Microbiota Contribute to Obesity-related Increases in the Pulmonary Response to Ozone

Overview

Journal Am J Respir Cell Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2019 May 31

PMID 31144984

Citations 24

Authors

Hiroki Tashiro

Youngji Cho

David I Kasahara

Jeffrey D Brand

Lynn Bry

Vladimir Yeliseyev

Galeb Abu-Ali

Curtis Huttenhower

Stephanie A Shore

Affiliations

Soon will be listed here.

Abstract

Obesity is a risk factor for asthma, especially nonatopic asthma, and attenuates the efficacy of standard asthma therapeutics. Obesity also augments pulmonary responses to ozone, a nonatopic asthma trigger. The purpose of this study was to determine whether obesity-related alterations in gut microbiota contribute to these augmented responses to ozone. Ozone-induced increases in airway responsiveness, a canonical feature of asthma, were greater in obese mice than in lean wild-type control mice. 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 than in wild-type mice. In addition, compared with dietary supplementation with the nonfermentable 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. 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 patients with asthma.

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References

Henao-Mejia J, Elinav E, Jin C, Hao L, Mehal W, Strowig T . Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature. 2012; 482(7384):179-85. PMC: 3276682. DOI: 10.1038/nature10809. View

Ridaura V, Faith J, Rey F, Cheng J, Duncan A, Kau A . Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science. 2013; 341(6150):1241214. PMC: 3829625. DOI: 10.1126/science.1241214. View

Miyamoto J, Watanabe K, Taira S, Kasubuchi M, Li X, Irie J . Barley β-glucan improves metabolic condition via short-chain fatty acids produced by gut microbial fermentation in high fat diet fed mice. PLoS One. 2018; 13(4):e0196579. PMC: 5919537. DOI: 10.1371/journal.pone.0196579. View

Drew J, Reichardt N, Williams L, Mayer C, Walker A, Farquharson A . Dietary fibers inhibit obesity in mice, but host responses in the cecum and liver appear unrelated to fiber-specific changes in cecal bacterial taxonomic composition. Sci Rep. 2018; 8(1):15566. PMC: 6197265. DOI: 10.1038/s41598-018-34081-8. View

Shore S, Rivera-Sanchez Y, Schwartzman I, Johnston R . Responses to ozone are increased in obese mice. J Appl Physiol (1985). 2003; 95(3):938-45. DOI: 10.1152/japplphysiol.00336.2003. View

Cani P, Bibiloni R, Knauf C, Waget A, Neyrinck A, Delzenne N . Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes. 2008; 57(6):1470-81. DOI: 10.2337/db07-1403. View

Mathews J, Krishnamoorthy N, Kasahara D, Cho Y, Wurmbrand A, Ribeiro L . IL-33 Drives Augmented Responses to Ozone in Obese Mice. Environ Health Perspect. 2016; 125(2):246-253. PMC: 5289908. DOI: 10.1289/EHP272. View

Turnbaugh P, Ley R, Mahowald M, Magrini V, Mardis E, Gordon J . An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006; 444(7122):1027-31. DOI: 10.1038/nature05414. View

Schatz M, Hsu J, Zeiger R, Chen W, Dorenbaum A, Chipps B . Phenotypes determined by cluster analysis in severe or difficult-to-treat asthma. J Allergy Clin Immunol. 2013; 133(6):1549-56. DOI: 10.1016/j.jaci.2013.10.006. View

10.

Dixon A, Pratley R, Forgione P, Kaminsky D, Whittaker-Leclair L, Griffes L . Effects of obesity and bariatric surgery on airway hyperresponsiveness, asthma control, and inflammation. J Allergy Clin Immunol. 2011; 128(3):508-15.e1-2. PMC: 3164923. DOI: 10.1016/j.jaci.2011.06.009. View

11.

Ubeda C, Taur Y, Jenq R, Equinda M, Son T, Samstein M . Vancomycin-resistant Enterococcus domination of intestinal microbiota is enabled by antibiotic treatment in mice and precedes bloodstream invasion in humans. J Clin Invest. 2010; 120(12):4332-41. PMC: 2993598. DOI: 10.1172/JCI43918. View

12.

Johnston R, Theman T, Lu F, Terry R, Williams E, Shore S . Diet-induced obesity causes innate airway hyperresponsiveness to methacholine and enhances ozone-induced pulmonary inflammation. J Appl Physiol (1985). 2008; 104(6):1727-35. DOI: 10.1152/japplphysiol.00075.2008. View

13.

Cho Y, Abu-Ali G, Tashiro H, Kasahara D, Brown T, Brand J . The Microbiome Regulates Pulmonary Responses to Ozone in Mice. Am J Respir Cell Mol Biol. 2018; 59(3):346-354. PMC: 6189641. DOI: 10.1165/rcmb.2017-0404OC. View

14.

Trompette A, Gollwitzer E, Yadava K, Sichelstiel A, Sprenger N, Ngom-Bru C . Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat Med. 2014; 20(2):159-66. DOI: 10.1038/nm.3444. View

15.

Williams A, Mathews J, Kasahara D, Wurmbrand A, Chen L, Shore S . Innate and ozone-induced airway hyperresponsiveness in obese mice: role of TNF-α. Am J Physiol Lung Cell Mol Physiol. 2015; 308(11):L1168-77. PMC: 4451401. DOI: 10.1152/ajplung.00393.2014. View

16.

Jiao N, Baker S, Nugent C, Tsompana M, Cai L, Wang Y . Gut microbiome may contribute to insulin resistance and systemic inflammation in obese rodents: a meta-analysis. Physiol Genomics. 2018; 50(4):244-254. DOI: 10.1152/physiolgenomics.00114.2017. View

17.

Beli E, Yan Y, Moldovan L, Vieira C, Gao R, Duan Y . Restructuring of the Gut Microbiome by Intermittent Fasting Prevents Retinopathy and Prolongs Survival in Mice. Diabetes. 2018; 67(9):1867-1879. PMC: 6110320. DOI: 10.2337/db18-0158. View

18.

Bennett W, Hazucha M, Folinsbee L, Bromberg P, Kissling G, London S . Acute pulmonary function response to ozone in young adults as a function of body mass index. Inhal Toxicol. 2007; 19(14):1147-54. PMC: 2253725. DOI: 10.1080/08958370701665475. View

19.

Akinbami L, Fryar C . Current Asthma Prevalence by Weight Status Among Adults: United States, 2001-2014. NCHS Data Brief. 2016; (239):1-8. View

20.

Wang H, Zhang X, Wang S, Li H, Lu Z, Shi J . Mannan-oligosaccharide modulates the obesity and gut microbiota in high-fat diet-fed mice. Food Funct. 2018; 9(7):3916-3929. DOI: 10.1039/c8fo00209f. View