嗜muciniphila通过调节丁酸盐抑制小胶质细胞介导的神经炎症来保护多巴胺神经毒性

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology Pub Date : 2025-03-07 DOI:10.1016/j.intimp.2025.114374

Kaifei Xu , Guoqing Wang , Jiantao Gong, Xinxing Yang, Yufeng Cheng, Daidi Li, Shuo Sheng, Feng Zhang

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引用次数: 0

摘要

帕金森病（PD）是一种与年龄相关的第二常见的神经退行性疾病。迄今为止，缺乏安全有效的治疗药物。近年来，肠道菌群与中枢神经系统的关系受到越来越多的关注。肠道微生物群的稳态失衡被发现参与PD的进展。本研究通过16S rRNA扩增子测序发现PD大鼠粪便中嗜muciniphila （A. muciniphila）明显减少。此外，我们发现外源性补充嗜粘单胞杆菌可以改善PD大鼠6- ohda诱导的运动功能障碍、多巴胺（DA）神经元损伤和神经炎症因子释放。此外，短链脂肪酸（SCFAs）测序表明，添加A. muciniphila增加了肠道和大脑中的丁酸盐含量。随后的功能实验证实，外源性补充丁酸盐对DA神经毒性具有神经保护作用。机械上，丁酸盐通过抑制小胶质细胞的激活和神经炎症因子的产生来靶向小胶质细胞减轻DA神经元损伤。综上所述，嗜粘单胞菌通过调节丁酸盐抑制小胶质细胞引起的神经炎症来保护DA神经元损伤。这些发现为嗜粘液芽孢杆菌在PD治疗中的潜在应用提供了依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Akkermansia muciniphila protects against dopamine neurotoxicity by modulating butyrate to inhibit microglia-mediated neuroinflammation

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Akkermansia muciniphila protects against dopamine neurotoxicity by modulating butyrate to inhibit microglia-mediated neuroinflammation

Parkinson's disease (PD) is an age-related and second most common neurodegenerative disease. To date, safe and efficient therapeutic drugs are deficient. In recent years, the relationship between gut microbiota and CNS have received more attention. Homeostatic imbalance of gut microbiota was revealed to participate in the progression of PD. This study detected that Akkermansia muciniphila (A. muciniphila) was apparently decreased in the feces of PD rats via 16S rRNA amplicon sequencing. Furtherly, we found that exogenous supplementation of A. muciniphila could improve 6-OHDA-induced motor dysfunction and dopamine (DA) neuronal damage and neuroinflammatory factors release in PD rats. Moreover, the short-chain fatty acids (SCFAs) sequencing demonstrated that A. muciniphila addition increased butyrate content both in gut and brain. The subsequent functional experiments confirmed that the exogenous supplementation of butyrate conferred neuroprotection against DA neurotoxicity. Mechanically, butyrate targeted microglia to attenuate DA neuronal injury via inhibiting microglia activation and neuroinflammatory factors production. In conclusion, A. muciniphila protected DA neuronal damage by modulating butyrate to inhibit microglia-elicited neuroinflammation. These findings provided a potential application of A. muciniphila on PD treatment.

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.