Intestinal microbial remodeling and metabolite regulation may be related to the improvement of social avoidance in depressed mice by Modified Xiaoyaosan

作者：Ting Linghu, Ting Hu, Zhenning Wu, Qi Wang, Yu Zhao, Yujing Wang, Li K, Xuemei Qin, Junsheng Tian, R Zhang · 发表于：Frontiers in Microbiology · 年份：2026 · DOI：10.3389/fmicb.2026.1774975 · 研究领域：Gut microbiota and health、Tryptophan and brain disorders、Amino Acid Enzymes and Metabolism

Background Increased intestinal permeability is implicated in the pathogenesis of depression. Modified Xiaoyaosan (MXYS) has demonstrated antidepressant-like effects in chronic social defeat stress (CSDS) mice, particularly in improving social avoidance behavior. However, direct evidence that MXYS improves depressive behavior by regulating intestinal permeability remains lacking. Methods Using a CSDS-induced depression mouse model, we investigated the effects of MXYS through an integrated multi-omics approach, combining intestinal histopathology, microbiome, metabolomics, and molecular biology techniques. This strategy allowed systematic assessment of pathological changes, gut microbial composition, metabolite profiles, and protein expression. Results MXYS treatment significantly alleviated social avoidance behavior in CSDS mice. It upregulated the expression of tight junction proteins in the colon, jejunum, and hippocampus. MXYS also reduced serum permeability markers of lipopolysaccharide (LPS), D-lactate (D-Lac), and diamine oxidase (DAO), as well as concentrations of pro-inflammatory cytokines TNF-α and IL-1β in both intestinal tissues and the hippocampus. Gut microbiota analysis revealed that MXYS notably decreased the relative abundance of Desulfovibrio in the colon, which was associated with modulation of β-alanine metabolism. In the jejunum, MXYS increased the relative abundance of Clostridium sp. mbf VZ-132 and influenced glycerophospholipid metabolism. Conclusion MX...