Smart CaCO-coated probiotics relieve constipation by enhancing intestinal motility and modulating microbial enzymes in a loperamide-induced rat model.

Abstract

Constipation is a prevalent gastrointestinal disorder often associated with impaired intestinal motility and unbalanced gut microbiota. Although probiotics offer therapeutic potential, their clinical efficacy is often limited by low gastric survival and inefficient intestinal release. Herein, we developed a novel smart delivery platform by encapsulating five probiotic strains within a single-layer calcium carbonate coating, designated as Probiotics Encapsulated with Calcium carbonate (PEC). This system is designed to respond to both pH and phosphate levels, enabling targeted intestinal probiotic delivery. Using a loperamide-induced constipation rat model, we evaluated the PEC therapeutic efficacy at three doses (15, 50, and 150 mg/kg). PEC administration significantly improved key constipation indicators, including defecation frequency, fecal moisture content, and intestinal transit rate in a dose-dependent manner. Furthermore, PEC selectively modulated harmful microbial enzymes such as β-glucuronidase and nitroreductase without adversely impacting the beneficial β-glucosidase enzyme. It also showed a trend to reduce systemic inflammatory markers, such as TNF-α and IL-1β. Notably, the high-dose PEC group restored most parameters to levels comparable to those of the normal group. These findings suggest that the PEC platform is a promising next-generation probiotic delivery system with potential to address some limitations of conventional probiotic therapy, such as low gastric survival and inefficient intestinal release. However, without dedicated control groups for calcium carbonate alone or uncoated probiotics, the specific contributions of the encapsulation cannot be fully isolated. PEC shows strong potential for development into functional foods and therapeutic agents targeting constipation and related gastrointestinal disorders.