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Microbiota contribute to obesity-related increases in the pulmonary response to ozone.

Abstract

RATIONALE

Obesity is a risk factor for asthma, especially non-atopic asthma, and attenuates the efficacy of standard asthma therapeutics. Obesity also augments pulmonary responses to ozone, a non-atopic asthma trigger.

OBJECTIVES

The purpose of this study was to determine whether obesity-related alterations in gut microbiota contribute to these augmented responses to ozone.

METHODS

Obese db/db mice were treated with a cocktail of antibiotics, or fed diets rich in pectin or cellulose prior to ozone exposure. Airway responsiveness was assessed 24 hours after exposure. In addition, germ free mice were gavaged with colonic contents from obese or lean mice two weeks prior to exposure and evaluation.

MEASUREMENTS AND MAIN RESULTS

Ozone-induced increases in airway responsiveness, a canonical feature of asthma, were greater in db/db mice than in lean controls. Depletion of gut microbiota with a cocktail of antibiotics attenuated obesity-related increases in the response to ozone, indicating a role for microbiota. Moreover, ozone-induced airway hyperresponsiveness was greater in germ free mice that had been reconstituted with colonic contents of db/db versus wildtype mice. In addition, compared to dietary supplementation with the non-fermentable fiber, cellulose, dietary supplementation with the fermentable fiber, pectin, attenuated obesity-related increases in the pulmonary response to ozone, likely by reducing ozone-induced release of IL-17A.

CONCLUSIONS

Our data indicate a role for microbiota in obesity-related increases in the response to an asthma trigger, and suggest that microbiome-based therapies such as prebiotics may provide an alternative therapeutic strategy for obese asthmatic patients.

Authors+Show Affiliations

Harvard University T H Chan School of Public Health, 1857, Department of Environmental Health, Boston, Massachusetts, United States.Harvard University T H Chan School of Public Health, 1857, Department of Environmental Health, Boston, Massachusetts, United States.Harvard University T H Chan School of Public Health, 1857, Department of Environmental Health, Boston, Massachusetts, United States.Harvard University T H Chan School of Public Health, 1857, Department of Environmental Health, Boston, Massachusetts, United States.Brigham and Women's Hospital, 1861, Massachusetts Host Microbiome Center, Boston, Massachusetts, United States.Brigham and Women's Hospital, 1861, Massachusetts Host Microbiome Center, Boston, Massachusetts, United States.Harvard University T H Chan School of Public Health, 1857, Department of Biostatistics, Boston, Massachusetts, United States.Harvard University T H Chan School of Public Health, 1857, Department of Biostatistics, Boston, Massachusetts, United States.Harvard University T H Chan School of Public Health, 1857, Department of Environmental Health, Boston, Massachusetts, United States ; sshore@hsph.harvard.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31144984

Citation

Tashiro, Hiroki, et al. "Microbiota Contribute to Obesity-related Increases in the Pulmonary Response to Ozone." American Journal of Respiratory Cell and Molecular Biology, 2019.
Tashiro H, Cho Y, Kasahara DI, et al. Microbiota contribute to obesity-related increases in the pulmonary response to ozone. Am J Respir Cell Mol Biol. 2019.
Tashiro, H., Cho, Y., Kasahara, D. I., Brand, J. D., Bry, L., Yeliseyev, V., ... Shore, S. A. (2019). Microbiota contribute to obesity-related increases in the pulmonary response to ozone. American Journal of Respiratory Cell and Molecular Biology, doi:10.1165/rcmb.2019-0144OC.
Tashiro H, et al. Microbiota Contribute to Obesity-related Increases in the Pulmonary Response to Ozone. Am J Respir Cell Mol Biol. 2019 May 30; PubMed PMID: 31144984.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Microbiota contribute to obesity-related increases in the pulmonary response to ozone. AU - Tashiro,Hiroki, AU - Cho,Youngji, AU - Kasahara,David I, AU - Brand,Jeffrey D, AU - Bry,Lynn, AU - Yeliseyev,Vladimir, AU - Abu-Ali,Galeb, AU - Huttenhower,Curtis, AU - Shore,Stephanie A, Y1 - 2019/05/30/ PY - 2019/5/31/entrez KW - microbiome , airway responsiveness , neutrophil , dietary fiber , IL-17A JF - American journal of respiratory cell and molecular biology JO - Am. J. Respir. Cell Mol. Biol. N2 - RATIONALE: Obesity is a risk factor for asthma, especially non-atopic asthma, and attenuates the efficacy of standard asthma therapeutics. Obesity also augments pulmonary responses to ozone, a non-atopic asthma trigger. OBJECTIVES: The purpose of this study was to determine whether obesity-related alterations in gut microbiota contribute to these augmented responses to ozone. METHODS: Obese db/db mice were treated with a cocktail of antibiotics, or fed diets rich in pectin or cellulose prior to ozone exposure. Airway responsiveness was assessed 24 hours after exposure. In addition, germ free mice were gavaged with colonic contents from obese or lean mice two weeks prior to exposure and evaluation. MEASUREMENTS AND MAIN RESULTS: Ozone-induced increases in airway responsiveness, a canonical feature of asthma, were greater in db/db mice than in lean controls. Depletion of gut microbiota with a cocktail of antibiotics attenuated obesity-related increases in the response to ozone, indicating a role for microbiota. Moreover, ozone-induced airway hyperresponsiveness was greater in germ free mice that had been reconstituted with colonic contents of db/db versus wildtype mice. In addition, compared to dietary supplementation with the non-fermentable fiber, cellulose, dietary supplementation with the fermentable fiber, pectin, attenuated obesity-related increases in the pulmonary response to ozone, likely by reducing ozone-induced release of IL-17A. CONCLUSIONS: Our data indicate a role for microbiota in obesity-related increases in the response to an asthma trigger, and suggest that microbiome-based therapies such as prebiotics may provide an alternative therapeutic strategy for obese asthmatic patients. SN - 1535-4989 UR - https://www.unboundmedicine.com/medline/citation/31144984/Microbiota_contribute_to_obesity_related_increases_in_the_pulmonary_response_to_ozone_ L2 - http://www.atsjournals.org/doi/full/10.1165/rcmb.2019-0144OC?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -