Gut microbiota dysbiosis and metabolic perturbations of bile/glyceric acids in major depressive disorder with IBS comorbidity

作者：Jinglong Du, Zhen-Jie Zhang, Li Tan, H. J. Yang, Runnan Yang, Yilong Chen, Guifeng Tan, Jing Li, Wenjing Li, Lin Yang, Jia Cai, Dan-Lin Shen, Hongru Zhu, Zhenxin Fan, Minlan Yuan, Wei Zhang · 发表于：mBio · 年份：2025 · DOI：10.1128/mbio.02447-25 · 被引用次数：6 · 研究领域：Gut microbiota and health、Diet and metabolism studies、Tryptophan and brain disorders

ABSTRACT Major depressive disorder (MDD) and irritable bowel syndrome (IBS) exhibit high comorbidity, yet their shared pathophysiology remains unclear. Previous studies have primarily focused on the psychological health in the IBS population, without considering psychiatric diagnoses or stratifying different psychological states, potentially leading to biased findings. This study employed multi-omics approaches to characterize gut microbiota and serum metabolites in 120 MDD patients (47 with IBS and 73 without IBS) and 70 healthy controls (HCs). MDD with IBS patients showed significantly higher depression (Hamilton depression scale [HAMD-17]) and anxiety (Hamilton anxiety scale [HAMA-14]) scores than MDD-only patients ( P < 0.05). Metagenomic sequencing of fecal samples revealed increased alpha diversity (Chao1/Shannon indices) and Firmicutes dominance in both MDD groups vs HC, while Actinobacteria enrichment specifically marked MDD with IBS. Functionally, MDD with IBS uniquely activated D-amino acid/glycerolipid metabolism pathways (Kyoto Encyclopedia of Genes and Genomes). Serum metabolomics identified comorbid-specific perturbations: downregulation of bile acids (CDCA, GCDCA, GCDCA-3S) and upregulation of glyceric acid/glutaconic acid. Our study also found that Eggerthella lenta and Clostridium scindens are differentially abundant bacteria that are involved in bile acid metabolism, and that microbial genes (e.g., K03738) are associated with glyceric acid production. The...