Department of Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Medicine, Division of Rheumatology, New York University School of Medicine, New York, United States.
Sci Rep. 2017 Nov 15;7(1):15613. 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.
在新发和慢性自身免疫性炎症性关节炎患者中观察到肠道微生物组的紊乱。然而,目前尚不清楚这些改变是在关节炎发生之前发生的,还是疾病的结果。口服抗生素或无菌条件下的肠道微生物群调节可以预防小鼠关节炎。然而,关节炎发病后调节微生物群的治疗潜力尚未得到很好的描述。我们在这里表明,在胶原诱导性关节炎(CIA)的临床前阶段,肠道微生物群落发生了明显变化。厚壁菌门的丰度降低,特别是 S24-7 科和拟杆菌科,而梭菌科和变形菌门,如瘤胃球菌科、毛螺旋菌科和脱硫弧菌科,则在关节炎的免疫启动阶段扩张。此外,我们发现固有层 Th17 细胞的丰度,而不是 Th1 细胞,与关节炎的严重程度高度相关。在已建立的关节炎期间消除肠道微生物群特异性地减少了肠道 Th17 细胞并减轻了关节炎。这些作用与回肠和滑膜组织中血清淀粉样蛋白 A 表达的减少有关。我们的观察表明,肠道微生物组的紊乱先于关节炎发生,而关节炎发病后调节肠道微生物群可能提供治疗机会。