Introduction: Gut microbiota dysbiosis have been identified in renal transplantation, changes of microbial signature and metabolites maybe affect allograft rejection. The study aimed to provide a direct evidence and comprehensive understanding of microbiota dysbiosis in patients after renal transplantation, and provide a new strategy for clinical diagnosis and treatment.
Method: This study is descriptive and observational, carried out with patients from a single center in Tianjin First Central Hospital (Tianjin, China). A total of 36 participants were enrolled, comprising 17 patients diagnosed with rejection, 7 patients allograft dysfunction without rejection and 12 healthy control subjects. Metagenomic and untargeted metabolomic analyses of fecal samples and plasma samples were performed, then microbiota, metabolites and potential signaling pathways that might play important roles in outcome were screened out.
Results: First, the beta-diversity analysis based on Bray Curits distance showed that structure of gut microbiota among the 3 group was significantly diffeent (P < 0.001). Second, LEfSe analysis suggested that Ruminococcus increase, while Bacteroides and Enterocloster decrease were the essential characteristics in rejection group. Third, the functional annotations of the metagenome unveiled multiple significant pathway shifts of the gut microbiota in rejection group, such as phenylalanine, tyrosine and tryptophan biosynthesis, glycosaminoglycan degradation, fatty acid biosynthesis, biotin metabolism. Fourth, non-targeted fecal and serum metabolomics results showed that there were significant differences in metabolites among the three groups, such as histamine and stearic acid increased in the rejection group which aggravated immune response, while arachidonic acid decreased inhibited immune response. Finally, to further elucidate the relationship between gut microbiota and metabolites, we construct multi-omics biological correlation (MOBC) maps, which highlights fatty acid metabolism and amino acids biosynthesis and metabolism, with increased 4-Hydroxybenzoic acid and decreased spermidine.
Conclusions: This study showed specific gut microbiome and metabolome features in renal allograft rejection. These findings provide direct evidence for the correlation of gut microbiota dysbiosis and metabolites changes in allograft rejection, and also provide a potential strategy to further recognize rejection through gut microbiota dysbiosis related metabolite changes.