A new perspective on cognitive impairment in major depressive disorder: Changes in gut microbiota and their inflammatory regulatory mechanisms.

BACKGROUNDCognitive impairments in major depressive disorder (MDD) affect patients' social functioning, with underlying mechanisms involving gut microbiota and inflammatory factors remaining unclear.

METHODSThe study analyzed cognitive function, gut microbiota changes, and inflammatory factor levels in 39 unmedicated MDD patients and 41 healthy controls, employing correlation and moderation effect analysis.

RESULTSMDD patients scored lower than controls in cognitive functions like information processing speed, attention/vigilance, verbal learning, visual learning and social cognition. They showed reduced gut microbiota diversity and increased levels of inflammatory markers (TNF-α, IL-1, IL-6, IL-17, IL-27, IL-33). Sellimonas abundance correlated negatively with attention/vigilance, moderated by TNF-α, IL-27, and IL-33. This relationship was stronger at lower inflammation levels.

CONCLUSIONSMDD patients exhibit multi-domain cognitive dysfunction alongside pro-inflammatory states and disrupted gut microbiota. The abundance of Sellimonas significantly predicts attention/vigilance deficits. Inflammatory factors modulate the impact of gut microbiota on cognitive function, suggesting chronic low-grade inflammation as a key risk factor for cognitive impairment in MDD.