Skip to main content
Top

20-09-2016 | Microbiome | Article

The human microbiome and juvenile idiopathic arthritis

Journal: Pediatric Rheumatology

Authors: Anouk Verwoerd, Nienke M. Ter Haar, Sytze de Roock, Sebastiaan J. Vastert, Debby Bogaert

Publisher: BioMed Central

Abstract

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood. The pathogenesis of JIA is thought to be the result of a combination of host genetic and environmental triggers. However, the precise factors that determine one’s susceptibility to JIA remain to be unravelled. The microbiome has received increasing attention as a potential contributing factor to the development of a wide array of immune-mediated diseases, including inflammatory bowel disease, type 1 diabetes and rheumatoid arthritis. Also in JIA, there is accumulating evidence that the composition of the microbiome is different from healthy individuals. A growing body of evidence indeed suggests that, among others, the microbiome may influence the development of the immune system, the integrity of the intestinal mucosal barrier, and the differentiation of T cell subsets. In turn, this might lead to dysregulation of the immune system, thereby possibly playing a role in the development of JIA. The potential to manipulate the microbiome, for example by faecal microbial transplantation, might then offer perspectives for future therapeutic interventions. Before we can think of such interventions, we need to first obtain a deeper understanding of the cause and effect relationship between JIA and the microbiome. In this review, we discuss the existing evidence for the involvement of the microbiome in JIA pathogenesis and explore the potential mechanisms through which the microbiome may influence the development of autoimmunity in general and JIA specifically.
Literature
1.
Prakken B, Albani S, Martini A. Juvenile idiopathic arthritis. Lancet. 2011;377:2138–49.CrossRefPubMed
2.
Macaubas C, Nguyen K, Milojevic D, Park JL, Mellins ED. Oligoarticular and polyarticular JIA: epidemiology and pathogenesis. Nat Rev Rheumatol. 2009;5:616–26.CrossRefPubMedPubMedCentral
3.
Kamada N, Seo SU, Chen GY, Nunez G. Role of the gut microbiota in immunity and inflammatory disease. Nat Rev Immunol. 2013;13:321–35.CrossRefPubMed
4.
Cho I, Blaser MJ. The human microbiome: at the interface of health and disease. Nat Rev Genet. 2012;13:260–70.PubMedPubMedCentral
5.
Missaghi B, Barkema HW, Madsen KL, Ghosh S. Perturbation of the human microbiome as a contributor to inflammatory bowel disease. Pathogens. 2014;3:510–27.CrossRefPubMedPubMedCentral
6.
Giongo A, Gano KA, Crabb DB, Mukherjee N, Novelo LL, Casella G, et al. Toward defining the autoimmune microbiome for type 1 diabetes. ISME J. 2011;5:82–91.CrossRefPubMed
7.
Scher JU, Abramson SB. The microbiome and rheumatoid arthritis. Nat Rev Rheumatol. 2011;7:569–78.PubMedPubMedCentral
8.
Ruff WE, Kriegel MA. Autoimmune host-microbiota interactions at barrier sites and beyond. Trends Mol Med. 2015;21:233–44.CrossRefPubMed
9.
Turnbaugh PJ, Ridaura VK, Faith JJ, Rey FE, Knight R, Gordon JI. The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci Transl Med. 2009;1:6ra14.CrossRefPubMedPubMedCentral
10.
Jernberg C, Lofmark S, Edlund C, Jansson JK. Long-term impacts of antibiotic exposure on the human intestinal microbiota. Microbiology. 2010;156:3216–23.CrossRefPubMed
11.
Tejesvi MV, Arvonen M, Kangas SM, Keskitalo PL, Pirttila AM, Karttunen TJ, et al. Faecal microbiome in new-onset juvenile idiopathic arthritis. Eur J Clin Microbiol Infect Dis. 2016;35:363–70.CrossRefPubMed
