High-sensitivity C-reactive protein modulates the association between antimicrobial resistance genes pathway and depressive symptoms in first-episode and drug-naïve patients with major depressive disorder

Gut dysbiosis and systemic inflammation are robustly associated with major depressive disorder (MDD), but the relationship between the gut microbiota, their metabolic pathways and inflammation remains unclear in MDD. We enrolled 61 first-episode and drug-naïve patients with MDD and 33 matched healthy controls(HC). Participants data included demographic data, serum inflammatory indices high-sensitivity C-reactive protein (hs-CRP), white blood cells (WBC), neutrophils, lymphocytes, monocytes, eosinophils, basophils), and gut microbiota (metagenomics sequencing) were involved; depressive symptoms were assessed by the 17-item Hamilton Depression Rating Scale (HAMD-17) in patients. Compared with HC, patients with MDD exhibited elevated hs-CRP levels, significant dysregulation of 27 taxa and 7 microbial metabolic pathways. At the species level, our findings suggest a selective enrichment of Ruminococcus bicirculans , Actinomyces sp. ICM47 and Alistipes finegoldii in patients with MDD relative to HC. Additionally, the scores of HAMD-17 were inversely correlated with both the abundance of Fusobacterium mortiferum and the relative abundance of the antimicrobial resistance genes pathway. A moderation analysis suggested that the association between the antimicrobial resistance genes pathway and depressive symptoms varied with serum hs-CRP levels in an exploratory statistical model, though this finding requires independent replication. This study demonstrates that the serum of hs-CRP may influence the association between the antimicrobial resistance genes pathway and depressive symptoms, suggesting that low-grade inflammation may interact with intestinal metabolic pathways in the context of MDD. However, the causal direction linking microbial metabolic pathways to depressive symptoms remains to be clarified. Not applicable.