View Abstract

A7561 - Dietary Fiber Alters Ozone Induced Airway Hyper Responsiveness in Obese Mice
Author Block: H. Tashiro, D. I. Kasahara, R. S. Osgood, Y. Cho, S. A. Shore; Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
Rationale: Obesity is a risk factor for asthma, especially non-atopic asthma, but obese asthma is difficult to control. In mice, obesity augments pulmonary responses to ozone, a non- atopic asthma trigger, and that obesity-related increases in ozone-induced airway hyperresponsiveness (AHR) require an intact gut microbiome (Cho, Y. et al, AJRCCM 2016; 193:A1077). The data suggest that factors that modify the gut microbiome may be beneficial for obese asthmatics. Dietary fiber has a marked impact on the gut microbiome and fiber-rich diets are beneficial for other obesity-related diseases, including type 2 diabetes. The purpose of this study was to compare the impact of two types of dietary fiber, cellulose and pectin, on ozone-induced AHR in obese mice. Methods: Lean wildtype (WT) and obese db/db mice were fed a pectin-enriched or cellulose-enriched diet for 4 days. Fecal pellets were collected for qPCR-based analysis of the gut microbiome, followed by acute ozone (2 ppm for 3h) or air exposure. 24 h later, airway responsiveness was assessed and bronchoalveor lavage (BAL) was performed. Results: With cellulose treatment, ozone-induced AHR was significantly greater in db/db than WT mice. Compared to cellulose, pectin treatment had no effect on ozone-induced AHR in WT mice, but attenuated ozone-induced AHR in db/db mice. IL-17A contributes to obesity-related increases in ozone-induced AHR and BAL neutrophils (Mathews, J. et al, PMID: 28957638). Consistent with these observations, BAL IL-17 and BAL neutrophils were both significantly lower in pectin-treated than cellulose treated db/db but not WT mice. qPCR analysis of fecal DNA indicated a significant reduction in Firmicutes and a marked increase in γ-Proteobacteria in pectin- versus cellulose-treated db/db mice. Pectin but not cellulose is fermented by gut bacteria yielding short chain fatty acids (SCFA), and serum SCFAs were higher in pectin- versus cellulose-treated mice. However, exogenous administration of the SCFA, propionate, resulted in augmented not attenuated ozone-induced AHR in db/db mice, suggesting that other microbiome-dependent factors must account for the beneficial effect of pectin. Conclusion: Our data indicate that a pectin-rich diet attenuates ozone-induced AHR in obese mice, likely via effects on the production of IL-17A. Our data also suggest that manipulation of dietary fiber may be useful in the treatment of obese asthma.