Original Research ARTICLE
Dietary fiber-induced microbial short chain fatty acids suppress ILC2-dependent airway inflammation
- 1Janssen Research and Development, United States
- 2Keck School of Medicine, University of Southern California, United States
- 3Janssen Research and Development, United States
- 4Harbor–UCLA Medical Center, United States
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 also to prevent lung inflammation and asthma.
Keywords: Dietary Fiber, short chain fatty acid (SCFA), ILC2, Airway hyperreactivity, allergic disease
Received: 28 Mar 2019;
Accepted: 14 Aug 2019.
Copyright: © 2019 Lewis, Wang, Shafiei Jahani, Hurrell, Banie, Aleman Muench, Maazi, Howard, Galle-Treger, Lo, Santosh, Baltus, Bongers, San-Mateo, Gilliland, Rehan, Soroosh and Akbari. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. Omid Akbari, Keck School of Medicine, University of Southern California, Los Angeles, 90033, California, United States, email@example.com