Diet, obesity, and the gut microbiome as determinants modulating metabolic outcomes in a non-human primate model

ABSTRACT: BACKGROUND: The objective of this study was to increase understanding of the complex interactions between diet, obesity, and the gut microbiome of adult female non-human primates (NHPs). Subjects consumed either a Western (n=15) or Mediterranean (n=14) diet designed to represent human dietary patterns for 31 months. Body composition was determined using CT, fecal samples were collected, and shotgun metagenomic sequencing was performed. Gut microbiome results were grouped by diet and adiposity. RESULTS: Diet was the main contributor to gut microbiome bacterial diversity. Adiposity within each diet was associated with subtle shifts in the proportional abundance of several taxa. Mediterranean diet-fed NHPs with lower body fat had a greater proportion of Lactobacillus animalis than their higher body fat counterparts. Higher body fat Western diet-fed NHPs had more Ruminococcus champaneliensis and less Bacteroides uniformis than their low body fat counterparts. Western diet-fed NHPs had significantly higher levels of Prevotella copri than Mediterranean diet NHPs. Western diet-fed subjects were stratified by P. copri abundance (P. copri(HIGH) versus P. copri(LOW)), which was not associated with adiposity. Overall, Western diet-fed animals in the P. copri(HIGH) group showed greater proportional abundance of B. ovatus, B. faecis, P. stercorea, P. brevis, and Faecalibacterium prausnitzii than those in the Western P. copri(LOW) group. Western diet P. copri(LOW) subjects had a greater proportion of Eubacterium siraeum. E. siraeum negatively correlated with P. copri proportional abundance regardless of dietary consumption. In the Western diet group, Shannon diversity was significantly higher in P. copri(LOW) when compared to P. copri(HIGH) subjects. Furthermore, gut E. siraeum abundance positively correlated with HDL plasma cholesterol indicating that those in the P. copri(LOW) population may represent a more metabolically healthy population. Untargeted metabolomics on urine and plasma from Western diet-fed P. copri(HIGH) and P. copri(LOW) subjects suggest early kidney dysfunction in Western diet-fed P. copri(HIGH) subjects. CONCLUSIONS: In summary, the data indicate diet to be the major influencer of gut bacterial diversity. However, diet and adiposity must be considered together when analyzing changes in abundance of specific bacterial taxa. Interestingly, P. copri appears to mediate metabolic dysfunction in Western diet-fed NHPs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40168-021-01069-y.