Engineering and Technology Research Center of Traditional Chinese Veterinary Medicine of Gansu Province, Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China.
Engineering and Technology Research Center of Traditional Chinese Veterinary Medicine of Gansu Province, Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China.
Biomed Pharmacother. 2020 Jul;127:110150. doi: 10.1016/j.biopha.2020.110150. Epub 2020 Apr 21.
Among all types of pollution, heavy metals are considered the greatest threat to human health, and heavy metals are associated with an increased risk of cardiovascular disease, coronary heart disease and neurodegenerative disorders. Manganese (Mn) exposure is well reported to exert neurotoxicity and various neurodegenerative disorders, but the mechanisms are not clear. The gut microbiota plays a crucial role in the bidirectional gut-brain axis that integrates the gut and central nervous system (CNS) activities. The changes in chemical signaling, metabolism and gut microbiota associated with Mn exposure have provided deeper insight into the neurotoxic mechanism of Mn. We observed that Mn exposure increases host manganic bioaccumulation, and β-amyloid (Aβ), receptor-interacting protein kinase 3 (RIP3) and caspase-3 production in the brain, and causes hippocampal degeneration and necrosis. Mn exposure led to decreased gut bacterial richness, especially for Prevotellaceae, Fusobacteriaceae and Lactobacillaceae. In addition, Mn exposure altered the metabolism of tryptamine, taurodeoxycholic acid, β-hydroxypyruvic acid and urocanic acid. Meanwhile, we found correlations between the abundance of certain bacterial species and the level of tryptamine, taurodeoxycholic acid, β-hydroxypyruvic acid and urocanic acid. Fecal microbiome transplantation from normal rats could alleviate the neurotoxicity of Mn exposure by shaping the gut microbiota. Our findings highlight the role of gut dysbiosis-promoted neurotoxicity in Mn exposure and suggest a novel therapeutic strategy of remodeling the gut microbiota.
在所有类型的污染中，重金属被认为对人类健康危害最大，重金属与心血管疾病、冠心病和神经退行性疾病的风险增加有关。锰（Mn）暴露被充分报道会产生神经毒性和各种神经退行性疾病，但机制尚不清楚。肠道微生物群在双向肠-脑轴中起着至关重要的作用，该轴整合了肠道和中枢神经系统（CNS）的活动。与 Mn 暴露相关的化学信号、代谢和肠道微生物群的变化为 Mn 的神经毒性机制提供了更深入的了解。我们观察到 Mn 暴露会增加宿主的锰生物积累，以及大脑中的β-淀粉样蛋白（Aβ）、受体相互作用蛋白激酶 3（RIP3）和半胱天冬酶-3的产生，并导致海马体退化和坏死。Mn 暴露导致肠道细菌丰富度降低，特别是普雷沃氏菌科、梭杆菌科和乳杆菌科。此外，Mn 暴露改变了色胺、牛磺脱氧胆酸、β-羟丙酮酸和尿刊酸的代谢。同时，我们发现某些细菌物种的丰度与色胺、牛磺脱氧胆酸、β-羟丙酮酸和尿刊酸的水平之间存在相关性。来自正常大鼠的粪便微生物群移植可以通过塑造肠道微生物群来缓解 Mn 暴露的神经毒性。我们的研究结果强调了肠道微生物失调促进 Mn 暴露神经毒性的作用，并提出了一种重塑肠道微生物群的新治疗策略。