12.
Arvonen M, Virta LJ, Pokka T, Kroger L, Vahasalo P. Repeated exposure to antibiotics in infancy: a predisposing factor for juvenile idiopathic arthritis or a sign of this group's greater susceptibility to infections? J Rheumatol. 2015;42:521–6.CrossRefPubMed
13.
Horton DB, Scott FI, Haynes K, Putt ME, Rose CD, Lewis JD, et al. Antibiotic exposure and juvenile idiopathic arthritis: a case-control study. Pediatrics. 2015;136:e333–43.CrossRefPubMedPubMedCentral
14.
Prahalad S, Ryan MH, Shear ES, Thompson SD, Glass DN, Giannini EH. Twins concordant for juvenile rheumatoid arthritis. Arthritis Rheum. 2000;43:2611–2.CrossRefPubMed
15.
Glass DN, Giannini EH. Juvenile rheumatoid arthritis as a complex genetic trait. Arthritis Rheum. 1999;42:2261–8.CrossRefPubMed
16.
Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, et al. A core gut microbiome in obese and lean twins. Nature. 2009;457:480–4.CrossRefPubMed
17.
Hinks A, Cobb J, Marion MC, Prahalad S, Sudman M, Bowes J, et al. Dense genotyping of immune-related disease regions identifies 14 new susceptibility loci for juvenile idiopathic arthritis. Nat Genet. 2013;45:664–9.CrossRefPubMedPubMedCentral
18.
Rigante D, Bosco A, Esposito S. The Etiology of Juvenile Idiopathic Arthritis. Clin Rev Allergy Immunol. 2015;49:253–61.CrossRefPubMed
19.
Aslan M, Kasapcopur O, Yasar H, Polat E, Saribas S, Cakan H, et al. Do infections trigger juvenile idiopathic arthritis? Rheumatol Int. 2011;31:215–20.CrossRefPubMed
20.
Wedderburn LR, Robinson N, Patel A, Varsani H, Woo P. Selective recruitment of polarized T cells expressing CCR5 and CXCR3 to the inflamed joints of children with juvenile idiopathic arthritis. Arthritis Rheum. 2000;43:765–74.CrossRefPubMed
21.
Nistala K, Moncrieffe H, Newton KR, Varsani H, Hunter P, Wedderburn LR. Interleukin-17-producing T cells are enriched in the joints of children with arthritis, but have a reciprocal relationship to regulatory T cell numbers. Arthritis Rheum. 2008;58:875–87.CrossRefPubMedPubMedCentral
22.
Cosmi L, Cimaz R, Maggi L, Santarlasci V, Capone M, Borriello F, et al. Evidence of the transient nature of the Th17 phenotype of CD4 + CD161+ T cells in the synovial fluid of patients with juvenile idiopathic arthritis. Arthritis Rheum. 2011;63:2504–15.CrossRefPubMed
23.
Grant CR, Liberal R, Mieli-Vergani G, Vergani D, Longhi MS. Regulatory T-cells in autoimmune diseases: challenges, controversies and--yet--unanswered questions. Autoimmun Rev. 2015;14:105–16.CrossRefPubMed
24.
Wehrens EJ, Mijnheer G, Duurland CL, Klein M, Meerding J, van Loosdregt J, et al. Functional human regulatory T cells fail to control autoimmune inflammation due to PKB/c-akt hyperactivation in effector cells. Blood. 2011;118:3538–48.CrossRefPubMed
25.
Huttenlocher A, Smith JA. Neutrophils in pediatric autoimmune disease. Curr Opin Rheumatol. 2015;27:500–4.CrossRefPubMed
26.
Piper C, Pesenacker AM, Bending D, Thirugnanabalan B, Varsani H, Wedderburn LR, et al. T cell expression of granulocyte-macrophage colony-stimulating factor in juvenile arthritis is contingent upon Th17 plasticity. Arthritis Rheumatol. 2014;66:1955–60.CrossRefPubMedPubMedCentral
27.
Li J, Jia H, Cai X, Zhong H, Feng Q, Sunagawa S, et al. An integrated catalog of reference genes in the human gut microbiome. Nat Biotechnol. 2014;32:834–41.CrossRefPubMed
28.
Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464:59–65.CrossRefPubMedPubMedCentral
