Altered serum 3β-hydroxy bile acids in major depressive disorder and associations with symptom dimensions

Bile acids are gut microbiota-derived signaling molecules that participate in gut-brain axis communication, and mounting evidence implicates altered bile acid metabolism and associated gut-brain axis dysfunction in major depressive disorder (MDD). Here we investigated if serum 3β-hydroxy bile acid profiles are abnormal in MDD and associated with symptom dimensions. Ninety MDD patients and 74 healthy controls were recruited. Serum concentrations of nine bile acids, including 3β-cholic acid (3β-CA) and 3β-deoxycholic acid (3β-DCA), were measured by LC/MS-MS. The Oxidative Stress Index (OSI) was calculated as the ratio of 3-oxo derivatives to 3β-isomers. Symptoms were assessed using the Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale, and Social Disability Screening Schedule-17 (SDSS-17). Associations between bile acid concentrations and symptoms were assessed by Spearman's correlation analysis, while the ability of bile acid concentrations to predict MDD status was evaluated by receiver operating characteristic (ROC) analysis. Patients exhibited significantly lower serum 3β-CA (Z = -3.223, P = 0.001) and 3β-DCA (Z = -2.895, P = 0.004), and elevated serum OSI (Z = -2.359, P = 0.018). Serum 3β-CA was negatively correlated with HAMD cognitive disturbance score (β = -0.219, P = 0.038), while OSI was positively correlated with SDSS-17 score (β = 0.375, P < 0.001). No significant associations were found between bile acid measures and anxiety symptoms (all P > 0.05). Areas under the ROC curves were 0.646 for 3β-CA, 0.632 for 3β-DCA, and 0.607 for OSI. Lower circulating 3β-hydroxy bile acids and elevated oxidative metabolism are associated with cognitive impairment and social dysfunction in MDD, suggesting gut-brain axis involvement in MDD pathophysiology.