Laxative Effect of Polysaccharides From Dendrobium officinale on Slow Transit Constipation: Regulation Effect of Intestinal Microbiota and 5‐HT System

Background Dendrobium officinale (DOF), a highly valued traditional Chinese medicinal herb and functional food, boasts a millennia‐long history of medicinal use. Our previous research has demonstrated its efficacy in alleviating acute constipation, primarily attributed to its polysaccharide (DOP). Nevertheless, the therapeutic potential of DOP in addressing slow transit constipation (STC) and its underlying mechanisms remain unexplored. This research seeks to elucidate the protective effects and underlying mechanistic pathways of DOP in loperamide‐induced STC. Methods KM mice were administered loperamide to establish the STC model, followed by DOP intervention. After treatment, gastrointestinal motility, fecal output, and key gastrointestinal regulatory hormones were all detected. The 5‐hydroxytryptamine (5‐HT) pathway was further analyzed by analyzing enterochromaffin cells (ECs), serotonin transport (SERT), and 5‐HT receptors (5‐HTRs). Additionally, 16S rDNA sequencing was performed to evaluate gut microbiota composition. Changes in levels of short‐chain fatty acids (SCFAs) and their receptor were also quantified. Results DOP significantly ameliorated defecation dysfunction in STC mice, enhancing gastrointestinal motility and increasing 24‐h fecal output. Additionally, DOP treatment restored the colonic levels of key gastrointestinal hormones, especially in 5‐HT concentration. This effect may be attributed to the expansion of ECs and suppression of SERT expression. Moreover, DOP selectively upregulated 5‐HT 4 R expression without affecting 5‐HT 3 R. Beyond neurotransmitter regulation, DOP modulated gut microbiota composition by increasing microbial diversity and altering the community structure, particularly through shifts in the Bacteroidetes/Firmicutes ratio. Furthermore, DOP elevated SCFA levels and activated their downstream receptor G Protein–Coupled Receptor 43 (GPR43), which may contribute to the observed 5‐HT system modulation. Conclusions DOP demonstrates significant efficacy in ameliorating constipation symptoms in STC mice through the dual modulation of the 5‐HT system and gut microbiota composition. These results furnish robust scientific support, substantiating the therapeutic potential of DOP in the daily health care or management of STC.