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- Title
Akkermansia muciniphila-Nlrp3 is involved in the neuroprotection of phosphoglycerate mutase 5 deficiency in traumatic brain injury mice.
- Authors
Yuhua Chen; Junhui Chen; Hong Wei; Kai Gong; Jiao Meng; Tianlin Long; Jianfeng Guo; Jun Hong; Lingjian Yang; Junling Qiu; Kun Xiong; Zhanxiang Wang; Quanhua Xu
- Abstract
Introduction: Gut-microbiota-brain axis is a potential treatment to decrease the risk of chronic traumatic encephalopathy following traumatic brain injury (TBI). Phosphoglycerate mutase 5 (PGAM5), a mitochondrial serine/threonine protein phosphatase, resides in mitochondrial membrane and regulates mitochondrial homeostasis and metabolism. Mitochondria mediates intestinal barrier and gut microbiome. Objectives: This study investigated the association between PGAM5 and gut microbiota in mice with TBI. Methods: The controlled cortical impact injury was established in mice with genetically-ablated Pgam5 (Pgam5-/-) or wild type, and WT male mice were treated with fecal microbiota transplantation (FMT) from male Pgam5-/-mice or Akkermansia muciniphila (A. muciniphila). Then the gut microbiota abundance, blood metabolites, neurological function, and nerve injury were detected. Results: Treated with antibiotics for suppressing gut microbiota in Pgam5-/-mice partially relieved the role of Pgam5 deficiency in the improvement of initial inflammatory factors and motor dysfunction post-TBI. Pgam5 knockout exhibited an increased abundance of A. muciniphila in mice. FMT from male Pgam5-/-mice enabled better maintenance of amino acid metabolism and peripherial environment than that in TBI-vehicle mice, which suppressed neuroinflammation and improved neurological deficits, and A. muciniphila was negatively associated with intestinal mucosal injury and neuroinflammation post-TBI.Moreover, A.muciniphila treatment ameliorated neuroinflammation and nerve injury by regulating Nlrp3 inflammasome activation in cerebral cortex with TBI. Conclusion: Thus, the present study provides evidence that Pgam5 is involved in gut microbiota-mediated neuroinflammation and nerve injury, with A. muciniphila-Nlrp3 contributing to peripheral effects.
- Subjects
BRAIN injuries; CHRONIC traumatic encephalopathy; FECAL microbiota transplantation; AMINO acid metabolism; PHOSPHOPROTEIN phosphatases
- Publication
Frontiers in Immunology, 2023, p1
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2023.1172710