Healthy Human Fecal Microbiota Transplantation into Mice Attenuates MPTP-Induced Neurotoxicity via AMPK/SOD2 Pathway

dc.creatorXie, Zhencao
dc.creatorZhang, Mahui
dc.creatorLuo, Yuqi
dc.creatorJin, Dana
dc.creatorGuo, Xingfang
dc.creatorYang, Wanlin
dc.creatorZheng, Jialing
dc.creatorZhang, Hongfei
dc.creatorZhang, Lu
dc.creatorDeng, Chao
dc.creatorZheng, Wenhua
dc.creatorTan, Eng-King
dc.creatorJin, Kunlin
dc.creatorZhu, Shuzhen
dc.creatorWang, Qing
dc.creator.orcid0000-0002-1336-348X (Jin, Kunlin)
dc.description.abstractIncreasing evidence has shown that gut dysbacteriosis may play a crucial role in neuroinflammation in Parkinson's disease (PD). However, the specific mechanisms that link gut microbiota to PD remain unexplored. Given the critical roles of blood-brain barrier (BBB) dysfunction and mitochondrial dysfunction in the development of PD, we aimed to evaluate the interactions among the gut microbiota, BBB, and mitochondrial resistance to oxidation and inflammation in PD. We investigated the effects of fecal microbiota transplantation (FMT) on the physiopathology of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. The aim was to explore the role of fecal microbiota from PD patients and healthy human controls in neuroinflammation, BBB components, and mitochondrial antioxidative capacity via the AMPK/SOD2 pathway. Compared to control mice, MPTP-treated mice exhibited elevated levels of Desulfovibrio, whereas mice given FMT from PD patients exhibited enriched levels of Akkermansia and mice given FMT from healthy humans showed no significant alterations in gut microbiota. Strikingly, FMT from PD patients to MPTP-treated mice significantly aggravated motor impairments, dopaminergic neurodegeneration, nigrostriatal glial activation and colonic inflammation, and inhibited the AMPK/SOD2 signaling pathway. However, FMT from healthy human controls greatly improved the aforementioned MPTP-caused effects. Surprisingly, the MPTP-treated mice displayed a significant loss in nigrostriatal pericytes, which was restored by FMT from healthy human controls. Our findings demonstrate that FMT from healthy human controls can correct gut dysbacteriosis and ameliorate neurodegeneration in the MPTP-induced PD mouse model by suppressing microgliosis and astrogliosis, ameliorating mitochondrial impairments via the AMPK/SOD2 pathway, and restoring the loss of nigrostriatal pericytes and BBB integrity. These findings raise the possibility that the alteration in the human gut microbiota may be a risk factor for PD and provide evidence for potential application of FMT in PD preclinical treatment.
dc.description.sponsorshipThe authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (NO: 81873777, 82071414), Scientific Research Foundation of Guangzhou (NO: 202206010005) and Science and Technology Program of Guangdong of China (NO: 2020 A0505100037) to QW, and National Natural Science Foundation of China (NO: 82171253), Scientific Research Foundation of Guangdong (NO: 2022A1515 010522) to SZZ.
dc.identifier.citationXie, Z., Zhang, M., Luo, Y., Jin, D., Guo, X., Yang, W., Zheng, J., Zhang, H., Zhang, L., Deng, C., Zheng, W., Tan, E. K., Jin, K., Zhu, S., & Wang, Q. (2023). Healthy Human Fecal Microbiota Transplantation into Mice Attenuates MPTP-Induced Neurotoxicity via AMPK/SOD2 Pathway. Aging and disease, 14(6), 2193–2214. Advance online publication.
dc.publisherAging and Disease
dc.rights.holder© 2023 Xie Z. et al.
dc.rights.licenseAttribution 4.0 International
dc.sourceAging and Disease
dc.subjectParkinson's disease
dc.subjectgut microbiota
dc.subjectfecal microbiota transplantation
dc.titleHealthy Human Fecal Microbiota Transplantation into Mice Attenuates MPTP-Induced Neurotoxicity via AMPK/SOD2 Pathway


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