Alteration of the intestinal microbiome characterizes preclinical inflammatory arthritis in mice and its modulation attenuates established arthritis

• Published in: Scientific reports Vol. 7; no. 1; pp. 15613 - 12
• Main Authors: Rogier, Rebecca, Evans-Marin, Heather, Manasson, Julia, van der Kraan, Peter M., Walgreen, Birgitte, Helsen, Monique M., van den Bersselaar, Liduine A., van de Loo, Fons A., van Lent, Peter L., Abramson, Steven B., van den Berg, Wim B., Koenders, Marije I., Scher, Jose U., Abdollahi-Roodsaz, Shahla
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.11.2017; Nature Publishing Group
• Subjects: 13/106; 13/21; 13/31; 38/23; 45/77; 45/90; 631/250/2152/1566/1618; 631/250/38; Amyloid; Animals; Antibiotics; Arthritis; Arthritis, Experimental - genetics; Arthritis, Experimental - immunology; Arthritis, Experimental - microbiology; Bacteroidetes - genetics; Collagen; Disease Models, Animal; Firmicutes - genetics; Gastrointestinal Microbiome - genetics; Germfree; Helper cells; Humanities and Social Sciences; Humans; Ileum; Inflammation; Inflammation - genetics; Inflammation - immunology; Inflammation - microbiology; Inflammation - pathology; Intestinal microflora; Intestine; Lamina propria; Lymphocytes T; Mice; Microorganisms; multidisciplinary; Proteobacteria - genetics; RNA, Ribosomal, 16S - genetics; Science; Science (multidisciplinary); Serum Amyloid A Protein - metabolism; Th1 Cells - immunology; Th17 Cells - immunology; Th17 Cells - microbiology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-15802-x

Perturbations of the intestinal microbiome have been observed in patients with new-onset and chronic autoimmune inflammatory arthritis. However, it is currently unknown whether these alterations precede the development of arthritis or are rather a consequence of disease. Modulation of intestinal microbiota by oral antibiotics or germ-free condition can prevent arthritis in mice. Yet, the therapeutic potential of modulation of the microbiota after the onset of arthritis is not well characterized. We here show that the intestinal microbial community undergoes marked changes in the preclinical phase of collagen induced arthritis (CIA). The abundance of the phylum Bacteroidetes, specifically families S24-7 and Bacteroidaceae was reduced, whereas Firmicutes and Proteobacteria, such as Ruminococcaceae, Lachnospiraceae and Desulfovibrinocaceae, were expanded during the immune-priming phase of arthritis. In addition, we found that the abundance of lamina propria Th17, but not Th1, cells is highly correlated with the severity of arthritis. Elimination of the intestinal microbiota during established arthritis specifically reduced intestinal Th17 cells and attenuated arthritis. These effects were associated with reduced serum amyloid A expression in ileum and synovial tissue. Our observations suggest that intestinal microbiota perturbations precede arthritis, and that modulation of the intestinal microbiota after the onset of arthritis may offer therapeutic opportunities.