Microbiome-Driven Allergic Lung Inflammation Is Ameliorated by Short-Chain Fatty Acids
Open accessAbstract
The mammalian gastrointestinal tract harbors a microbial community with metabolic activity critical for host health, including metabolites that can modulate effector functions of immune cells. Mice treated with vancomycin have an altered microbiome and metabolite profile, exhibit exacerbated T helper type 2 cell (Th2) responses, and are more susceptible to allergic lung inflammation. Here we show that dietary supplementation with short-chain fatty acids (SCFAs) ameliorates this enhanced asthma susceptibility by modulating the activity of T cells and dendritic cells (DCs). Dysbiotic mice treated with SCFAs have fewer interleukin-4 (IL4)-producing CD4+ T cells and decreased levels of circulating immunoglobulin E (IgE). In addition, DCs exposed to SCFAs activate T cells less robustly, are less motile in response to CCL19 in vitro, and exhibit a dampened ability to transport inhaled allergens to lung draining nodes. Our data thus demonstrate that gut dysbiosis can exacerbate allergic lung inflammation through both T cell- and DC-dependent mechanisms that are inhibited by SCFAs.
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SCFA treatment of dysbiotic mice regulated dendritic cell and T cell activity and reduced circulating IgE and IL-4-producing CD4+ T cells, alleviating increased asthma susceptibility.
“SCFA treatment of dysbiotic mice regulated the activity of dendritic cells (DCs) and T cells and reduced the levels of circulating immunoglobulin E (IgE) and IL-4-producing CD4 + T cells, thus alleviating increased asthma susceptibility.”
From The Role of Gut Microbiota in Lung Cancer: From Carcinogenesis to Immunotherapy (2021) · cites this paper as [42]
Dendritic cells exposed to SCFAs weakly activate T cells with lower responsiveness to CCL19 and inhibited capacity to deliver inhaled allergens to pulmonary draining lymph nodes.
“dendritic cells exposed to SCFAs less weakly activate T cells with lower responsiveness to CCL19 and present inhibited capacity to deliver inhaled allergens to pulmonary draining lymph nodes (42).”
From The Role of Gut Microbiota in Lung Cancer: From Carcinogenesis to Immunotherapy (2021) · cites this paper as [42]
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- Authors
- Cait, A., Hughes, M. R., Antignano, F., Cait, J., Dimitriu, P. A., Maas, K. R., Reynolds, L. A., Hacker, L., Mohr, J., Finlay, B. B., Zaph, C., McNagny, K. M., & Mohn, W. W.
- Affiliations
- University of British Columbia (CA)
- Corresponding author
- Hughes, M R
- Mohn, W W
- ORCID
- Venue
- Mucosal Immunology
- Publisher
- Elsevier BV
- Published
- 2018-05
- Volume
- 11
- Issue
- 3
- Pages
- 785-795
- ISSN
- 1933-0219 (ISSN-L)
- OpenAlex
- W2765759949
- Cited by
- 394
- References
- 49
- Citations by year
- 2026: 42 · 2025: 56 · 2024: 66 · 2023: 55 · 2022: 64 · 2021: 41 · 2020: 42 · 2019: 18 · 2018: 8 · 2013: 1
- FWCI
- 7.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Mucosal Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Keywords
- short-chain fatty acids, allergic lung inflammation, asthma, gut microbiota, gut dysbiosis, vancomycin, Th2 cells, IL-4, immunoglobulin E, dendritic cells, T cell activation, CCL19, dietary supplementation
- MeSH terms
- Gastrointestinal Microbiome, Allergens, Animals, Asthma, Dendritic Cells, Fatty Acids, Volatile, Hypersensitivity, Lymphocyte Activation, Mice, Inbred C57BL, Pneumonia, Vancomycin, Interleukin-4, Antigen Presentation, Mice, Knockout, Th2 Cells, Dietary Supplements, Mice, Chemokine CCL19, Microbiota, Dysbiosis
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