Pasteurized Bacteroides thetaiotaomicron and its extracellular vesicles improve metabolic profiles, expression of genes associated with diabetes and inflammation, and gut microbiota in type 2 diabetic rats

This study investigates the effect of pasteurized Bacteroides thetaiotaomicron (PB.t) and its extracellular vesicles (B.t-EVs) on metabolic parameters, diabetes- and inflammation-related gene expression, and microbiota composition in type 2 diabetes mellitus (T2DM). A total of forty-eight male Wistar rats were randomly divided into normal controls (NC, n=24) and T2DM-induced rats (n=24), and each group was further subdivided to receive phosphate-buffered saline (PBS), PB.t, or B.t-EVs by gavage daily for five consecutive weeks. The effects on obesity indices, glycemic markers, lipid profile, expression of diabetes- and inflammation-related genes in the liver and colon, and targeted changes in gut microbiota were assessed. Treatment with B.t-EVs and PB.t was associated with reductions in obesity indices (body weight, body mass index, and Lee index) and fasting blood glucose compared to the T2DM-PBS group; however, this reduction was significant only in T2DM-B.t-EVs rats (P≤0.0142). Both interventions yielded significant improvements in metabolic parameters, as demonstrated by decreased serum insulin, triglyceride, and total cholesterol levels, reduced homeostatic model assessment for insulin resistance (HOMA-IR), and improved glucose tolerance (all P≤0.0382). Both treatments reduced with downregulation of endocannabinoid system receptor 1 (CB1) expression and increased CB2 and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) gene expression in the liver (all P≤0.0018). In the colon, PB.t and B.t-EVs significantly downregulated interleukin (IL)-1β, IL-6, and CB1 genes. They also upregulated IL-4, IL-10, and CB2 genes (all P≤0.0004). Targeted microbiota analysis showed increased abundances of Bacteroidetes, Faecalibacterium prausnitzii, and B.t, accompanied by a reduced level of Firmicutes, Actinobacteria and Firmicutes/Bacteroidetes (F/B) ratio (P≤0.0492). Additionally, treatment with B.t-EVs increased the abundance of Clostridium cluster IV (P=0.0085). Histological findings indicated reduced pancreatic damage in the treated groups. Altogether, these results suggest that PB.t and B.t-EVs, as paraprobiotic and postbiotic candidates, may improve metabolic health, reduce inflammation, and modulate gut microbiota composition in T2DM.