Lactobacillus rhamnosus LRa05 Ameliorate Hyperglycemia through a Regulating Glucagon-Mediated Signaling Pathway and Gut Microbiota in Type 2 Diabetic Mice

In this study, we aimed to explore the antidiabetic effects of Lactobacillus rhamnosus LRa05 on glucose metabolism and gut microbiota in type 2 diabetes mellitus (T2DM) mice. Our data indicated that the fasting blood glucose levels were reduced by 53.5% after treatment with LRa05 at a dose of 10⁹ CFU·day^–1. Meanwhile, LRa05 attenuated insulin resistance, relieved hepatic oxidative stress, and alleviated metabolic lipopolysaccharide-related inflammation in T2DM mice. LRa05 promoted the expression of glucose transporter 2, while it inhibited the expression of glucagon receptor, glucose-6-phosphatase, cellular adenosine-3′-5′-cyclic monophosphate-dependent protein kinase, and phosphoenolpyruvate carboxykinase in diabetic mice. Meanwhile, LRa05 reshaped gut microbiota, resulting in increased short-chain fatty acid bacteria (Alloprevotella and Bacteroides) and decreased proinflammatory bacteria (Odoribacter and Mucispirillum). Thus, LRa05 may be used as a functional food supplement for modulating the disorder glucose metabolism and gut microbiota in T2DM.