The Microbiome Regulates Pulmonary Responses to Ozone in Mice

Cho, Youngji; Abu-Ali, Galeb; Tashiro, Hiroki; Kasahara, David I.; Brown, Traci A.; Brand, Jeffrey D.; Mathews, Joel; Huttenhower, Curtis; Shore, Stephanie A.

doi:10.1165/rcmb.2017-0404oc

Cited by 52 publications

(88 citation statements)

References 54 publications

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“…Our data (127) indicate that the microbiome also plays a role in the asthma-like phenotype of mice to the non allergic asthma trigger, ozone. However, this role is different from the role of the microbiome in allergic airways disease models.…”

Section: Mechanistic Basis For the Role Of Obesity In Severe Asthmamentioning

confidence: 71%

“…SCFAs enter the blood stream and alter both intestinal and bone marrow immune cells ultimately altering the dendritic cells that are required for allergen-mediated immune responses in the lungs. SCFAs also appear to contribute to the role of the microbiome in ozone-induced AHR in mice, though the role of SCFAs differs in this non allergic model (127). …”

Section: Mechanistic Basis For the Role Of Obesity In Severe Asthmamentioning

confidence: 99%

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Obesity and severe asthma

Tashiro

Shore

2019

Allergology International

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105

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Obesity is an important global health issue for both children and adults. Obesity increases the prevalence and incidence of asthma and also increases the risk for severe asthma. Here we describe the features of severe asthma phenotypes for which obesity is a defining characteristic, including steroid resistance, airway inflammation, and co-morbidities. We also review current concepts regarding the mechanistic basis for the impact of obesity in severe asthma, including possible roles for vitamin D deficiency, systemic inflammation, and the microbiome. Finally, we describe data indicating a role for diet, weight loss, and exercise in the treatment of severe asthma with obesity. Better understanding of the mechanistic basis for the role of obesity in severe asthma could lead to new therapeutic options for this population.

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Section: Mechanistic Basis For the Role Of Obesity In Severe Asthmamentioning

confidence: 71%

Section: Mechanistic Basis For the Role Of Obesity In Severe Asthmamentioning

confidence: 99%

Obesity and severe asthma

Tashiro

Shore

2019

Allergology International

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105

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“…Results are the mean + SE of 4-7 mice/group. # p < 0.05 versus chow fed mice with same genotype and housing; % p < 0.05 versus WT mice with same diet and housing; $ p < 0.05 versus same housed mice with the same diet and genotype the lung microbiome because previous data from our lab suggest that it is the gut and not the lung microbiome that accounts for the role of the microbiome in pulmonary responses to ozone [33]. In chow-fed same housed mice, the Simpson index, a measure of ecological diversity, was significantly lower in ST2-deficient than WT same housed (Fig.…”

Section: Effect Of St2 Deficiency and Cohousing On The Gut Microbial mentioning

confidence: 95%

IL-33, diet-induced obesity, and pulmonary responses to ozone

Kasahara¹,

Shore²

2020

Respir Res

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Background: Obesity augments pulmonary responses to ozone. We have reported that IL-33 contributes to these effects of obesity in db/db mice. The purpose of this study was to determine whether IL-33 also contributes to obesity-related changes in the response to ozone in mice with diet-induced obesity. Methods: Male wildtype C57BL/6 mice and mice deficient in ST2, the IL-33 receptor, were placed on chow or high fat diets for 12 weeks from weaning. Because the microbiome has been implicated in obesity-related changes in the pulmonary response to ozone, mice were either housed with other mice of the same genotype (same housed) or with mice of the opposite genotype (cohoused). Cohousing transfers the gut microbiome from one mouse to its cagemates. Results: Diet-induced increases in body mass were not affected by ST2 deficiency or cohousing. In same housed mice, ST2 deficiency reduced ozone-induced airway hyperresponsiveness and neutrophil recruitment in chow-fed but not HFDfed mice even though ST2 deficiency reduced bronchoalveolar lavage IL-5 in both diet groups. In chow-fed mice, cohousing abolished ST2-related reductions in ozone-induced airway hyperresponsiveness and neutrophil recruitment, but in HFD-fed mice, no effect of cohousing on these responses to ozone was observed. In chow-fed mice, ST2 deficiency and cohousing caused changes in the gut microbiome. High fat diet-feeding caused marked changes in the gut microbiome and overrode both ST2-related and cohousing-related differences in the gut microbiome observed in chow-fed mice. Conclusion: Our data indicate a role for IL-33 in pulmonary responses to ozone in chow-fed but not high fat diet-fed mice and are consistent with the hypothesis that these diet-related differences in the role of IL-33 are the result of changes in the gut microbiome.

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“…Androgen‐induced changes in the microbiome could also be involved in O 3 ‐induced AHR. We have reported that antibiotics and germ‐free conditions both attenuate O 3 ‐induced AHR in male mice (Cho et al, ) and that sex differences in O 3 ‐induced AHR are abolished after antibiotic treatment (Cho et al, ). There are sex differences in the gut microbiome (Cho et al, ) , (Markle et al, ) that only appear after puberty (Markle et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…We have reported that antibiotics and germ‐free conditions both attenuate O 3 ‐induced AHR in male mice (Cho et al, ) and that sex differences in O 3 ‐induced AHR are abolished after antibiotic treatment (Cho et al, ). There are sex differences in the gut microbiome (Cho et al, ) , (Markle et al, ) that only appear after puberty (Markle et al, ). Furthermore, castration has been shown to alter the gut microbiome (Markle et al, ; Org et al, ).…”

Section: Discussionmentioning

confidence: 99%

Androgens augment pulmonary responses to ozone in mice

et al. 2019

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Ozone causes airway hyperresponsiveness, a defining feature of asthma, and is an asthma trigger. In mice, ozone‐induced airway hyperresponsiveness is greater in males than in females, suggesting a role for sex hormones in the response to ozone. To examine the role of androgens in these sex differences, we castrated 4‐week‐old mice. Controls underwent sham surgery. At 8 weeks of age, mice were exposed to ozone (2ppm, 3 h) or room air. Twenty‐four hours later, mice were anesthetized and measurements of airway responsiveness to inhaled aerosolized methacholine were made. Mice were then euthanized and bronchoalveolar lavage was performed. Castration attenuated ozone‐induced airway hyperresponsiveness and reduced bronchoalveolar lavage cells. In intact males, flutamide, an androgen receptor inhibitor, had similar effects to castration. Bronchoalveolar lavage concentrations of several cytokines were reduced by either castration or flutamide treatment, but only IL‐1α was reduced by both castration and flutamide. Furthermore, an anti‐IL‐1α antibody reduced bronchoalveolar lavage neutrophils in intact males, although it did not alter ozone‐induced airway hyperresponsiveness. Our data indicate that androgens augment pulmonary responses to ozone and that IL‐1α may contribute to the effects of androgens on ozone‐induced cellular inflammation but not airway hyperresponsiveness.

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The Microbiome Regulates Pulmonary Responses to Ozone in Mice

Cited by 52 publications

References 54 publications

Obesity and severe asthma

Obesity and severe asthma

IL-33, diet-induced obesity, and pulmonary responses to ozone

Androgens augment pulmonary responses to ozone in mice

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