Therapeutic potential of Sishen Pill: modulating intestinal mucosal microbiota and barrier function in IBS-D with Spleen-Kidney Yang Deficiency

This study aimed to investigate the intestinal microecological mechanisms underlying the effects of Sishen Pill (SSP) on diarrhea-predominant irritable bowel syndrome (IBS-D) with Spleen-Kidney Yang Deficiency Syndrome, thereby providing experimental evidence for clinical management. Murine models of IBS-D characterized by Spleen-Kidney Yang insufficiency were established in SPF-grade female Kunming mice by Folium senna-adenine gavage in conjunction with restraint-tail clamping. Experimental groups received SSP decoction or pinaverium bromide suspension. Intestinal morphological changes were assessed via Alcian blue staining. The concentrations of serum D-lactate and diamine oxidase were measured through enzyme-linked immunosorbent assay. The intestinal mucosal microbiota was analyzed using 16S rRNA gene sequencing. The model mice exhibited reduced anal temperatures, diarrhea, weight loss, intestinal mucosal barrier injury, and altered mucosal microbiota. SSP treatment alleviated these abnormalities, decreased serum D-LA and DAO levels, and improved the intestinal mucosal structure. Microbiota analysis identified Alkaliphilus as a potential genus associated with SSP intervention, while Streptococcus and Maribacter were correlated with intestinal barrier indicators. These findings suggest that SSP may improve IBS-D with Spleen-Kidney Yang Deficiency by modulating the intestinal mucosal microbiota and restoring mucosal barrier function.