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Gut Microbial Tryptophan Metabolism Is Involved in Post-Cardiac Arrest Brain Injury via Pyroptosis Modulation.
Chenghao Wu1,2, Mengyuan Diao3, Shuhang Yu4
1Department of Emergency Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
CNS Neuroscience & Therapeutics
|April 22, 2025
Summary
Eliminating gut microbiota improved survival and neurological outcomes after cardiac arrest in rats. This suggests microbial tryptophan metabolites, specifically kynurenine, play a role in post-cardiac arrest brain injury.
Area of Science:
- Neuroscience
- Microbiology
- Immunology
Background:
- Post-cardiac arrest brain injury (PCABI) is a major cause of mortality and disability.
- The microbiota-gut-brain axis is implicated in neurological disorders, but its role in PCABI is unexplored.
- Microbial tryptophan metabolites are potential mediators in this axis.
Purpose of the Study:
- To investigate the role of microbial tryptophan metabolites in PCABI.
- To explore the microbiota-gut-brain axis connection in PCABI.
Main Methods:
- Rats were pretreated with antibiotics (Abx) to deplete gut microbiota before inducing cardiac arrest/cardiopulmonary resuscitation (CA/CPR).
- Assessed survival rates and neurological outcomes.
- Utilized 16s rDNA sequencing, PICRUSt2, metabolomic profiling, and in vitro/in vivo molecular techniques (qRT-PCR, immunohistochemistry, immunofluorescence).
Main Results:
- Antibiotic treatment improved 24-h survival and neurological function in rats post-CA/CPR.
- Abx altered microbial composition, increasing microbial tryptophan metabolism, particularly via the kynurenine pathway.
- Elevated kynurenine levels in feces, circulation, and brain correlated with upregulated aryl hydrocarbon receptor (AhR) and inhibited NLRP3-induced pyroptosis.
Conclusions:
- The gut microbiota and microbiota-gut-brain axis are crucial in PCABI progression.
- Kynurenine may exert neuroprotective effects by inhibiting NLRP3-induced pyroptosis in PCABI.
- This study highlights kynurenine as a potential therapeutic target for PCABI.
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