Zhang Qi, Zhao Wenxuan, Yun Yajun, Ma Ting, An Huimei, Fan Ning, Wang Jun, Wang Zhiren, Yang Fude
The Affiliated Mental Health Center of Jiangnan University, Wuxi Central Rehabilitaion Hospital, Wuxi, China.
Beijing HuiLongGuan Hospital, Peking University HuiLongGuan Clinical Medical School, Beijing, China.
J Affect Disord. 2025 Mar 15;373:273-283. doi: 10.1016/j.jad.2024.12.070. Epub 2024 Dec 21.
Cognitive impairment occurs throughout the entire course of and affects the work and life of patients with major depressive disorder (MDD). The gut microbiota, kynurenine pathway (KP) and inflammatory response may have important roles in the mechanism of cognitive impairment in MDD patients. Consequently, our goal was to investigate the association among the gut microbiota, inflammation, KP, and cognition in MDD.
We enrolled patients with MDD (N = 86) and healthy controls (HCs, N = 120) in this research. The study involved participant data regarding the levels of serum inflammatory factors (interleukin [IL]-1β, IL-4, IL-6, brain-derived neurotropic factor [BNDF], migration inhibitory factor [MIF], tumor necrosis factor [TNF]-α, vascular endothelial growth factor [VEGF]), gut microbiota and cognitive function (MCCB) were collected.
Patients demonstrated poorer cognitive function. Gut microbiota, such as Bacteroide, Prevotella, Faecalibacterium and Parabacteroides between MDDs and HCs were significantly different. Moreover, in patients with MDD, we found that different microbiomes were related to cognition and that Acidaminococcus was positively correlated with multiple domains of cognition. Allisonella and Acidaminococcus were significantly positively correlated with BDNF and negatively correlated with MIF. Alloprevotella, Blautia, and Megamonas were positively correlated with kynurenine/tryptophan (KYN/TRP). Acidaminococcus was negatively correlated with 3-hydroxykynurenine (3-HK). BDNF levels was significantly positive correlated with kynurenic acid (KA) and quinolinic acid (QA).
The results of the present study suggest that the gut microbiota is associated with cognitive function, cytokine levels and KP metabolism in patients with MDD; however, the mechanism of the interaction between cognition and gut microbiota in MDD patients require further investigation.
认知障碍贯穿重度抑郁症（MDD）的整个病程，并影响患者的工作和生活。肠道微生物群、犬尿氨酸途径（KP）和炎症反应可能在MDD患者认知障碍的机制中起重要作用。因此，我们的目标是研究MDD患者肠道微生物群、炎症、KP和认知之间的关联。
本研究纳入了MDD患者（N = 86）和健康对照者（HCs，N = 120）。该研究收集了参与者关于血清炎症因子（白细胞介素[IL]-1β、IL-4、IL-6、脑源性神经营养因子[BNDF]、迁移抑制因子[MIF]、肿瘤坏死因子[TNF]-α、血管内皮生长因子[VEGF]）水平、肠道微生物群和认知功能（MCCB）的数据。
患者表现出较差的认知功能。MDD患者和HCs之间的肠道微生物群，如拟杆菌属、普雷沃菌属、粪杆菌属和副拟杆菌属存在显著差异。此外，在MDD患者中，我们发现不同的微生物群与认知相关，酸氨基球菌与多个认知领域呈正相关。阿利森菌属和酸氨基球菌与BDNF呈显著正相关，与MIF呈负相关。嗜胆菌属、布劳特氏菌属和巨单胞菌属与犬尿氨酸/色氨酸（KYN/TRP）呈正相关。酸氨基球菌与3-羟基犬尿氨酸（β-HK）呈负相关。BDNF水平与犬尿酸（KA）和喹啉酸（QA）呈显著正相关。
本研究结果表明，肠道微生物群与MDD患者的认知功能、细胞因子水平和KP代谢相关；然而，MDD患者认知与肠道微生物群之间相互作用的机制需要进一步研究。
