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

TL;DR

This study shows that pasteurized Bacteroides thetaiotaomicron and its extracellular vesicles can improve metabolism, reduce inflammation, and alter gut bacteria in diabetic rats.

Contribution

The novel contribution is demonstrating the therapeutic potential of paraprobiotic and postbiotic forms of Bacteroides thetaiotaomicron in type 2 diabetes.

Findings

PB.t and B.t-EVs reduced obesity indices and fasting blood glucose in T2DM rats.

Both treatments improved metabolic parameters and modulated gut microbiota composition.

Treatments reduced inflammation by altering gene expression in the liver and colon.

Abstract

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.

See also the graphical abstract(Fig. 1).

Figures