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

Inge Kepert, Juliano Fonseca, Constanze Müller, Katrin Milger, Kerstin Hochwind, Matea Kostric, Maria Fedoseeva, Caspar Ohnmacht, Stefan Dehmel, Petra Nathan, Sabine Bartel, Oliver Eickelberg, Michael Schloter, Anton Hartmann, Philippe Schmitt-Kopplin, Susanne Krauss-Etschmann*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

54 Citations (Scopus)

Abstract

Background Chronic immune diseases, 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 the prevention of allergic disease. However, clinical trials have produced 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 We sought 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 decrease 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 2 supernatants according to polarity, followed by total ion chromatography and mass spectrometry, yielded C11H12N2O2 as the molecular formula of a bioactive substance. Proton nuclear magnetic resonance and enantiomeric separation identified D-tryptophan. In contrast, L-tryptophan and 11 other D-amino acids were inactive. Feeding D-tryptophan to mice before experimental asthma induction increased numbers of lung and gut regulatory T cells, decreased lung TH2 responses, and ameliorated allergic airway inflammation and hyperresponsiveness. Allergic airway inflammation reduced 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 can be exploited in novel preventative strategies for chronic immune diseases.

Original languageEnglish
Pages (from-to)1525-1535
Number of pages11
JournalJournal of Allergy and Clinical Immunology
Volume139
Issue number5
DOIs
Publication statusPublished - May-2017
Externally publishedYes

Keywords

  • allergic airway disease
  • bacterial substance
  • D-tryptophan
  • gut microbiota
  • immune modulation
  • probiotic bacteria
  • screening

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