Akkermansia muciniphila -Nlrp3 is involved in the neuroprotection of phosphoglycerate mutase 5 deficiency in traumatic brain injury mice.

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.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Chen, Chen, Wei, Gong, Meng, Long, Guo, Hong, Yang, Qiu, Xiong, Wang and Xu.)