D-tryptophan from probiotic bacteria influences the gut microbiome and allergic airway disease.
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 C11H12N2O2as 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.
Comprehensive Pneumology Center, Ludwig Maximilians University Hospital, Member of the German Center for Lung Research (DZL), and Helmholtz Zentrum München, Munich, Germany.
Inge
I
Kepert
Research Unit Analytical BioGeoChemistry (BGC), Helmholtz Zentrum München, Oberschleissheim, Germany.
Juliano
J
Fonseca
Research Unit Analytical BioGeoChemistry (BGC), Helmholtz Zentrum München, Oberschleissheim, Germany.
Constanze
C
Müller
Comprehensive Pneumology Center, Ludwig Maximilians University Hospital, Member of the German Center for Lung Research (DZL), and Helmholtz Zentrum München, Munich, Germany.
Katrin
K
Milger
Research Unit Microbe-Plant Interactions, Helmholtz Zentrum München, Oberschleissheim, Germany.
Kerstin
K
Hochwind
Research Unit Environmental Genomics, Helmholtz Zentrum München, Oberschleissheim, Germany.
Matea
M
Kostric
Center of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Zentrum München, Member of the German Center for Lung research (DZL), Oberschleissheim, Germany.
Maria
M
Fedoseeva
Center of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Zentrum München, Member of the German Center for Lung research (DZL), Oberschleissheim, Germany.
Caspar
C
Ohnmacht
Comprehensive Pneumology Center, Ludwig Maximilians University Hospital, Member of the German Center for Lung Research (DZL), and Helmholtz Zentrum München, Munich, Germany.
Stefan
S
Dehmel
Comprehensive Pneumology Center, Ludwig Maximilians University Hospital, Member of the German Center for Lung Research (DZL), and Helmholtz Zentrum München, Munich, Germany.
Petra
P
Nathan
Comprehensive Pneumology Center, Ludwig Maximilians University Hospital, Member of the German Center for Lung Research (DZL), and Helmholtz Zentrum München, Munich, Germany; Division of Experimental Asthma Research, Research Center Borstel, Leibniz Center for Medicine and Biosciences, Member of the German Center for Lung Research (DZL), Borstel, Germany.
Sabine
S
Bartel
Comprehensive Pneumology Center, Ludwig Maximilians University Hospital, Member of the German Center for Lung Research (DZL), and Helmholtz Zentrum München, Munich, Germany.
Oliver
O
Eickelberg
Research Unit Environmental Genomics, Helmholtz Zentrum München, Oberschleissheim, Germany.
Michael
M
Schloter
Research Unit Microbe-Plant Interactions, Helmholtz Zentrum München, Oberschleissheim, Germany.
Anton
A
Hartmann
Research Unit Analytical BioGeoChemistry (BGC), Helmholtz Zentrum München, Oberschleissheim, Germany; Analytical Food Chemistry, Technische Universität Muenchen, Freising, Germany.
Philippe
P
Schmitt-Kopplin
Comprehensive Pneumology Center, Ludwig Maximilians University Hospital, Member of the German Center for Lung Research (DZL), and Helmholtz Zentrum München, Munich, Germany; Division of Experimental Asthma Research, Research Center Borstel, Leibniz Center for Medicine and Biosciences, Member of the German Center for Lung Research (DZL), Borstel, Germany; Institute for Experimental Medicine, Christian-Albrechts-Universitaet zu Kiel, Kiel, Germany. Electronic address: skrauss-etschmann@fz-borstel.de.
Susanne
S
Krauss-Etschmann
D000818:Animals; D001249:Asthma / Q000276:immunology*; D001419:Bacteria / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D003713:Dendritic Cells; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D006801:Humans; D008070:Lipopolysaccharides; D008807:Mice, Inbred BALB C; D019936:Probiotics; D014364:Tryptophan / Q000096:biosynthesis*
D016207:Cytokines; D008070:Lipopolysaccharides; D014364:Tryptophan
D-tryptophan; allergic airway disease; bacterial substance; gut microbiota; immune modulation; probiotic bacteria; screening