Calorie restriction ameliorates hyperglycemia, modulates the disordered gut microbiota, and mitigates metabolic endotoxemia and inflammation in type 2 diabetic rats

Purpose The effects of calorie restriction (CR) on gut microbiota and the mechanism of CR ameliorating hyperglycemia in streptozotocin (STZ)-induced T2DM model rats were explored. Methods High-fat diet and STZ injection were applied to induce T2DM model rats. Rats were divided into the following three groups: the control-diet ad libitum group, the T2DM model group fed with ad libitum diet, and the T2DM group fed with 30% restriction diet. 16S rRNA sequencing was used to determine the bacterial communities. Lipopolysaccharide (LPS)-binding protein (LBP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) were measured. Results Glucose tolerance and insulin sensitivity were improved by CR, as well as the levels of fasting and random plasma glucose. Besides, CR not only modulated the overall structure of gut microbiota but also had selective enrichment in anti-inflammatory bacteria such as Lachnospiraceae_NK4A136_group, Ruminococcaceae_9, Allobaculum, Alistipes, and Oscillibacter, and decreased pro-inflammatory pathogenic bacteria such as Bacteroides, Lachnoclostridium, and Bifidobacterium. Tax4Fun indicated that CR could regulate related functional pathways such as lipopolysaccharide biosynthesis, and the plasma levels of LBP, IL-6, and TNF-alpha were markedly reduced by CR, suggesting the mechanism of CR ameliorating hyperglycemia may associate with the modulation of disordered gut microbiota and the reduction of metabolic endotoxemia and inflammation. Conclusion CR could ameliorate hyperglycemia, the mechanism of which may associate with the alteration of the overall structure of gut microbiota, restoration of disordered microbiota function, and the downregulation of metabolic endotoxemia and inflammation in diabetic rats.