Huangtu decoction alleviates chronic diarrhea of spleen-yang deficiency in mice by altering host metabolome and intestinal microbiota composition

Background: Huangtu decoction (HTD), a traditional Chinese medicine recipe, warms the spleen, nourishes the blood, and stops bleeding. It has been used to treat dysentery, gastrointestinal bleeding, diarrhea, and other symptoms caused by spleen-yang deficiency for more than 2,000 years in China. However, the mechanism underlying the treatment of chronic diarrhea due to spleen-yang deficiency (CDSD) using HTD remains unclear. Aims: : This study investigated whether HTD could mediate intestinal flora and serum metabolites to improve CDSD symptoms using a mouse model. Methods: : A CDSD mouse model induced by senna and an abnormal diet was constructed. The regulatory effects of HTD at 12.5, 25.0, and 50.0 g/kg/d on CDSD mice were assessed by measuring their bodyweight, diarrhea rate, loose stool rate, and histopathology. Changes inthe intestinal flora of CDSD mice were analyzed by 16S rRNA gene sequencing. Untargeted serum metabolomic analysis was performed using UHPLC-MS/MS. Results: : The results showed that HTD had a modulating effect on CDSD by reducing the weight loss, diarrhea rate, loose stool rate, and pathological damage. The intestinal flora analysis showed that HTD altered the community composition by decreasing the abundance of Allobaculum, Lactobacillus, and Ruminococcus. Serum metabolomics revealed that the ascorbate and aldarate metabolism, aldosterone synthesis and secretion, platelet activation, hypoxia-inducible factor 1 signaling pathway, inositol phosphate metabolism, phosphatidylinositol signaling, galactose metabolism, and alpha-linolenic acid metabolism were modulated after HTD treatment. Conclusion: HTD may alleviate CDSD symptoms by reducing weight loss, diarrhea rate, loose stool rate, and pathological damage caused by modeling and regulating intestinal flora and serum metabolites in CDSD mice.