Journal of Exercise & Organ Cross Talk

Abstract This study investigated the effects of high-intensity interval training (HIIT) and a multi-strain probiotic mixture, on the intestinal expression of FXR and PPAR-γ in a rat model of type 2 diabetes mellitus (T2DM). Forty male Wistar rats were randomly assigned to five groups (n=8): Healthy Control (HC), Diabetic Control (DC), Diabetic+HIIT (DH), Diabetic+Probiotic (DP), and Diabetic+HIIT+Probiotic (DHP). T2DM was induced via a single intraperitoneal injection of nicotinamide (95 mg/kg) followed by streptozotocin (STZ, 55 mg/kg). The HIIT protocol was performed on a rodent treadmill for 8 weeks (5 sessions/week). The probiotic mixture (Lactobacillus rhamnosus GG, Lactobacillus casei, Lactobacillus reuteri; 1×10¹⁰ CFU/mL each) was administered daily via oral gavage. Diabetes induction significantly downregulated the intestinal expression of both FXR and PPAR-γ compared to healthy controls (p<0.001). HIIT and probiotic interventions, individually, significantly increased the expression of both nuclear receptors compared to the diabetic control group (p<0.001). Notably, the combined HIIT and probiotic intervention (DHP) produced the highest expression levels of FXR and PPAR-γ, which were significantly greater than either intervention alone (p<0.01) and restored FXR expression to levels comparable to healthy controls. Both HIIT and multi-strain probiotic supplementation effectively upregulate the intestinal expression of FXR and PPAR-γ in diabetic rats, with the combination exerting a synergistic effect. These findings identify a novel mechanism by which lifestyle interventions may restore intestinal metabolic function and inter-organ communication in T2DM, highlighting the therapeutic potential of targeting the gut through combined exercise and probiotic strategies.