Amelioratory Role of Lactobacillus paracasei N1115 on Blood Glucose, Inflammation, Cognitive Function, and Gut Microbiota Composition in Type 2 Diabetes Mellitus Rats

This study aims to investigate the effect of probiotic Lactobacillus paracasei N1115 on Type 2 diabetes mellitus (T2DM) rats. SD rats were randomly divided into 5 groups, including control group (ND), diabetes mellitus (DM) group, and high (10(9) CFU/mL), medium (10(8) CFU/mL), or low (10(7) CFU/mL) doses of probiotics intervention groups. The ND rats were fed a normal diet, and the others were fed a high-fat diet and injected with streptozotocin (STZ) to build a T2DM model. In the three probiotic intervention groups, rats were given high, medium, or low doses of L. paracasei N1115 by gavage for 12 weeks. Results indicated that probiotics could prevent weight loss and decrease the blood glucose levels of T2DM rats, in a dose-dependent manner. A high dose of L. paracasei N1115 also led to a significant decline in the inflammatory response by regulating the TLR4/NF-kappa B inflammatory pathway and reducing proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and lipopolysaccharide (LPS) (p < 0.05). Besides, the memory factor cAMP and the cognitive regulatory pathway BDNF/TrkB were increased by high dose of L. paracasei N1115 treatment (p < 0.05), revealing an enhanced cognitive memory competence. In addition, analysis of the gut microbiome showed that a high dose of L.paracasei N1115 decreased Firmicutes/Bacteroidota ratio and increased the relative abundance of beneficial bacteria, such as unclassified_Lachnospiraceae, Ligilactobacillus, and Lachnospiraceae_NK4A136_group. The microbial gene contents associated with metabolic pathways, nicotinate and nicotinamide metabolism, glycine, serine, and threonine metabolism and the citrate cycle were upregulated under L. paracasei N1115 treatment. In summary, this study elucidated the regulatory effects of L. paracasei N1115 on T2DM in rats and revealed a promising dietary supplement for the treatment of T2DM.