Gut Microbiota Composition Correlates to Trunk Fat Percentage in Male Cynomolgus Macaque Monkeys

Obesity and its co-morbidities are increasing as public health challenges worldwide. Non-human primates with their similarity to human physiology and susceptibility to metabolic diseases represent a valuable, clinically translational animal model in metabolic disease research. We aimed to characterize the impact of long-term high fat, high carbohydrate and high cholesterol diet (FFC) feeding on the host metabolism and gut microbiota in male Cynomolgus Macaque monkeys. Twenty-three male Cynomolgus Macaque (Macaca fascicularis) monkeys were housed indoors from the age of approximately 2 years and fed a FFC diet for 4.5 years. Diabetes and obesity-related parameters, gut microbiota composition, circulating bile acids and short chain fatty acids were characterized. The FFC diet induced obesity with elevated levels of trunk fat (TF%) of 39.7% ± 14.9%. There was a significant association between TF% and fasting insulin, HbA1c%, triglyceride levels, and the ratio of glycine- to taurine-conjugated bile acids. TF% was associated with changes in the fecal microbiota composition, predominantly driven by Coprococcus spp. and members of the families Enterobacteriaceae and Lactobacillaceae, similar to observations in humans with obesity. It is concluded that the FFC diet induced obesity, hypertriglyceridemia, impaired insulin sensitivity and dysregulated glucose metabolism. Microbial diversity did not differ between obesity states described as four TF% quartiles, but the fecal microbiota composition was significantly associated with the TF% driven by Coprococcus spp. and members of the families Enterobacteriaceae and Lactobacillaceae. Whether the gut microbiota changes were a cause or consequence of the obese state and impaired glucose metabolism remains to be studied.