Huang Zijin, Du Xueke, Li Fangzhou, Lan Zhixuan, Guo Liang, Pan Linghui
Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China.
Department of Anesthesiology, The Second Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530007, People's Republic of China.
Metab Brain Dis. 2025 Apr 12;40(4):178. doi: 10.1007/s11011-025-01611-z.
Changes in hippocampal volume (HV) are linked to various neuropsychiatric disorders. Observational studies suggest associations of gut microbiota (GM) and blood metabolites (BM) with changes in HV; however, their causal relationships remain unclear. We aimed to use Mendelian randomization (MR) to investigate the causal associations of GM and BM with changes in HV and to explore the potential mediating role of BM. Using two-sample MR (TSMR) analysis, we examined 412 GM traits and 1,400 BM traits with a focus on their causal relationships with age-independent/dependent longitudinal changes in HV, primarily using the inverse variance weighted method. Furthermore, we explored the mediating role of BM through a two-step MR design. We identified 44 GM traits and 175 BM traits having nominally significant causal associations with age-independent/dependent longitudinal changes in HV. In addition, the glycine-to-pyridoxal ratio (mediation proportion: 7.38%) and the phosphate-to-citrate ratio (mediation proportion: 12.55%) mediated the effect of the pathway of L-arginine degradation II on the reduction of age-independent longitudinal changes in HV. Our study reveals the causal effects of GM and BM on longitudinal changes in HV and identifies BM traits with mediating roles. These findings offer valuable insights for the prevention and treatment of the related neuropsychiatric disorders.
海马体体积（HV）的变化与多种神经精神疾病相关。观察性研究表明肠道微生物群（GM）和血液代谢物（BM）与HV变化存在关联；然而，它们之间的因果关系仍不明确。我们旨在使用孟德尔随机化（MR）来研究GM和BM与HV变化之间的因果关联，并探讨BM的潜在中介作用。通过两样本MR（TSMR）分析，我们检查了412个GM特征和1400个BM特征，主要使用逆方差加权法，重点关注它们与HV年龄独立/相关纵向变化的因果关系。此外，我们通过两步MR设计探讨了BM的中介作用。我们确定了44个GM特征和175个BM特征与HV年龄独立/相关纵向变化存在名义上显著的因果关联。此外，甘氨酸与吡哆醛比率（中介比例：7.38%）和磷酸盐与柠檬酸盐比率（中介比例：12.55%）介导了L-精氨酸降解途径II对HV年龄独立纵向变化减少的影响。我们的研究揭示了GM和BM对HV纵向变化的因果效应，并确定了具有中介作用的BM特征。这些发现为相关神经精神疾病的预防和治疗提供了有价值的见解。
