic phenotype in aGVHD murine model. Results A Lachnospiraceae_unclassified was significantly downregulated while the relative abundance of Clostridium XI, Clostridium XIVa and Enterococcus were increased in aGVHD happened group. Meanwhile, a lower content of tyrosine was observed in the gut of aGVHD mice. The correlation analysis revealed that tyrosine-related metabolites inversely correlated with Clostridium XIVa, Blautia and Enterococcus in aGVHD condition. In addition to explore the importance and function of tyrosine, we supplied different tyrosine content diets to mice during transplantation. Additional tyrosine supplements could improve overall survival, ameliorate symptoms at the early stage of aGVHD and changed the structure and composition of gut microbiota and fecal metabolic phenotype, while mice with aGVHD deprived from tyrosine displayed worse manifestations than vehicle. Conclusions Overall, a better understanding of the roles of gut microbiota-metabolomes interconnectedness in aGVHD could help identify disease biomarkers and offer better targets for diagnosis and treatment.