Screening of Potential Probiotic Lactobacillaceae and Their Improvement of Type 2 Diabetes Mellitus by Promoting PI3K/AKT Signaling Pathway in db/db Mice

The study aimed to isolate Lactobacillaceae strains with in vitro hypoglycemic activity and probiotic properties and to determine their antidiabetic abilities in vivo. Lactiplantibacillus plantarum 22, L. plantarum 25, Limosilactobacillus fermentum 11, and L. fermentum 305 with high in vitro hypoglycemic activity were screened from 23 strains of Lactobacillaceae isolated from human feces and identified by 16S rDNA sequencing. The fasting blood glucose (FBG) of the mice was recorded weekly. After 12 weeks, liver, kidney, and pancreas tissues were stained with hematoxylin and eosin (H&E) to observe histomorphology; the inflammatory factors were assayed by Quantitative Real-time PCR; PI3K and AKT were measured by Western blot; the short-chain fatty acids (SCFAs) were determined by LC-MS/MS. Inhibitory activities of L. plantarum 22, L. plantarum 25, L. fermentum 11, and L. fermentum 305 against α-amylase were 62.29 ± 0.44%, 51.81 ± 3.65%, 58.40 ± 1.68%, and 57.48 ± 5.04%, respectively. Their inhibitory activities to α-glucosidase were 14.89 ± 0.38%, 15.32 ± 0.89%, 52.63 ± 3.07%, and 51.79 ± 1.13%, respectively. Their survival rate after simulated gastrointestinal test were 12.42 ± 2.84%, 9.10 ± 1.12%, 5.86 ± 0.52%, and 8.82 ± 2.50% and their adhesion rates to Caco-2 cell were 6.09 ± 0.39%, 6.37 ± 0.28%, 6.94 ± 0.27%, and 6.91 ± 0.11%, respectively. The orthogonal tests of bacterial powders of the four strains showed that the maximum inhibitory activities to α-amylase and α-glucosidase were 93.18 ± 1.19% and 75.33 ± 2.89%, respectively. The results showed that the mixture of Lactobacillaceae could lower FBG, reduce inflammation, and liver, kidney, and pancreas damage, promote PI3K/AKT signaling pathway, and increase the content of SCFAs. The combination of L. plantarum 22, L. plantarum 25, L. fermentum 11, and L. fermentum 305 can potentially improve type 2 diabetes mellitus (T2DM). [Figure: see text]