1. Microbial metabolism of L-tyrosine protects against allergic airway inflammation.
- Author
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Wypych TP, Pattaroni C, Perdijk O, Yap C, Trompette A, Anderson D, Creek DJ, Harris NL, and Marsland BJ
- Subjects
- Administration, Oral, Allergens, Animals, Antibodies immunology, Antibody Diversity, Bacteria immunology, Cells, Cultured, Chemokine CCL20 metabolism, Coculture Techniques, Cresols administration & dosage, Disease Models, Animal, ErbB Receptors metabolism, Female, Host-Pathogen Interactions, Injections, Intravenous, Lung immunology, Lung pathology, Male, Mice, Inbred C57BL, Mice, Transgenic, Pneumonia immunology, Pneumonia metabolism, Pneumonia microbiology, Respiratory Hypersensitivity immunology, Respiratory Hypersensitivity metabolism, Respiratory Hypersensitivity microbiology, Signal Transduction, Sulfuric Acid Esters administration & dosage, Toll-Like Receptor 4 metabolism, Tyrosine administration & dosage, Mice, Antibodies metabolism, Bacteria metabolism, Cresols metabolism, Gastrointestinal Microbiome, Intestines microbiology, Lung metabolism, Pneumonia prevention & control, Respiratory Hypersensitivity prevention & control, Sulfuric Acid Esters metabolism, Tyrosine metabolism
- Abstract
The constituents of the gut microbiome are determined by the local habitat, which itself is shaped by immunological pressures, such as mucosal IgA. Using a mouse model of restricted antibody repertoire, we identified a role for antibody-microbe interactions in shaping a community of bacteria with an enhanced capacity to metabolize L-tyrosine. This model led to increased concentrations of p-cresol sulfate (PCS), which protected the host against allergic airway inflammation. PCS selectively reduced CCL20 production by airway epithelial cells due to an uncoupling of epidermal growth factor receptor (EGFR) and Toll-like receptor 4 (TLR4) signaling. Together, these data reveal a gut microbe-derived metabolite pathway that acts distally on the airway epithelium to reduce allergic airway responses, such as those underpinning asthma.
- Published
- 2021
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