Butyrate ameliorates allergic airway inflammation by limiting eosinophil trafficking and survival

Anna Theiler; Thomas Bärnthaler; Wolfgang Platzer; Georg Richtig; Miriam Peinhaupt; Sonja Rittchen; Julia Kargl; Trond Ulven; Leigh M Marsh; Gunther Marsche; Rufina Schuligoi; Eva M Sturm; Akos Heinemann

doi:10.1016/j.jaci.2019.05.002

Butyrate ameliorates allergic airway inflammation by limiting eosinophil trafficking and survival

Anna Theiler, Thomas Bärnthaler, Wolfgang Platzer, Georg Richtig, Miriam Peinhaupt, Sonja Rittchen, Julia Kargl, Trond Ulven, Leigh M Marsh, Gunther Marsche, Rufina Schuligoi, Eva M Sturm, Akos Heinemann

32 Citations (Scopus)

Abstract

Background: Lung eosinophilia is a hallmark of asthma, and eosinophils are believed to play a crucial role in the pathogenesis of allergic inflammatory diseases. Short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, are produced in high amounts in the gastrointestinal tract by commensal bacteria and can be absorbed into the bloodstream. Although there is recent evidence that SCFAs are beneficial in allergic asthma models, the effect on eosinophils has remained elusive. Objective: The role of SCFAs was investigated in human eosinophil function and a mouse model of allergic asthma. Methods: Eosinophils were purified from self-reported allergic or healthy donors. Migration, adhesion to the endothelium, and eosinophil survival were studied in vitro. Ca²⁺ flux, apoptosis, mitochondrial membrane potential, and expression of surface markers were determined by using flow cytometry and in part by using real-time PCR. Allergic airway inflammation was assessed in vivo in an ovalbumin-induced asthma model by using invasive spirometry. Results: For the first time, we observed that SCFAs were able to attenuate human eosinophils at several functional levels, including (1) adhesion to the endothelium, (2) migration, and (3) survival. These effects were independent from GPR41 and GPR43 but were accompanied by histone acetylation and mimicked by trichostatin A, a pan–histone deacetylase inhibitor. In vivo butyrate ameliorated allergen-induced airway and lung eosinophilia, reduced type 2 cytokine levels in bronchial fluid, and improved airway hyperresponsiveness in mice. Conclusion: These in vitro and in vivo findings highlight the importance of SCFAs, especially butyrate as a promising therapeutic agent in allergic inflammatory diseases.

Original language	English
Journal	The Journal of allergy and clinical immunology
ISSN	0091-6749
DOIs	https://doi.org/10.1016/j.jaci.2019.05.002
Publication status	Published - Sept 2019

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Theiler, A., Bärnthaler, T., Platzer, W., Richtig, G., Peinhaupt, M., Rittchen, S., Kargl, J., Ulven, T., Marsh, L. M., Marsche, G., Schuligoi, R., Sturm, E. M., & Heinemann, A. (2019). Butyrate ameliorates allergic airway inflammation by limiting eosinophil trafficking and survival. The Journal of allergy and clinical immunology. https://doi.org/10.1016/j.jaci.2019.05.002

@article{813de5a252ae478facc6b30c47695578,

title = "Butyrate ameliorates allergic airway inflammation by limiting eosinophil trafficking and survival",

abstract = "Background: Lung eosinophilia is a hallmark of asthma, and eosinophils are believed to play a crucial role in the pathogenesis of allergic inflammatory diseases. Short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, are produced in high amounts in the gastrointestinal tract by commensal bacteria and can be absorbed into the bloodstream. Although there is recent evidence that SCFAs are beneficial in allergic asthma models, the effect on eosinophils has remained elusive. Objective: The role of SCFAs was investigated in human eosinophil function and a mouse model of allergic asthma. Methods: Eosinophils were purified from self-reported allergic or healthy donors. Migration, adhesion to the endothelium, and eosinophil survival were studied in vitro. Ca2+ flux, apoptosis, mitochondrial membrane potential, and expression of surface markers were determined by using flow cytometry and in part by using real-time PCR. Allergic airway inflammation was assessed in vivo in an ovalbumin-induced asthma model by using invasive spirometry. Results: For the first time, we observed that SCFAs were able to attenuate human eosinophils at several functional levels, including (1) adhesion to the endothelium, (2) migration, and (3) survival. These effects were independent from GPR41 and GPR43 but were accompanied by histone acetylation and mimicked by trichostatin A, a pan–histone deacetylase inhibitor. In vivo butyrate ameliorated allergen-induced airway and lung eosinophilia, reduced type 2 cytokine levels in bronchial fluid, and improved airway hyperresponsiveness in mice. Conclusion: These in vitro and in vivo findings highlight the importance of SCFAs, especially butyrate as a promising therapeutic agent in allergic inflammatory diseases.",

