Integrated UHPLC-MS/MS and 16S rRNA sequencing reveals that Weiling Decoction alleviates spleen deficiency with...

Spleen deficiency with dampness pattern (SDDP) diarrhea is a prevalent gastrointestinal disorder, yet the therapeutic mechanisms of the clinically effective Weiling Decoction (WLD) require further elucidation. In this study, an SDDP model was established in Kunming mice via high-humidity exposure and oral lard administration. The chemical profile of WLD was characterized using UHPLC-MS/MS, which identified twenty primary bioactive compounds, including vicenin-1, inosine, and chlorogenic acid. Therapeutic efficacy was evaluated through histological and biochemical assays, demonstrating that WLD promoted the restoration of small intestinal villus length and increased the number of goblet cells per unit area. Furthermore, WLD elevated serum cAMP, D-xylose, and gastrin levels while reducing serum cGMP and vasoactive intestinal peptide (VIP) levels. To investigate microecological mechanisms, 16S rRNA sequencing was utilized, revealing that WLD significantly increased the relative abundances of Limosilactobacillus, Dwaynesavagella, and Paramuribaculum in the small intestinal contents. Additionally, PICRUSt2 was applied to predict functional shifts in microbial metabolic pathways, suggesting that secondary bile acid biosynthesis may be a critical mechanistic pathway for treating SDDP diarrhea. Collectively, WLD alleviates SDDP diarrhea by modulating the intestinal microbiota and restoring the host's gastrointestinal-water-energy regulatory network; these correlative findings suggest a microbiota-associated pharmacological mechanism, providing a biotechnological basis for the "syndrome-matched" treatment of gastrointestinal disorders.

The online version contains supplementary material available at https://doi.org/10.1007/s13205-026-05052-y.