Wu Wenjing, Li Shuhan, Ye Zengjie
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian Province, China.
School of Nursing, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China.
J Affect Disord. 2025 Apr 1;374:150-159. doi: 10.1016/j.jad.2025.01.050. Epub 2025 Jan 12.
Extensive research indicates a link between gut microbiota dysbiosis and psychiatric disorders. However, the causal relationships between gut microbiota and different types of psychiatric disorders, as well as whether inflammatory factors mediate these relationships, remain unclear.
We utilized summary statistics from the largest genome-wide association studies to date for gut microbiota (n = 18,340 in MiBioGen consortium), circulating inflammatory factors (n = 8293 for 41 factors and n = 14,824 for 91 factors in GWAS catalog), and six major psychiatric disorders from the Psychiatric Genomics Consortium (PGC): attention deficit hyperactivity disorder (ADHD, n = 38,691), anxiety disorder (ANX, n = 2248), bipolar disorder (BIP, n = 41,917), anorexia nervosa (AN, n = 16,992), schizophrenia (SCZ, n = 36,989), and autism spectrum disorder (ASD, n = 18,381). We conducted bidirectional Mendelian randomization (MR) analysis to explore the causal relationships between gut microbiota and psychiatric disorders. Additionally, we performed two-step MR and multivariable MR (MVMR) analyses to identify potential mediating inflammatory factors.
We found significant causal relationships between 11 gut microbiota and ADHD, 2 gut microbiota and ANX, 11 gut microbiota and BIP, 8 gut microbiota and AN, 15 gut microbiota and SCZ, and 5 gut microbiota and ASD. There were 16 positive and 15 negative causal effects between inflammatory factors and psychiatric disorders. Furthermore, MVMR analysis results indicated that the correlation between genus Roseburia and ADHD was mediated by MCSF, with a mediation proportion of 3.3 %; the correlation between genus Erysipelotrichaceae UCG003 and BIP was mediated by GDNF, with a mediation proportion of 3.7 %; and the correlation between family Prevotellaceae and SCZ was mediated by CD40, with a mediation proportion of 8.2 %.
The MR analysis results supported causal relationships between gut microbiota and six psychiatric disorders, as well as the potential mediating role of inflammatory factors. This study highlights the potential role of the gut microbiota-inflammation-brain axis in psychiatric disorders.
广泛的研究表明肠道微生物群失调与精神疾病之间存在联系。然而，肠道微生物群与不同类型精神疾病之间的因果关系，以及炎症因子是否介导这些关系仍不清楚。
我们利用了迄今为止最大规模的全基因组关联研究的汇总统计数据，涉及肠道微生物群（微生物组整合联盟中的18340例）、循环炎症因子（GWAS目录中41种因子的8293例和91种因子的14824例），以及精神基因组学联盟（PGC）的六种主要精神疾病：注意力缺陷多动障碍（ADHD，38691例）、焦虑症（ANX，2248例）、双相情感障碍（BIP，41917例）、神经性厌食症（AN，16992例）、精神分裂症（SCZ，36989例）和自闭症谱系障碍（ASD，18381例）。我们进行了双向孟德尔随机化（MR）分析，以探索肠道微生物群与精神疾病之间的因果关系。此外，我们进行了两步MR和多变量MR（MVMR）分析，以确定潜在的介导炎症因子。
我们发现11种肠道微生物群与ADHD、2种肠道微生物群与ANX、11种肠道微生物群与BIP、8种肠道微生物群与AN、15种肠道微生物群与SCZ以及5种肠道微生物群与ASD之间存在显著的因果关系。炎症因子与精神疾病之间有16种正向和15种负向因果效应。此外，MVMR分析结果表明，罗氏菌属与ADHD之间的相关性由巨噬细胞集落刺激因子（MCSF）介导，介导比例为3.3%；丹毒丝菌科UCG003属与BIP之间的相关性由胶质细胞源性神经营养因子（GDNF）介导，介导比例为3.7%；普雷沃氏菌科与SCZ之间的相关性由CD40介导，介导比例为8.2%。
MR分析结果支持肠道微生物群与六种精神疾病之间的因果关系，以及炎症因子的潜在介导作用。本研究强调了肠道微生物群-炎症-脑轴在精神疾病中的潜在作用。
