Murine gut microbial interactions exert anti-hyperglycemic effects

Abstract

The correlations between gut microbiota and host metabolism had been studied extensively, whereas little relevant work had been done to investigate the impact of gut microbial interactions on host metabolism. Assisted with bacteriocin-targeting strategy, we aimed to identify the glucose and lipid metabolism-associated gut microbes by adjusting the gut microbial composition of high-fat diet-fed mice. To fulfill this goal, the Listeria monocytogenes-derived bacteriocin Lmo2776 secretion module was constructed and integrated into the genome of Escherichia coli Nissle 1917, yielding the Lmo2776-secreting strain EcN-2776. EcN-2776 administration decreased the blood glucose and increased the serum triglyceride of high-fat diet-fed mice. 16S rRNA gene amplicon sequencing indicated that intestinal secretion of Lmo2776 adjusted the gut microbial composition of high-fat diet-fed mice. Specifically, Lmo2776 restricted the growth of Ligilactobacillus murinus, thus alleviating its inhibitory impact towards Faecalibaculum rodentium. Further analyses indicated that Faecalibaculum rodentium administration decreased the fasting blood glucose of high-fat diet-fed mice, which might be achieved by the intestinal consumption of glucose by Faecalibaculum rodentium. Our study identified the glucose metabolism-associated gut microbes, uncovered their interactions, deciphered the impact of gut microbial interaction on host glucose metabolism, and paved the way for treating hyperglycemia from the perspective of gut microbial interactions.