Gut dysbiosis promotes M2 macrophage polarization and allergic airway inflammation via fungi-induced PGE₂.

Journal Article (Journal Article)

Although imbalances in gut microbiota composition, or "dysbiosis," are associated with many diseases, the effects of gut dysbiosis on host systemic physiology are less well characterized. We report that gut dysbiosis induced by antibiotic (Abx) treatment promotes allergic airway inflammation by shifting macrophage polarization in the lung toward the alternatively activated M2 phenotype. Adoptive transfer of alveolar macrophages derived from Abx-treated mice was sufficient to increase allergic airway inflammation. Abx treatment resulted in the overgrowth of a commensal fungal Candida species in the gut and increased plasma concentrations of prostaglandin E₂ (PGE₂), which induced M2 macrophage polarization in the lung. Suppression of PGE₂ synthesis by the cyclooxygenase inhibitors aspirin and celecoxib suppressed M2 macrophage polarization and decreased allergic airway inflammatory cell infiltration in Abx-treated mice. Thus, Abx treatment can cause overgrowth of particular fungal species in the gut and promote M2 macrophage activation at distant sites to influence systemic responses including allergic inflammation.

Full Text

Duke Authors

Cited Authors

  • Kim, Y-G; Udayanga, KGS; Totsuka, N; Weinberg, JB; Núñez, G; Shibuya, A

Published Date

  • January 15, 2014

Published In

Volume / Issue

  • 15 / 1

Start / End Page

  • 95 - 102

PubMed ID

  • 24439901

Pubmed Central ID

  • PMC3957200

Electronic International Standard Serial Number (EISSN)

  • 1934-6069

Digital Object Identifier (DOI)

  • 10.1016/j.chom.2013.12.010


  • eng

Conference Location

  • United States