Gut Dysbiosis Promotes M2 Macrophage Polarization and Allergic Airway Inflammation via Fungi-Induced PGE2
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 shif...
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Published in | Cell host & microbe Vol. 15; no. 1; pp. 95 - 102 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Elsevier Inc
15.01.2014
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Online Access | Get full text |
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Summary: | 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.
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•Antibiotic treatment induced gut fungal overgrowth•Gut fungal overgrowth promoted allergic airway inflammation•Gut fungal overgrowth elevated plasma PGE2 that promoted M2 macrophage polarization•M2 macrophage was involved in allergic airway inflammation
Antibiotic treatment induces dysbiosis. The effects of dysbiosis on host physiology are just emerging. Kim et al. find that antibiotic treatment of mice facilitates overgrowth of a gut commensal Candida species, which increases plasma concentration of prostaglandin E2. Fungi-induced prostaglandin E2 in turn promotes M2 macrophage activation and thus exacerbates allergic airway inflammation. |
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ISSN: | 1931-3128 1934-6069 |
DOI: | 10.1016/j.chom.2013.12.010 |