Biomarker analysis revealed significantly reduced levels of IL-6 (p = 0.007), IL-1β (p = 0.002), TNF-α (p = 0.005) and CRP (p = 0.001) in the combination group, and IL-6 and CRP showed strong positive correlations with depression scores (r = 0.35-0.39).<h4>Conclusions</h4>This study confirms that modulating the intestinal smicroecology can enhance antidepressant efficacy by reducing neuroinflammation. Here, CRP is linked to major depressive disorder.