Multi‐Omics Integration Reveals Gut Microbiota‐Bile Acid Crosstalk Underlying Baizhu Shaoyao Decoction's Therapeutic Efficacy in Weaning Stress of Piglets

Diarrhea is common in infants, particularly children less than 2 years old. Intractable or protracted infancy diarrhea is typically associated with feeding intolerance and malabsorption that is lethal for newborns. The objective of this study is to explore the regulatory effects of baizhu shaoyao decoction (BSD) on the gut microbiota and associated metabolites in weaned piglets, thereby elucidating the mechanism by which BSD mitigates weaning stress in piglets. Piglets were allocated into five groups, with each group receiving designated medication for a continuous 14-day period: control, zaohu powder, as well as low-, medium-, and high-dose BSD groups (n = 6 piglets per group). To identify diarrhea-related biomarkers, microbial communities, functions, and metabolites were compared between the early-weaned piglets (control group) and those treated with 1.28 g/kg BSD (medium-dose BSD group). Our findings revealed significant shifts in microbial composition, function, and metabolic profiles in piglets from the medium-dose BSD group, intricately associated with the host's diarrhea status. Furthermore, carbohydrate metabolism and biosynthesis, lipid and amino acid metabolism, glycan activity, and carbohydrate digestive enzymes exhibited downregulation in piglets of the medium-dose BSD group compared to those in the control group. Transcriptome analysis highlighted the pivotal role of the FoxO1/3 transcription factor in mitigating weaning stress, particularly through the augmentation of CD4+/CD8+ T cell proportions. Our findings underscored that therapeutic effects of BSD on weaning stress involve intestinal barrier restoration, modulation of brain-gut peptide expression, and a reduction in mast-cell activity in the ileum. BSD has a significant effect on improving early weaning diarrhea in infants. Its mechanism of action involves improving the abundance of key intestinal microbiota Lachnospiraceae_bacterium, affecting changes in intestinal bile acid metabolites (such as, chenodeoxyglycocholic acid, glycochenodeoxycholic acid) and thereby regulating intestinal mucosal immunity and gut-brain peptides, achieving the effect of treating weaning stress.