author = "Anna Theiler and Thomas B{\"a}rnthaler and Wolfgang Platzer and Georg Richtig and Miriam Peinhaupt and Sonja Rittchen and Julia Kargl and Trond Ulven and Marsh, {Leigh M} and Gunther Marsche and Rufina Schuligoi and Sturm, {Eva M} and Akos Heinemann",

note = "Copyright {\textcopyright} 2019. Published by Elsevier Inc.",

year = "2019",

month = sep,

doi = "10.1016/j.jaci.2019.05.002",

language = "English",

journal = "The Journal of allergy and clinical immunology",

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T1 - Butyrate ameliorates allergic airway inflammation by limiting eosinophil trafficking and survival

AU - Theiler, Anna

AU - Bärnthaler, Thomas

AU - Platzer, Wolfgang

AU - Richtig, Georg

AU - Peinhaupt, Miriam

AU - Rittchen, Sonja

AU - Kargl, Julia

AU - Ulven, Trond

AU - Marsh, Leigh M

AU - Marsche, Gunther

AU - Schuligoi, Rufina

AU - Sturm, Eva M

AU - Heinemann, Akos

PY - 2019/9

Y1 - 2019/9

N2 - Background: Lung eosinophilia is a hallmark of asthma, and eosinophils are believed to play a crucial role in the pathogenesis of allergic inflammatory diseases. Short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, are produced in high amounts in the gastrointestinal tract by commensal bacteria and can be absorbed into the bloodstream. Although there is recent evidence that SCFAs are beneficial in allergic asthma models, the effect on eosinophils has remained elusive. Objective: The role of SCFAs was investigated in human eosinophil function and a mouse model of allergic asthma. Methods: Eosinophils were purified from self-reported allergic or healthy donors. Migration, adhesion to the endothelium, and eosinophil survival were studied in vitro. Ca2+ flux, apoptosis, mitochondrial membrane potential, and expression of surface markers were determined by using flow cytometry and in part by using real-time PCR. Allergic airway inflammation was assessed in vivo in an ovalbumin-induced asthma model by using invasive spirometry. Results: For the first time, we observed that SCFAs were able to attenuate human eosinophils at several functional levels, including (1) adhesion to the endothelium, (2) migration, and (3) survival. These effects were independent from GPR41 and GPR43 but were accompanied by histone acetylation and mimicked by trichostatin A, a pan–histone deacetylase inhibitor. In vivo butyrate ameliorated allergen-induced airway and lung eosinophilia, reduced type 2 cytokine levels in bronchial fluid, and improved airway hyperresponsiveness in mice. Conclusion: These in vitro and in vivo findings highlight the importance of SCFAs, especially butyrate as a promising therapeutic agent in allergic inflammatory diseases.

AB - Background: Lung eosinophilia is a hallmark of asthma, and eosinophils are believed to play a crucial role in the pathogenesis of allergic inflammatory diseases. Short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, are produced in high amounts in the gastrointestinal tract by commensal bacteria and can be absorbed into the bloodstream. Although there is recent evidence that SCFAs are beneficial in allergic asthma models, the effect on eosinophils has remained elusive. Objective: The role of SCFAs was investigated in human eosinophil function and a mouse model of allergic asthma. Methods: Eosinophils were purified from self-reported allergic or healthy donors. Migration, adhesion to the endothelium, and eosinophil survival were studied in vitro. Ca2+ flux, apoptosis, mitochondrial membrane potential, and expression of surface markers were determined by using flow cytometry and in part by using real-time PCR. Allergic airway inflammation was assessed in vivo in an ovalbumin-induced asthma model by using invasive spirometry. Results: For the first time, we observed that SCFAs were able to attenuate human eosinophils at several functional levels, including (1) adhesion to the endothelium, (2) migration, and (3) survival. These effects were independent from GPR41 and GPR43 but were accompanied by histone acetylation and mimicked by trichostatin A, a pan–histone deacetylase inhibitor. In vivo butyrate ameliorated allergen-induced airway and lung eosinophilia, reduced type 2 cytokine levels in bronchial fluid, and improved airway hyperresponsiveness in mice. Conclusion: These in vitro and in vivo findings highlight the importance of SCFAs, especially butyrate as a promising therapeutic agent in allergic inflammatory diseases.

U2 - 10.1016/j.jaci.2019.05.002

DO - 10.1016/j.jaci.2019.05.002

M3 - Journal article

C2 - 31082458

SN - 0091-6749

JO - The Journal of allergy and clinical immunology

JF - The Journal of allergy and clinical immunology

ER -

Butyrate ameliorates allergic airway inflammation by limiting eosinophil trafficking and survival

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