Chen Kun, Zhao Qiuyi, Li Shuyuan, Wang Jing, Feng Chao, Wang Longmei, Yan Xiaoyan, Li Ben, Zhao Qian, Qiu Yulan
Department of Toxicology, School of Public Health, Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
Department of Oral Medicine, The Second Hospital of Tangshan, Tangshan, 063000, Hebei, China.
Biol Trace Elem Res. 2025 Aug 19. doi: 10.1007/s12011-025-04783-y.
Arsenic is recognized for its harmful effects on neurodevelopment and cognitive function, and neurodegenerative alterations induced by arsenic exposure may eventually lead to Alzheimer's disease (AD). However, the precise changes in the gut microbiome and tryptophan (Trp) metabolism resulting from arsenic exposure, as well as their role in the "microbiome-tryptophan metabolite-brain axis" in AD, remain poorly understood. In this study, the rats were exposed to arsenic in utero, with continued exposure lasting until 185 days after birth, through free drinking water contaminated with varying concentrations of NaAsO (0, 30 mg/L, and100mg/L). The findings indicated that the arsenic-exposed groups displayed marked neurobehavioral deficits and exhibited typical AD-like pathological alterations. Long-term arsenic exposure led to gut microbiota dysbiosis in the offspring rats, and significant changes were observed in the levels of tryptophan and its metabolites in the hippocampus of the rats. Notably, metabolites within the kynurenine metabolic pathway showed strong correlations with the majority of differential genera in both the control and high arsenic groups. Overall, this study establishes a multimodal association between chronic arsenic exposure, gut microbiota perturbations, tryptophan-kynurenine pathway dysregulation, and AD-like pathology. These findings present a novel perspective for preventing or treating AD.
砷因其对神经发育和认知功能的有害影响而为人所知，砷暴露引起的神经退行性改变最终可能导致阿尔茨海默病（AD）。然而，砷暴露导致的肠道微生物群和色氨酸（Trp）代谢的具体变化，以及它们在AD的“微生物群-色氨酸代谢物-脑轴”中的作用，仍知之甚少。在本研究中，大鼠在子宫内接触砷，并通过饮用含有不同浓度NaAsO（0、30mg/L和100mg/L）的污染自由饮水持续暴露至出生后185天。研究结果表明，砷暴露组表现出明显的神经行为缺陷，并呈现出典型的AD样病理改变。长期砷暴露导致后代大鼠肠道微生物群失调，且大鼠海马中色氨酸及其代谢物水平发生显著变化。值得注意的是，犬尿氨酸代谢途径中的代谢物与对照组和高砷组中的大多数差异属均呈现出强相关性。总体而言，本研究建立了慢性砷暴露、肠道微生物群紊乱、色氨酸-犬尿氨酸途径失调与AD样病理之间的多模式关联。这些发现为预防或治疗AD提供了新的视角。
