Positive interactions among Corynebacterium glutamicum and keystone bacteria producing SCFAs benefited T2D mice to rebuild gut eubiosis

Abstract

Accumulating evidences strongly support the correlations between the compositions of gut microbiome and therapeutic effects on Type 2 diabetes (T2D). Notably, gut microbes such as Akkermansia muciniphila are found able to regulate microecological balance and alleviate dysmetabolism of mice bearing T2D. In order to search out similarly functional bacteria, bacteriophage MS2 with a good specificity to bacteria carrying fertility (F) factor were used to treat T2D mice. Based on multi-omics analysis of microbiome and global metabolism of mice, we observed that gavage of bacteriophage MS2 and metformin led to a significant increase in the abundance of Corynebacterium glutamicum and A. muciniphila, respectively. Consequently, the gut microbiota were remodeled, leading to variations in metabolites and a substantial increase in short-chain fatty acids (SCFAs). In which, the amount of acetate, propionate, and butyrate presented negative correlations to that of proinflammatory cytokines, which was beneficial to repairing the intestinal barriers and improving their functions. Moreover, main short fatty acid (SCFA) producers exhibited positive interactions, further facilitating the restoration of gut eubiosis. These findings revealed that C. glutamicum and its metabolites may be potential dietary supplements for the treatment of T2D. Moreover, our research contributes to a novel understanding of the underlying mechanism by which functional foods exert their anti-diabetic effects.

Keywords: Akkermansia muciniphila; Corynebacterium glutamicum; SCFAs; T2D; phage MS2.