Characteristics of the Serum Microbiota and Circulating Metabolites in Cynomolgus Monkeys With Spontaneous Type 2 Diabetes Mellitus

Background: Type 2 diabetes mellitus (T2DM) is widely recognized as a serious global public health concern with a substantial economic burden on patients, their families, and society. Accumulating evidence suggests that an etiologic role for serum microbiota and circulating metabolites in the pathogenesis of T2DM. This study aims to characterize the serum microbiota and circulating metabolites in cynomolgus monkeys with spontaneous T2DM, and provide a reference for the diagnosis and treatment of clinical T2DM. Methods: We collected serum samples of the 14 cynomolgus monkeys (15-20 years old, male) for serum microbiota analysis by 16S rRNA gene V3-V4 region amplicon sequencing and circulating metabolites analysis by ultra-high-performance liquid chromatography-tandem mass spectrometry, of which seven were spontaneous T2DM cynomolgus monkeys and seven were healthy controls. Results: Our results showed that the serum microbiota abundance and diversity were significantly increased in cynomolgus monkeys with spontaneous T2DM compared to healthy controls, the phyla of Cyanobacteria and Chloroflexi and the genera of Lactobacillus, rhodobacter and collinsella were also significantly increased. A total of 114 serum differentially expressed metabolites (DEMs) were identified, of which 22 were selected as potential biomarkers candidates related to spontaneous T2DM in cynomolgus monkeys by multivariate data analysis. In addition, serum levels of total SCFAs, acetate, butyrate, caproate, isobutyrate, and isovalerate were also significantly increased in the present study. The correlation network analyses have selected certain key DEMs, such as D-Psicose, 4-Oxoproline, D-Glutamine, and Hydroxyphenyllactic acid, which may serve as potential biomarkers for distinguishing between T2DM and healthy controls. Conclusion: Our results provide preliminary insights on perturbed serum microbiota and circulating metabolites of cynomolgus monkeys with spontaneous T2DM. These findings would be useful to develop microbiota-based strategies for T2DM prevention and control.