29.
Belkaid Y, Hand TW. Role of the microbiota in immunity and inflammation. Cell. 2014;157:121–41.CrossRefPubMedPubMedCentral
30.
Palm NW, de Zoete MR, Flavell RA. Immune-microbiota interactions in health and disease. Clin Immunol. 2015;159:122–7.CrossRefPubMedPubMedCentral
31.
Natividad JM, Verdu EF. Modulation of intestinal barrier by intestinal microbiota: pathological and therapeutic implications. Pharmacol Res. 2013;69:42–51.CrossRefPubMed
32.
Pabst O, Herbrand H, Friedrichsen M, Velaga S, Dorsch M, Berhardt G, et al. Adaptation of solitary intestinal lymphoid tissue in response to microbiota and chemokine receptor CCR7 signaling. J Immunol. 2006;177:6824–32.CrossRefPubMed
33.
Bouskra D, Brezillon C, Berard M, Werts C, Varona R, Boneca IG, et al. Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis. Nature. 2008;456:507–10.CrossRefPubMed
34.
Ivanov II, Frutos Rde L, Manel N, Yoshinaga K, Rifkin DB, Sartor RB, et al. Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe. 2008;4:337–49.CrossRefPubMedPubMedCentral
35.
Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T, Karaoz U, et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell. 2009;139:485–98.CrossRefPubMedPubMedCentral
36.
Littman DR, Rudensky AY. Th17 and regulatory T cells in mediating and restraining inflammation. Cell. 2010;140:845–58.CrossRefPubMed
37.
Maynard CL, Elson CO, Hatton RD, Weaver CT. Reciprocal interactions of the intestinal microbiota and immune system. Nature. 2012;489:231–41.CrossRefPubMedPubMedCentral
38.
Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T, Momose Y, et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science. 2011;331:337–41.CrossRefPubMed
39.
Furusawa Y, Obata Y, Fukuda S, Endo TA, Nakato G, Takahashi D, et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature. 2013;504:446–50.CrossRefPubMed
40.
Miossec P, Korn T, Kuchroo VK. Interleukin-17 and type 17 helper T cells. N Engl J Med. 2009;361:888–98.CrossRefPubMed
41.
Rogier R, Koenders MI, Abdollahi-Roodsaz S. Toll-like receptor mediated modulation of T cell response by commensal intestinal microbiota as a trigger for autoimmune arthritis. J Immunol Res. 2015;2015:527696.CrossRefPubMedPubMedCentral
42.
Cusick MF, Libbey JE, Fujinami RS. Molecular mimicry as a mechanism of autoimmune disease. Clin Rev Allergy Immunol. 2012;42:102–11.CrossRefPubMedPubMedCentral
43.
Goldstein I, Rebeyrotte P, Parlebas J, Halpern B. Isolation from heart valves of glycopeptides which share immunological properties with Streptococcus haemolyticus group A polysaccharides. Nature. 1968;219:866–8.CrossRefPubMed
44.
Wucherpfennig KW, Strominger JL. Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell. 1995;80:695–705.CrossRefPubMed
45.
Su LF, Kidd BA, Han A, Kotzin JJ, Davis MM. Virus-specific CD4(+) memory-phenotype T cells are abundant in unexposed adults. Immunity. 2013;38:373–83.CrossRefPubMedPubMedCentral
46.
Hand TW, Dos Santos LM, Bouladoux N, Molloy MJ, Pagan AJ, Pepper M, et al. Acute gastrointestinal infection induces long-lived microbiota-specific T cell responses. Science. 2012;337:1553–6.CrossRefPubMedPubMedCentral
47.
Kuhn KA, Pedraza I, Demoruelle MK. Mucosal immune responses to microbiota in the development of autoimmune disease. Rheum Dis Clin North Am. 2014;40:711–25.CrossRefPubMed
48.
Horwitz MS, Bradley LM, Harbertson J, Krahl T, Lee J, Sarvetnick N. Diabetes induced by Coxsackie virus: initiation by bystander damage and not molecular mimicry. Nat Med. 1998;4:781–5.CrossRefPubMed
