Lactobacillus plantarum RG-034 colonic soluble capsules alleviate functional constipation in rats by promoting short-chain fatty acid generation

Abstract

Functional constipation is a chronic gastrointestinal disorder that significantly impacts quality of life and healthcare costs. Current treatments have limitations such as self-management difficulty and intestinal damage. This study evaluated the efficacy of Lactobacillus plantarum RG-034, a probiotic delivered via colonic soluble capsules, in alleviating loperamide-induced functional constipation in rats. Our findings demonstrate that 28-day RG-034 administration exhibited no significant organ toxicity. Pharmacodynamic results indicated that RG-034 improved stool frequency, characteristics, and water content and accelerated intestinal transit in constipated rats, along with enhancing colonic contraction and relaxation tension in isolated colons. Moreover, RG-034 promoted the proliferation of interstitial cells of Cajal (ICCs) and enhanced cellular calcium ion uptake by upregulating the PI3K/AKT pathway. Additionally, RG-034 positively modulated gut microbiota by increasing the abundance of Muribaculaceae and promoting short-chain fatty acid (SCFA) production. Co-culturing RG-034 with rat feces in vitro demonstrated a significant increase in SCFAs in the supernatant. Subsequent exposure of primary ICCs to this co-culture supernatant indicated that RG-034 facilitates calcium ion influx and promotes cell proliferation, an effect that was reversible with the application of PI3K inhibitors. These findings suggest that Lactobacillus plantarum RG-034 colonic soluble capsules enhance SCFA synthesis to promote PI3K/AKT phosphorylation, which in turn stimulates ICC proliferation and intestinal relaxation and contraction, thereby alleviating constipation symptoms.