2. Academic Validation
  3. Effect of chronic intermittent hypoxia on apoptosis based on microbiome-based co-metabolomics

Effect of chronic intermittent hypoxia on apoptosis based on microbiome-based co-metabolomics

  • Exp Neurol. 2026 Jul:401:115726. doi: 10.1016/j.expneurol.2026.115726.
Tingyuan Zeng 1,  Cheng Niu 1,  Jianqin Cheng 2,  Yu Pan 2,  Jiaxin Lu 3,  Min Wu 4,  Wen Li 4,  Yaqin Liu 4,  Dan Zhao 5
Affiliations

Affiliations

  • 1 Guizhou University Medical College, Guiyang 550025, Guizhou Province, China.
  • 2 Zunyi Medical University, 563000, Guizhou Province, China.
  • 3 Guizhou University of Traditional Chinese Medicine, 550002, Guizhou Province, China.
  • 4 Department of Sleep Medicine, Guizhou Provincial People's Hospital, 550002, Guizhou Province,China.
  • 5 Department of Sleep Medicine, Guizhou Provincial People's Hospital, 550002, Guizhou Province,China. Electronic address: [email protected].
PMID: 41825556 DOI: 10.1016/j.expneurol.2026.115726
Abstract

Background: Obstructive sleep apnea (OSA) is linked to metabolic dysfunction, but the role of chronic intermittent hypoxia (CIH)-induced mitochondrial Apoptosis remains unclear. This study investigated whether CIH-induced lung Apoptosis involves gut microbiota and metabolite changes.

Methods: Mice exposed to CIH were analyzed using 16S rRNA Sequencing and GC-MS metabolomics. Apoptosis markers (Drp1, Bax, Bcl-2, Caspase-3) were assessed via Western blot, immunohistochemistry, TUNEL, and electron microscopy.

Results: (1) CIH disrupted fatty acid metabolism (e.g., decreased arachidonic acid, increased nervonic acid), reversible with Mdivi-1 (mitochondrial fission inhibitor). (2) CIH altered gut microbiota, partially restored by Mdivi-1. (3) KEGG analysis revealed Apoptosis, Autophagy, and P53 pathway changes. (4) CIH reduced mouse weight and cognitive performance; Mdivi-1 improved these. (5) CIH increased Bax/Caspase-3 and decreased Bcl-2, worsening mitochondrial damage-exacerbated by CCCP (Apoptosis Inducer) but mitigated by Mdivi-1.

Conclusions: Mdivi-1 alleviated CIH-induced gut dysbiosis, Apoptosis, and mitochondrial damage, while CCCP worsened these effects. Gut microbiota and metabolic changes may mediate CIH-induced lung Apoptosis.

Keywords

Chronic intermittent hypoxia; Intestinal flora; Mitochondrial apoptosis; Targeted metabolomics.

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