Severity of Depressive Symptoms by Perceived Stress and Gut Microbiota Composition: A Sex‐Stratified Bayesian Approach in a Non‐Clinical Sample

Gut dysbiosis, an imbalance in gut microbiota, is increasingly linked to depression through the microbiota-gut-brain axis. Stress is an important risk factor for both gut dysbiosis and depression. Despite evidence of altered gut microbiota composition in patients with depression, little is known about how stress and specific gut microbiota features interact to influence depressive symptoms in healthy individuals. This study examined 398 healthy adults (241 women) who provided stool samples and completed validated questionnaires on perceived stress (PSS) and depressive symptoms (CES-D), with a focus on sex differences. In this sample, men and women were characterised by similar gut microbiota composition and diversity. Women reported higher PSS scores than men, whereas no differences were found in CES-D scores. Using Bayesian analyses, results showed that perceived stress predicted depressive symptoms in both sexes. Notably, in women, the genus Eubacterium moderated this relationship: higher perceived stress combined with lower Eubacterium abundance predicted more severe depressive symptoms. In contrast, no moderations by gut bacteria were found in men. The current results warrant further sex-specific investigations of the interaction between stress and specific gut microbiota features in influencing depressive symptoms and suggest that the genus Eubacterium might be a promising microbial biomarker associated with depressive symptoms, particularly in women under higher stress levels.