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

IF 4.8 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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Abstract

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.