Dietary Fiber-Induced Microbial Short Chain Fatty Acids Suppress ILC2-Dependent Airway Inflammation

Gavin Lewis, Bowen Wang, Pedram Shafiei Jahani, Benjamin P. Hurrell, Homayon Banie, German R. Aleman Muench, Hadi Maazi, Doumet Georges Helou, Emily Howard, Lauriane Galle-Treger, Richard Lo, Swetha Santosh, Andrew Baltus, Gerrold Bongers, Lani San-Mateo, Frank D. Gilliland, Virender K. Rehan, Pejman Soroosh, Omid Akbari

Research output: Contribution to journalArticlepeer-review

97 Scopus citations

Abstract

Group 2 Innate lymphoid cells (ILC2) contribute significantly to allergic inflammation. However, the role of microbiota on ILC2s remains to be unraveled. Here we show that short chain fatty acids (SCFAs), such as butyrate, derived from fermentation of dietary fibers by the gut microbiota inhibit pulmonary ILC2 functions and subsequent development of airway hyperreactivity (AHR). We further show that SCFAs modulate GATA3, oxidative phosphorylation, and glycolytic metabolic pathways in pulmonary ILC2s. The observed phenotype is associated with increased IL-17a secretion by lung ILC2s and linked to enhanced neutrophil recruitment to the airways. Finally, we show that butyrate-producing gut bacteria in germ-free mice effectively suppress ILC2-driven AHR. Collectively, our results demonstrate a previously unrecognized role for microbial-derived SCFAs on pulmonary ILC2s in the context of AHR. The data suggest strategies aimed at modulating metabolomics and microbiota in the gut, not only to treat, but to prevent lung inflammation and asthma.

Original languageEnglish
Article number2051
JournalFrontiers in Immunology
Volume10
DOIs
StatePublished - 18 Sep 2019
Externally publishedYes

Keywords

  • ILC2
  • airway hyperreactivity
  • allergic disease
  • dietary fiber
  • short chain fatty acid

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