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Lactobacillus taiwanensis BCRC17755 alleviates motor dysfunction and dopaminergic neuronal loss in mouse models of Parkinson’s disease

于Beneficial Microbes
著者:
Y. Choi Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, South Korea

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https://orcid.org/0009-0002-8071-4558
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J.G. Choi Department of Oriental Pharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, South Korea
Current address: Mthera Pharma Co., 38 Magokjungang 8-ro, Gangseo-gu, Seoul 07793, South Korea

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https://orcid.org/0000-0002-5078-9527
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E. Huh Department of Oriental Pharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, South Korea
Current address: Department of Formulae Pharmacology, College of Korean Medicine, Gachon University, 1342 Seongnamdae-ro, Sujung-Gu, Seongnam 13120, South Korea

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https://orcid.org/0009-0001-1090-1705
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H. Eo Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, South Korea
Current address: Department of Food and Nutrition, Chung-Ang University, Anseong, 17546, South Korea

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https://orcid.org/0000-0002-1532-613X
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Y.-J. Shin Neurobiota Research Center, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, South Korea

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M.G. Park MetaCen Therapeutics Inc. R&D Center, 256 Changnyong-daero, Yeongtong-gu, Suwon 16229, South Korea

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D.-H. Kim Neurobiota Research Center, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, South Korea

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M.S. Oh Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, South Korea
Department of Oriental Pharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, South Korea
Neurobiota Research Center, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, South Korea

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https://orcid.org/0000-0001-8189-4066
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Abstract

Parkinson’s disease (PD) is a complex progressive neurodegenerative disease characterized by both motor and nonmotor symptoms such as constipation and dyspepsia. Recently, growing evidence has suggested that a specific gut microbiome is associated with the pathophysiology of PD through the microbiota-gut-brain axis. We previously discovered that Proteus mirabilis induced motor impairment and brain dopaminergic neurodegeneration in normal mice. In this context, exploring beneficial microbe would be reasonable strategy to treat PD fundamentally. With that the current study aimed to evaluate whether Lactobacillus taiwanensis BCRC17755 (BCRC17755) could ameliorate PD pathologies induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and P. mirabilis in mice. To demonstrate this, we measured motor function by performing pole test and the rotarod test and conducted histological analysis to assess the changes of factors in both brain and the gut. As a result, BCRC17755 decreased faecal abundance of P. mirabilis, which was higher in both the MPTP and P. mirabilis-treated mice. Additionally, BCRC17755 improved the motor deficits and alleviated damage to nigrostriatal dopaminergic neurons observed in both MPTP and P. mirabilis-induced PD mice. Furthermore, BCRC17755 mitigated microglial hyperactivation triggered by MPTP and P. mirabilis in the substantia nigra pars compacta and striatum of mice. Similarly, the release of inflammatory cytokines, including interleukin-1 beta and tumor necrosis factor alpha, was suppressed following the administration of BCRC17755 in the colon. Taken together, all the results suggest that BCRC17755 is a beneficial microbe for the treatment of PD by inhibiting the P. mirabilis growth.

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