Engineered probiotics modulate the endocannabinoid system

Butyrate is a key microbial metabolite known to enhance host metabolic processes by reducing blood glucose levels and promoting energy metabolism, thereby potentially suppressing the risk of developing metabolic syndrome. In this study, we examined the activity of butyrate on modulating the endocannabinoid system, which regulates food intake and energy metabolism. Furthermore, we genetically engineered probiotics to produce butyrate to investigate their effects on the endocannabinoid system. Our study shows that the engineered probiotics exerted antagonistic effects on the endocannabinoid system by downregulating and upregulating the endocannabinoid-synthesizing and -degrading enzyme expression, respectively. Our results suggest that butyrate can modulate the endocannabinoid system, and incorporation of butyrate-producing bacteria into the gut microbiota can potentially aid in re-establishing homeostatic metabolic processes and alleviating metabolic syndrome.