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

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.

• Authors: Jana K Sonner, Melanie Keil, Maren Falk-Paulsen, Neha Mishra, Ateequr Rehman, Magdalena Kramer, Katrin Deumelandt, Julian Röwe, Khwab Sanghvi, Lara Wolf, Anna von 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, Michael Platten
• Journal: Nature communications (Nat Commun) Vol. 10 Issue 1 Pg. 4877 (10 25 2019) ISSN: 2041-1723 [Electronic] England
• PMID: 31653831 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dietary Proteins
• RNA, Ribosomal, 16S
• Tryptophan

Topics

• Animals
• Autoimmunity (immunology)
• Diet
• Dietary Proteins
• Disease Models, Animal
• Encephalomyelitis, Autoimmune, Experimental (immunology, microbiology)
• Gastrointestinal Microbiome (genetics, immunology)
• Mice
• Multiple Sclerosis
• RNA, Ribosomal, 16S (genetics)
• T-Lymphocytes (immunology)
• Tryptophan