# The Modulatory Effects of Bacteroides thetaiotaomicron on Metabolic Parameters, Expression of Diabetes- and Inflammation-Related Genes and Gut Microbiota Composition in a Male Rat Model of Type 2 Diabetes Mellitus

## TL;DR

This study shows that Bacteroides thetaiotaomicron improves diabetes and inflammation markers and alters gut bacteria in a rat model of type 2 diabetes.

## Contribution

The study demonstrates the novel therapeutic potential of Bacteroides thetaiotaomicron in modulating diabetes-related genes and gut microbiota in T2DM.

## Key findings

- B. thetaiotaomicron reduced body weight, blood glucose, insulin, and lipid levels in diabetic rats.
- The bacterium modulated gene expression of PI3K, Akt, and inflammatory markers like IL-6 and IL-10.
- Gut microbiota composition shifted with increased Bacteroidota and Faecalibacterium prausnitzii.

## Abstract

Type 2 diabetes mellitus (T2DM) is a prevalent disorder with significant complications and mortality. Gut microbiota plays a role in metabolic homeostasis, and dysbiosis may contribute to inflammation and insulin resistance (IR).

This study aimed to investigate the effect of Bacteroides thetaiotaomicron on glycemic and IR markers, lipid profiles, and the expression of diabetes- and inflammation-related genes, as well as the abundance of targeted gut microbiota in a rat model of T2DM.

Thirty-two male Wistar rats were randomly assigned to normal control groups or a high-fat diet/streptozotocin-induced T2DM group. Each group received 5-week oral B. thetaiotaomicron (1×109 CFU/mL) or phosphate-buffered saline (PBS). Anthropometric and metabolic measures were compared pre- and post-intervention. Expression of diabetes-related genes (PI3K, Akt) in the liver, inflammation-related genes (IL-6, IL-10, IL-1β, IL-4) in the colon, cannabinoid receptors (CB1, CB2) in both tissues, and changes in gut microbiota composition were evaluated using quantitative PCR.

Compared to the T2DM-PBS group, administration of B. thetaiotaomicron to T2DM rats led to significant reductions in body weight (BW) (8%), Body Mass Index (BMI) (21%), Lee index (10%), fasting blood glucose (FBG) (16%), insulin (46%), homeostatic model assessment of IR (HOMA-IR) (56%), triglycerides (TG) (34%), total cholesterol (TC) (29%), and low-density lipoprotein cholesterol (25%) (all P ≤ 0.012). This intervention was associated with reduced expression of CB1 (1.81-fold) and increased expression of PI3K (4.91-fold), Akt (3.55-fold), and CB2 (2.26-fold) (all P < 0.0001). Furthermore, expression of IL-1β (1.76-fold), IL-6 (2.10-fold), and CB1 (1.64-fold) was significantly down-regulated, whereas expression of other inflammation-related genes including IL-4 (2.43-fold), CB2 (1.47-fold), and IL-10 (4.6-fold) was up-regulated (all P ≤ 0.0009). Moreover, significant changes in targeted gut microbiota were observed (a reduction in the abundance of Bacillota and Actinomycetota and an increase in Bacteroidota, Faecalibacterium prausnitzii, B. thetaiotaomicron, and Clostridium cluster IV).

Bacteroides thetaiotaomicron improved anthropometric measures, glycemic indices, IR, lipid profiles, and regulated the expression of diabetes- and inflammation-related genes, along with modification of gut microbiota composition in a T2DM rat model.