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Related Experiment Videos

Yuhua Chen1,2,3,4, Junhui Chen1, Hong Wei2,5

  • 1Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha, Hunan, China.

Frontiers in Immunology
|June 8, 2023
PubMed
Summary

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Phosphoglycerate mutase 5 (PGAM5) influences the gut microbiome

Area of Science:

  • Neuroscience
  • Microbiology
  • Metabolism

Background:

  • The gut-brain axis plays a crucial role in managing chronic traumatic encephalopathy (CTE) after traumatic brain injury (TBI).
  • Mitochondrial protein Phosphoglycerate mutase 5 (PGAM5) regulates mitochondrial homeostasis and is implicated in mediating the intestinal barrier and gut microbiome.
  • Understanding the interplay between PGAM5, the gut microbiome, and TBI is essential for developing novel therapeutic strategies.

Purpose of the Study:

  • To investigate the association between PGAM5 and the gut microbiota in a mouse model of TBI.
  • To elucidate the role of PGAM5 in modulating gut microbiota composition and its subsequent impact on neuroinflammation and neurological deficits post-TBI.

Main Methods:

  • Establishment of controlled cortical impact injury in wild-type (WT) and Pgam5 knockout (Pgam5-/-) mice.
Keywords:
Akkermansia muciniphilaNlrp3Pgam5TBIgut-microbiota-brain axisneuroprotection

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  • Fecal microbiota transplantation (FMT) from Pgam5-/- mice or administration of Akkermansia muciniphila (A. muciniphila) to WT mice with TBI.
  • Assessment of gut microbiota abundance, blood metabolites, neurological function, and nerve injury.

    • Main Results:

    • Pgam5 deficiency and FMT from Pgam5-/- mice improved motor function and reduced neuroinflammation post-TBI, partly mediated by gut microbiota.
    • Pgam5 knockout led to an increased abundance of A. muciniphila, which was negatively associated with intestinal mucosal injury and neuroinflammation.
    • A. muciniphila treatment ameliorated neuroinflammation and nerve injury by regulating Nlrp3 inflammasome activation in the cerebral cortex.

    Conclusions:

    • PGAM5 is involved in gut microbiota-mediated neuroinflammation and nerve injury following TBI.
    • Akkermansia muciniphila plays a significant role in the protective effects observed, potentially through Nlrp3 inflammasome modulation.
    • Targeting the PGAM5-gut microbiota axis, particularly A. muciniphila, presents a promising therapeutic avenue for TBI and related neurodegenerative conditions.