Alterations in Microbiota and Metabolites Related to Spontaneous Diabetes and Pre-Diabetes in Rhesus Macaques

Spontaneous type 2 diabetes mellitus (T2DM) macaques are valuable resources for our understanding the pathological mechanism of T2DM. Based on one month’s fasting blood glucose survey, we identified seven spontaneous T2DM macaques and five impaired glucose regulation (IGR) macaques from 1408 captive individuals. FPG, HbA1c, FPI and IR values were significant higher in T2DM and IGR than in controls. 16S rRNA sequencing of fecal microbes showed the significantly greater abundance of Oribacterium, bacteria inhibiting the production of secondary bile acids, and Phascolarctobacterium, bacteria producing short-chain fatty acids was significantly lower in T2DM macaques. In addition, several opportunistic pathogens, such as Mogibacterium and Kocuria were significantly more abundant in both T2DM and IGR macaques. Fecal metabolites analysis based on UHPLC-MS identified 50 differential metabolites (DMs) between T2DM and controls, and 26 DMs between IGR and controls. The DMs were significantly enriched in the bile acids metabolism, fatty acids metabolism and amino acids metabolism pathways. Combining results from physiochemical parameters, microbiota and metabolomics, we demonstrate that the imbalance of gut microbial community leading to the dysfunction of glucose, bile acids, fatty acids and amino acids metabolism may contribute to the hyperglycaemia in macaques, and suggest several microbes and metabolites are potential biomarkers for T2DM and IGR macaques.