Dietary tryptophan links encephalogenicity of autoreactive T cells with gut microbial ecology

Jana K. Sonner, Melanie Keil, Maren Falk-Paulsen, Neha Mishra, Ateequr Rehman, Magdalena Kramer, Katrin Deumelandt, Julian Röwe, Khwab Sanghvi, Lara Wolf, Anna Landenberg, Hendrik Wolff, Richa Bharti, Iris Oezen, Tobias V. Lanz, Florian Wanke, Yilang Tang, Ines Brandao, Soumya R. Mohapatra, Lisa Epping, Alexandra Grill, Ralph Röth, Beate Niesler, Sven G. Meuth, Christiane A. Opitz, Jürgen G. Okun, Christoph Reinhardt, Florian C. Kurschus, Wolfgang Wick, Helge B. Bode, Philip Rosenstiel and Michael Platten ()
Additional contact information
Jana K. Sonner: German Cancer Research Center (DKFZ)
Melanie Keil: German Cancer Research Center (DKFZ)
Maren Falk-Paulsen: University Kiel
Neha Mishra: University Kiel
Ateequr Rehman: University Kiel
Magdalena Kramer: German Cancer Research Center (DKFZ)
Katrin Deumelandt: German Cancer Research Center (DKFZ)
Julian Röwe: German Cancer Research Center (DKFZ)
Khwab Sanghvi: German Cancer Research Center (DKFZ)
Lara Wolf: German Cancer Research Center (DKFZ)
Anna Landenberg: German Cancer Research Center (DKFZ)
Hendrik Wolff: Goethe-University Frankfurt
Richa Bharti: University Kiel
Iris Oezen: German Cancer Research Center (DKFZ)
Tobias V. Lanz: German Cancer Research Center (DKFZ)
Florian Wanke: Institute for Molecular Medicine
Yilang Tang: Institute for Molecular Medicine
Ines Brandao: University Medical Center of the Johannes Gutenberg University Mainz
Soumya R. Mohapatra: German Cancer Research Center (DKFZ)
Lisa Epping: Department of Neurology with Institute of Translational Neurology
Alexandra Grill: University Medical Center of the Johannes Gutenberg University Mainz
Ralph Röth: University of Heidelberg
Beate Niesler: University of Heidelberg
Sven G. Meuth: Department of Neurology with Institute of Translational Neurology
Christiane A. Opitz: German Cancer Research Center (DKFZ)
Jürgen G. Okun: CCU Children’s Hospital and Metabolic Center Heidelberg
Christoph Reinhardt: University Medical Center of the Johannes Gutenberg University Mainz
Florian C. Kurschus: Institute for Molecular Medicine
Wolfgang Wick: German Cancer Research Center (DKFZ)
Helge B. Bode: Goethe-University Frankfurt
Philip Rosenstiel: University Kiel
Michael Platten: German Cancer Research Center (DKFZ)

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract The interaction between the mammalian host and its resident gut microbiota is known to license adaptive immune responses. Nutritional constituents strongly influence composition and functional properties of the intestinal microbial communities. Here, we report that omission of a single essential amino acid - tryptophan – from the diet abrogates CNS autoimmunity in a mouse model of multiple sclerosis. Dietary tryptophan restriction results in impaired encephalitogenic T cell responses and is accompanied by a mild intestinal inflammatory response and a profound phenotypic shift of gut microbiota. Protective effects of dietary tryptophan restriction are abrogated in germ-free mice, but are independent of canonical host sensors of intracellular tryptophan metabolites. We conclude that dietary tryptophan restriction alters metabolic properties of gut microbiota, which in turn have an impact on encephalitogenic T cell responses. This link between gut microbiota, dietary tryptophan and adaptive immunity may help to develop therapeutic strategies for protection from autoimmune neuroinflammation.

Date: 2019
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DOI: 10.1038/s41467-019-12776-4

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