2. Academic Validation
  3. Gut microbiota from voluntary exercised mice protects the intestinal barrier by inhibiting neutrophil extracellular trap formation

Gut microbiota from voluntary exercised mice protects the intestinal barrier by inhibiting neutrophil extracellular trap formation

  • iScience. 2025 May 27;28(6):112763. doi: 10.1016/j.isci.2025.112763.
Beibei Zhu 1 2,  Hao Wu 3,  Han Zhang 1 2,  Qi Song 1 2,  Yong Xiao 1 2,  Baoping Yu 1 2
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.
  • 2 Key Laboratory of Hubei Province for Digestive System Diseases, Wuhan, Hubei 430060, China.
  • 3 Department of Radiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, China.
PMID: 40585508 DOI: 10.1016/j.isci.2025.112763
Abstract

Ulcerative colitis is an inflammatory bowel disease characterized by impaired intestinal barrier function, dysregulated immune responses, and alterations in the gut microbiota. Excessive formation of neutrophil extracellular traps (NETs), driven by peptidyl arginine deiminase 4 (PAD4) activity, contributes to inflammation modulated by the gut microbiota. In this study, we used a mouse model of dextran sulfate sodium-induced colitis to investigate the effects of voluntary exercise and its underlying mechanisms. Exercise preconditioning attenuated colitis severity, maintained intestinal barrier integrity, normalized gut microbiota composition, and suppressed NET formation. PAD4 inhibition further enhanced these effects. By contrast, the depletion of the gut microbiota by Antibiotics largely abolished the benefits of exercise. Additionally, fecal microbiota transplantation from exercised mice recapitulated these protective effects. These findings elucidate the interplay among exercise, gut microbiota, and PAD4-mediated NET formation. Targeting these pathways may offer promising therapeutic strategies for colitis.

Keywords

Immunology; Microbiome.

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