Butyrate ameliorates allergic airway inflammation by limiting eosinophil trafficking and survival

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

doi:10.1016/j.jaci.2019.05.002

Cited by 148 publications

(138 citation statements)

References 58 publications

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“…Recent studies have reported that SCFAs may reduce allergic airway inflammation by limiting eosinophil trafficking and survival. 6,7 The present study demonstrated that clostridiales was significantly elevated in allergic mice after azithromycin treatment, so we assessed alterations in the fecal levels of SCFAs. The propionate level was significantly decreased in the cefixime group (not in the azithromycin group) compared with the OVA-treated group; the acetate level was higher in the azithromycin group than in the OVA-treated group.…”

Section: Altered Gut Microbiota By Azithromycin Attenuates Airway Infmentioning

confidence: 99%

Altered gut microbiota by azithromycin attenuates airway inflammation in allergic asthma

Park

Choi

Lee

et al. 2020

Journal of Allergy and Clinical Immunology

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Section: Altered Gut Microbiota By Azithromycin Attenuates Airway Infmentioning

confidence: 99%

Altered gut microbiota by azithromycin attenuates airway inflammation in allergic asthma

Park

Choi

Lee

et al. 2020

Journal of Allergy and Clinical Immunology

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“…Notably, HDAC inhibition requires millimolar concentrations of SCFA usually seen in the colon (vs micromolar lung SCFA levels). Additionally, FFAR2-independent effects of SCFAs have been reported in lung eosinophils and mast cells in asthma and allergic airway disease (16,49).…”

Section: Discussionmentioning

confidence: 99%

Lung Immune Tone Regulation by the Gut-Lung Immune Axis: Short-chain Fatty Acid Receptors FFAR2 and FFAR3, and IL-1β Expression Profiling in Mouse and Human Lung

Liu

Tian

Maruyama

et al. 2020

Preprint

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Microbial metabolites produced by the gut microbiome, such as short-chain fatty acids (SCFA), can influence both local intestinal and distant lung physiology and response to injury. However, how lung immune activity is regulated by SCFAs is unknown. We examined fresh human lung tissue and observed the presence of SCFAs with large inter-individual and even intra-lobe variability. In vitro, SCFAs were capable of modifying the metabolic programming in both resting and LPS-exposed alveolar macrophages (AM). Additionally, since we hypothesized that lung immune tone could be defined through priming of the inflammasome (aka signal 1), we interrogated naïve mouse lungs for pro-IL-1β message and localized its presence within the alveolar space in situ, specifically in AM subsets, and in close proximity to alveolar type 2 epithelial (AT2) cells. We established that metabolically active gut microbiota, that produce SCFAs, can transmit LPS and SCFAs to the lung (potential sources of signal 1), and thereby could regulate lung immune tone and metabolic programming. To understand how murine lung cells sensed and upregulated IL-1β in response to gut-microbiome factors, we determined that in vitro, AM and AT2 cells expressed SCFA receptors, FFAR2, FFAR3, and IL-1β but with different expression patterns and LPS-inducibility. Finally, we observed that IL-1β, FFAR2 and FFAR3 were expressed both in isolated human AM and AT2 cells ex-vivo, but in fresh human lung sections in situ, only AM expressed IL-1β at rest and after LPS challenge. Together, this translational study using mouse and human lung tissue and cells supports an important role for the gut microbiome and SCFAs in regulating lung immune tone.

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“…Other models of allergic airways disease have reported reduced eosinophilic-mediated type 2 inflammation in mice injected with butyrate [89]. In human eosinophils, SCFA attenuated migration, adhesion and survival via GPCR independent mechanisms accompanied by increased histone acetylation [89].…”

Section: Scfa Effects On Innate Immune Functionmentioning

confidence: 97%

The Potential Effects of Short-Chain Fatty Acids on the Epigenetic Regulation of Innate Immune Memory

2020

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The regulation of innate immunity is substantially more ‘plastic’ than previously appreciated. Innate immune memory (manifested through trained immunity and tolerance) is a recently described epigenetic phenomenon that is a model example, with broad implications for infectious disease, allergy and autoimmunity. Training the innate immune system to combat infections and temper inappropriate responses in non-communicable diseases will likely be an area of intense research. Innate immunity is influenced by short chain fatty acids, which are the natural products of digestion by the intestinal microbiota that possess inherent histone deacetylase inhibitory properties. It therefore stands to reason that a healthy gut microbiome may well influence mucosal and systemic trained immunity via short chain fatty acids. There is a lack of data on this specific topic, and we discuss potential relationships based on available and preliminary evidence. Understanding the link between intestinal microbiome composition, capacity for short chain fatty acid production and downstream effects on innate immune memory in early life will have important implications for host immunobiology. In this review we explore the intersection between the gut microbiota, short chain fatty acids and epigenetic regulation of innate immunity with a focus on early life.

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Butyrate ameliorates allergic airway inflammation by limiting eosinophil trafficking and survival

Cited by 148 publications

References 58 publications

Altered gut microbiota by azithromycin attenuates airway inflammation in allergic asthma

Altered gut microbiota by azithromycin attenuates airway inflammation in allergic asthma

Lung Immune Tone Regulation by the Gut-Lung Immune Axis: Short-chain Fatty Acid Receptors FFAR2 and FFAR3, and IL-1β Expression Profiling in Mouse and Human Lung

The Potential Effects of Short-Chain Fatty Acids on the Epigenetic Regulation of Innate Immune Memory

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