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Publications

Journal Article Epublish

PubMed: 40435188 DOI: 10.1371/journal.pone.0324230

The role of gut leakage and immune cell miss-homing on gut dysbiosis-induced lung inflammation in a DSS mice model.

PLoS One 20(5):e0324230

Authors: Mariam Wed Eladham, Narjes Saheb Sharif-Askari, Priyadharshini Sekar, Bushra Mdkhana, Balachandar Selvakumar, Baraa Khalid Salah Al-Sheakly, Fatemeh Saheb Sharif-Askari, Ibrahim Hachim, Rabih Halwani

Affiliations

  • Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
  • Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
  • Department of Pharmacy Practice and Pharmacotherapeutics, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates.
  • Prince Abdullah Ben Khaled Celiac Disease Chair, Department of Pediatrics, Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia.

Abstract

BACKGROUND

Inflammatory Bowel Disease (IBD), encompassing Crohn's disease and ulcerative colitis, affects millions globally, with extraintestinal manifestations (EIMs) occurring in 25-40% of patients. Among these, respiratory complications are of particular concern, yet the immunologic and physiologic mechanisms underlying gut-lung interactions remain poorly understood. The gut-lung axis (GLA) describes bi-directional communication between the gut and lungs, where microbial dysbiosis in the gut can drive lung inflammation and immune dysregulation.

METHODS

Mice were treated with 4% DSS for 7 days to induce colitis. Gut permeability, tight junction protein expression, lung inflammation, immune cell trafficking, and microbial translocation were assessed through histology, qPCR, flow cytometry, and GFP-tagged fecal microbiome experiments.

RESULTS

DSS treatment led to significant disruption of the gut barrier, with upregulation of gut leakage markers and downregulation of tight junction proteins. Lung inflammation was characterized by elevated IL-17, neutrophil infiltration, and airway hyperresponsiveness. Flow cytometry revealed mis-homing of gut-primed immune cells (α4β7+ and CCR9 + CD4+) to the lungs and tracking bacteria via GFP- tagged fecal microbiome confirmed microbial translocation from the gut to the lungs which may contribute to lung inflammation.

CONCLUSION

Disrupted gut integrity facilitates microbial translocation and immune cell mis-homing, contributing to lung inflammation. These results provide new insights into how gut dysbiosis influences respiratory inflammation.

MeSH

Dysbiosis, Cells, Lung, Colitis, Tight Junctions, Tight Junction Proteins