AUTHOR=Lewis Gavin , Wang Bowen , Shafiei Jahani Pedram , Hurrell Benjamin P. , Banie Homayon , Aleman Muench German R. , Maazi Hadi , Helou Doumet Georges , Howard Emily , Galle-Treger Lauriane , Lo Richard , Santosh Swetha , Baltus Andrew , Bongers Gerrold , San-Mateo Lani , Gilliland Frank D. , Rehan Virender K. , Soroosh Pejman , Akbari Omid TITLE=Dietary Fiber-Induced Microbial Short Chain Fatty Acids Suppress ILC2-Dependent Airway Inflammation JOURNAL=Frontiers in Immunology VOLUME=10 YEAR=2019 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.02051 DOI=10.3389/fimmu.2019.02051 ISSN=1664-3224 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.