AUTHOR=Chen Yuhua , Chen Junhui , Wei Hong , Gong Kai , Meng Jiao , Long Tianlin , Guo Jianfeng , Hong Jun , Yang Lingjian , Qiu Junling , Xiong Kun , Wang Zhanxiang , Xu Quanhua 

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

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1172710

DOI=10.3389/fimmu.2023.1172710

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>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.</p></sec><sec><title>Objectives</title><p>This study investigated the association between PGAM5 and gut microbiota in mice with TBI.</p></sec><sec><title>Methods</title><p>The controlled cortical impact injury was established in mice with genetically-ablated <italic>Pgam5</italic> (<italic>Pgam5<sup>−/−</sup></italic>) or wild type, and WT male mice were treated with fecal microbiota transplantation (FMT) from male <italic>Pgam5<sup>−/−</sup></italic> mice or <italic>Akkermansia muciniphila</italic> (<italic>A. muciniphila</italic>). Then the gut microbiota abundance, blood metabolites, neurological function, and nerve injury were detected.</p></sec><sec><title>Results</title><p>Treated with antibiotics for suppressing gut microbiota in <italic>Pgam5<sup>−/−</sup></italic> mice partially relieved the role of <italic>Pgam5</italic> deficiency in the improvement of initial inflammatory factors and motor dysfunction post-TBI. <italic>Pgam5</italic> knockout exhibited an increased abundance of <italic>A. muciniphila</italic> in mice. FMT from male <italic>Pgam5<sup>−/−</sup></italic> 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 <italic>A. muciniphila</italic> was negatively associated with intestinal mucosal injury and neuroinflammation post-TBI. Moreover, <italic>A. muciniphila</italic> treatment ameliorated neuroinflammation and nerve injury by regulating Nlrp3 inflammasome activation in cerebral cortex with TBI.</p></sec><sec><title>Conclusion</title><p>Thus, the present study provides evidence that Pgam5 is involved in gut microbiota-mediated neuroinflammation and nerve injury, with <italic>A. muciniphila</italic>-Nlrp3 contributing to peripheral effects.</p></sec>