Exploration of the hypoglycemic effect and mechanism of Lactobacillus plantarum LH36 on type 2 diabetic mice through intestinal flora and non-targeted metabolomics

As a common probiotic, Lactobacillus plantarum has a unique probiotic potential in improving metabolic diseases, but its protective effects and specific mechanism on type 2 diabetes (T2D) are still unclear. This study systematically evaluated the alleviating effect of L. plantarum LH36 on the T2D mice model induced by high-fat diet (HFD) combined with streptozotocin (STZ) through blood physiological indexes, histopathological changes, intestinal flora and non-targeted metabolomics analysis. The results showed that after oral administration of L. plantarum LH36, the loss of body weight, blood glucose regulation capacity and insulin resistance of T2D mice were significantly improved. The histopathological damages to the colon and liver were also effectively alleviated. In addition, the intestinal flora sequencing results showed that L. plantarum LH36 treatment reversed the structural disorder of intestinal flora induced by HFD + STZ, improved the richness, diversity and evenness of the intestinal flora, including Chao1, Shannon, and Simpson indices. Specifically, Bacteroidetes was increased but Firmicutes was decreased at the phylum level. The disorders of Lactobacillus and Butyrobacter were restored at the genus level. In addition, non-targeted metabolomics results further confirmed that L. plantarum LH36 treatment could significantly restore the metabolic disorder in T2D mice and regulate multiple metabolites with diverse functions, including various long-chain acylcarnitine, diacylglycerols and pentadecanic acid, etc. These results verified that L . plantarum LH36 treatment exerted hypoglycemic effects by improving insulin resistance, reducing blood lipids, alleviating pathological changes in the colon and liver, as well as adjusting the intestinal flora disorders and regulating the host's metabolic profiles. These results offer crucial scientific support for developing L. plantarum as a promising adjunct therapeutic approach for T2D.