Host genetics and diet composition interact to modulate gut microbiota and predisposition to metabolic syndrome in spontaneously hypertensive stroke-prone rats

Metabolic syndrome encompasses obesity, glucose intolerance, hypertension and dyslipidemia, and is a global health concern; however, the interactions between diet and host physiology that predispose to metabolic syndrome are incompletely understood. To understand these interactions, we explored the effects of high-fat diet (HFD; 33% fat) on energy balance, gut microbiota and key risk factors of metabolic syndrome in spontaneously hypertensive stroke-prone (SHRSP) and Wistar-Kyoto (WKY) rats. We found that SHRSP rats were hypertensive, hyperphagic, less sensitive to the hypophagic effects of exendin-4, and expended more energy with diminished sensitivity to sympathetic blockade, compared to WKY rats. Notably, key thermogenic WKY rats. Whilst HFD promoted weight gain, adiposity, glucose intolerance, hypertriglyceridemia, hepatic lipidosis and increased plasma leptin in both SHRSP and WKY, the SHRSP weighed less but had comparable percent adiposity as WKY. Importantly, despite distinct differences in gut microbiota composition between the strains, diet had a preponderant impact on gut flora with some of the taxa being strongly associated with key metabolic parameters. Together, we provide evidence that interactions between host genetics and diet modulate gut microbiota and predispose SHRSP rats to develop metabolic syndrome.