Polygonatum cyrtonema Polysaccharide Ameliorates Functional Constipation in Mice via the Gut Microbiota–Pentadecanoic Acid–GPR40 Axis

Abstract

Constipation is a widespread gastrointestinal dysfunction that severely diminishes life satisfaction, yet current pharmacological interventions frequently carry risks of dependency. This study investigates the therapeutic potential and underlying mechanism ofPolygonatum cyrtonema polysaccharide (PCP), an inulin neoseries-type fructan, in mitigating loperamide-induced constipation in mice. Our results demonstrated that PCP treatment significantly normalized defecation indicators, including increased fecal water content and accelerated small-intestinal transit. Fecal microbiota transplantation (FMT) confirmed that the anti-constipation efficacy of PCP was driven by the gut microbiota. Integrated 16S rRNA sequencing and metabolomic profiling revealed that PCP remodeled the gut microbiota, particularly enriching Lachnospiraceae, which subsequently drove the accumulation of pentadecanoic acid (PDA). Mechanistically, PDA served as a key microbial metabolite that enhanced colonic motility, likely by activating the GPR40 receptor. These findings identify the “PCP–microbiota–PDA–GPR40” axis as an novel pathway for alleviating functional constipation, supporting PCP as a promising prebiotic candidate or functional food ingredient.