Chinese Yam ( Dioscorea ) Improves Psychiatric Comorbidities of Colitis Mice Through Regulating 5‐HT Metabolism

ABSTRACT Chinese yam ( Dioscorea , CY) is a traditional medicinal and edible plant with potential health benefits. This study aimed to explore the therapeutic effects of CY on colitis and associated psychiatric comorbidities in DSS‐induced mice models, using oral administration of CY powder at 6.0 g/kg body weight per day. Supplementation with CY significantly alleviated colonic mucosal damage and reduced serum LPS levels, indicating improved gut barrier integrity. Behavioral phenotyping assays and hippocampal morphology further revealed that CY ameliorated anxiety and depressive symptoms. Mechanistically, CY inhibited the NFκB/NLRP3 signaling pathway, thereby suppressing neuroinflammation——a key mediator linking intestinal and CNS inflammation. Targeted metabolomics combined with transcriptional analysis was employed to investigate serotonin (5‐HT) metabolism. Notably, CY supplementation upregulated colonic TPH1 and cerebral Maoa expression, increased levels of peripheral CD4 + T lymphocytes, and reversed DSS‐induced reductions of fecal 5‐HT, 5‐HTP, and 5‐HIAA. Additionally, CY normalized HPA axis dysfunction by downregulating HTR2C expression in the brain. These findings suggest that CY alleviates IBD‐related mood disorders by maintaining gut mucus barrier, suppressing neuroinflammation, and restoring serotonergic homeostasis via the gut–brain axis.