Journal Article

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

Mishra, Neha, Kramer, Magdalena, Tang, Yilang, Röth, Ralph, Deumelandt, Katrin, Röwe, Julian, Niesler, Beate, Sonner, Jana K., Rehman, Ateequr, Brandao, Ines, Meuth, Sven G., Grill, Alexandra, Sanghvi, Khwab, Wick, Wolfgang, Falk-Paulsen, Maren, Rosenstiel, Philip, Bode, Helge B., Epping, Lisa, Opitz, Christiane A., Kurschus, Florian C., Platten, Michael, Bharti, Richa, von Landenberg, Anna, Keil, Melanie, Wolf, Lara, Reinhardt, Christoph, Okun, Jürgen G., Wolff, Hendrik, Oezen, Iris, Mohapatra, Soumya R., Lanz, Tobias V., Wanke, Florian

2019

Overview

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. Food intake shapes intestinal microbiome composition, which in turn shapes adaptive immune responses. Here the authors show that dietary tryptophan restriction (DTR) protects mice from subsequent autoimmune neuropathology challenge by altering intestinal microbiota, highlighting the potential of diet-regulated microbiota to prevent immune pathology.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 49 / 49/23 / 49/31 / 49/61 / 631/250/371 / 631/250/38 / 631/326/2565/2134 / 692/699/375/1666 / 692/700/2814 / Adaptive immunity / Amino acids / Animals / Autoimmunity / Autoimmunity - immunology / Diet / Dietary Proteins / Digestive system / Disease Models, Animal / Encephalomyelitis, Autoimmune, Experimental - immunology / Encephalomyelitis, Autoimmune, Experimental - microbiology / Gastrointestinal Microbiome - genetics / Gastrointestinal Microbiome - immunology / Gastrointestinal tract / Germfree / Humanities and Social Sciences / Inflammation / Inflammatory response / Intestinal microflora / Intestine / Lymphocytes / Lymphocytes T / Metabolites / Mice / Microbial activity / Microbiota / Microorganisms / multidisciplinary / Multiple Sclerosis / RNA, Ribosomal, 16S - genetics / Science / Science (multidisciplinary) / T-Lymphocytes - immunology / Tryptophan