Gut microorganisms act together to exacerbate inflammation in spinal cords

• Published in: Nature (London) Vol. 585; no. 7823; pp. 102 - 106
• Main Authors: Miyauchi, Eiji, Kim, Seok-Won, Suda, Wataru, Kawasumi, Masami, Onawa, Satoshi, Taguchi-Atarashi, Naoko, Morita, Hidetoshi, Taylor, Todd D., Hattori, Masahira, Ohno, Hiroshi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.09.2020; Nature Publishing Group
• Subjects: 13/31; 38; 38/23; 631/250/38; 631/326/41/547; 64/60; Animal models; Animals; Antibiotics; Autoimmune diseases; Bacteria; CD4 antigen; Cytokines; Dendritic cells; Digestive system; Disease Models, Animal; Encephalomyelitis; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - microbiology; Encephalomyelitis, Autoimmune, Experimental - pathology; Encephalomyelitis, Autoimmune, Experimental - prevention & control; Experimental allergic encephalomyelitis; Female; Gastrointestinal Microbiome - immunology; Gastrointestinal tract; Gene expression; Genomes; Germ-Free Life; Germfree; Glycoproteins; Humanities and Social Sciences; Inflammation - immunology; Inflammation - pathology; Intestinal microflora; Intestine; Intestine, Small - immunology; Intestine, Small - microbiology; Intestine, Small - pathology; Lactobacillus reuteri - chemistry; Lactobacillus reuteri - immunology; Lactobacillus reuteri - pathogenicity; Lymphocytes; Lymphocytes T; Male; Mice; Microbiota; Microorganisms; multidisciplinary; Multiple sclerosis; Multiple Sclerosis - immunology; Multiple Sclerosis - microbiology; Multiple Sclerosis - pathology; Myelin; Myelin-Oligodendrocyte Glycoprotein - chemistry; Myelin-Oligodendrocyte Glycoprotein - immunology; Oligodendrocyte-myelin glycoprotein; Pathogenicity; Pathogens; Peptides; Rodents; Science; Science (multidisciplinary); Signs and symptoms; Small intestine; Spinal cord; Spinal Cord - immunology; Spinal Cord - pathology; Synergistic effect; T-Lymphocytes - immunology; T-Lymphocytes - pathology; Th17 Cells - immunology; Th17 Cells - pathology
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-020-2634-9

Accumulating evidence indicates that gut microorganisms have a pathogenic role in autoimmune diseases, including in multiple sclerosis 1 . Studies of experimental autoimmune encephalomyelitis (an animal model of multiple sclerosis) 2 , 3 , as well as human studies 4 – 6 , have implicated gut microorganisms in the development or severity of multiple sclerosis. However, it remains unclear how gut microorganisms act on the inflammation of extra-intestinal tissues such as the spinal cord. Here we show that two distinct signals from gut microorganisms coordinately activate autoreactive T cells in the small intestine that respond specifically to myelin oligodendrocyte glycoprotein (MOG). After induction of experimental autoimmune encephalomyelitis in mice, MOG-specific CD4 + T cells are observed in the small intestine. Experiments using germ-free mice that were monocolonized with microorganisms from the small intestine demonstrated that a newly isolated strain in the family Erysipelotrichaceae acts similarly to an adjuvant to enhance the responses of T helper 17 cells. Shotgun sequencing of the contents of the small intestine revealed a strain of Lactobacillus reuteri that possesses peptides that potentially mimic MOG. Mice that were co-colonized with these two strains showed experimental autoimmune encephalomyelitis symptoms that were more severe than those of germ-free or monocolonized mice. These data suggest that the synergistic effects that result from the presence of these microorganisms should be considered in the pathogenicity of multiple sclerosis, and that further study of these microorganisms may lead to preventive strategies for this disease. Germ-free mice co-colonized with two bacterial strains from the small intestinal flora showed increased susceptibility to experimental autoimmune encephalomyelitis, implicating the synergistic effects of these microorganisms in this mouse model of multiple sclerosis.