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Kepert, I. ; Fonseca, J. ; Müller, C. ; Milger, K. ; Hochwind, K. ; Kostric, M. ; Fedoseeva, M. ; Ohnmacht, C. ; Dehmel, S. ; Nathan, P. ; Bartel, S. ; Eickelberg, O. ; Schloter, M. ; Hartmann, A. ; Schmitt-Kopplin, P. ; Krauss-Etschmann, S.

D-Tryptophan from probiotic bacteria influences the gut microbiome and allergic airway disease.

J. Allergy Clin. Immunol. 139, 1525-1535 (2017)

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BACKGROUND: Chronic immune diseases (CIDs), such as asthma, are highly prevalent. Currently available pharmaceuticals improve symptoms, but cannot cure the disease. This prompted demands for alternatives to pharmaceuticals such as probiotics for prevention of allergic disease. However, clinical trials have given inconsistent results. This is at least partly explained by the highly complex crosstalk among probiotic bacteria, the host´s microbiota, and immune cells. The identification of a bioactive substance from probiotic bacteria could circumvent this difficulty. OBJECTIVE: To identify and characterize a bioactive, probiotic metabolite for potential prevention of allergic airway disease. METHODS: Probiotic supernatants were screened for their ability to concordantly lower the constitutive CCL17 secretion of a human Hodgkin lymphoma cell line and prevent upregulation of costimulatory molecules of LPS-stimulated human dendritic cells. RESULTS: Supernatants from 13 of 37 tested probiotic strains showed immunoactivity. Bioassay-guided chromatographic fractionation of two supernatants according to polarity, followed by total ion chromatograms and mass spectrometry, yielded C11H12N2O2 as molecular formula of a bioactive substance. Proton nuclear magnetic resonance and enantiomeric separation identified D-Tryptophan. In contrast, L-Tryptophan and eleven other D-amino acids were inactive. Feeding D-Tryptophan to mice prior to experimental asthma induction, increased numbers of lung and gut regulatory T cells, lowered lung Th2 responses, and ameliorated allergic airway inflammation and hyperresponsiveness. Allergic airway inflammation reduced the gut microbial diversity, which was increased by D-Tryptophan. CONCLUSIONS: D-Tryptophan is a newly identified product from probiotic bacteria. Our findings support the concept that defined bacterial products might be exploited in novel preventative strategies for CIDs.

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