49.
Vanderlugt CL, Miller SD. Epitope spreading in immune-mediated diseases: implications for immunotherapy. Nat Rev Immunol. 2002;2:85–95.CrossRefPubMed
50.
Miller SD, Vanderlugt CL, Begolka WS, Pao W, Yauch RL, Neville KL, et al. Persistent infection with Theiler's virus leads to CNS autoimmunity via epitope spreading. Nat Med. 1997;3:1133–6.CrossRefPubMed
51.
Wegner N, Wait R, Sroka A, Eick S, Nguyen KA, Lundberg K, et al. Peptidylarginine deiminase from Porphyromonas gingivalis citrullinates human fibrinogen and alpha-enolase: implications for autoimmunity in rheumatoid arthritis. Arthritis Rheum. 2010;62:2662–72.CrossRefPubMedPubMedCentral
52.
Stoll ML, Kumar R, Morrow CD, Lefkowitz EJ, Cui X, Genin A, et al. Altered microbiota associated with abnormal humoral immune responses to commensal organisms in enthesitis-related arthritis. Arthritis Res Ther. 2014;16:486.CrossRefPubMedPubMedCentral
53.
Gill T, Asquith M, Rosenbaum JT, Colbert RA. The intestinal microbiome in spondyloarthritis. Curr Opin Rheumatol. 2015;27:319–25.CrossRefPubMedPubMedCentral
54.
Malin M, Verronen P, Mykkanen H, Salminen S, Isolauri E. Increased bacterial urease activity in faeces in juvenile chronic arthritis: evidence of altered intestinal microflora? Br J Rheumatol. 1996;35:689–94.CrossRefPubMed
55.
Malin M, Verronen P, Korhonen H, Syvaoja EL, Salminen S, Mykkanen H, et al. Dietary therapy with Lactobacillus GG, bovine colostrum or bovine immune colostrum in patients with juvenile chronic arthritis: evaluation of effect on gut defence mechanisms. Inflammopharmacology. 1997;5:219–36.CrossRefPubMed
56.
Picco P, Gattorno M, Marchese N, Vignola S, Sormani MP, Barabino A, et al. Increased gut permeability in juvenile chronic arthritides. A multivariate analysis of the diagnostic parameters. Clin Exp Rheumatol. 2000;18:773–8.PubMed
57.
Hissink Muller P, Westedt P, Budding A, Allaart C, Brinkman D, Kuijpers T, et al. PReS-FINAL-2160: Intestinal microbiome in polyarticular juvenile idiopathic arthritis: a pilot study. Pediatr Rheumatol. 2013;11 Suppl 2:P172.CrossRef
58.
Gibson MK, Crofts TS, Dantas G. Antibiotics and the developing infant gut microbiota and resistome. Curr Opin Microbiol. 2015;27:51–6.CrossRefPubMed
59.
Sullivan A, Edlund C, Nord CE. Effect of antimicrobial agents on the ecological balance of human microflora. Lancet Infect Dis. 2001;1:101–14.CrossRefPubMed
60.
Lofmark S, Jernberg C, Jansson JK, Edlund C. Clindamycin-induced enrichment and long-term persistence of resistant Bacteroides spp. and resistance genes. J Antimicrob Chemother. 2006;58:1160–7.CrossRefPubMed
61.
Round JL, Lee SM, Li J, Tran G, Jabri B, Chatila TA, et al. The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota. Science. 2011;332:974–7.CrossRefPubMedPubMedCentral
62.
Perez-Cobas AE, Artacho A, Knecht H, Ferrus ML, Friedrichs A, Ott SJ, et al. Differential effects of antibiotic therapy on the structure and function of human gut microbiota. PLoS ONE. 2013;8:e80201.CrossRefPubMedPubMedCentral
63.
Sawhney S, Magalhaes CS. Paediatric rheumatology--a global perspective. Best Pract Res Clin Rheumatol. 2006;20:201–21.CrossRefPubMed
64.
Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, et al. Human gut microbiome viewed across age and geography. Nature. 2012;486:222–7.PubMedPubMedCentral
65.
Scher JU, Littman DR, Abramson SB. Microbiome in Inflammatory Arthritis and Human Rheumatic Diseases. Arthritis Rheumatol. 2016;68:35–45.CrossRefPubMed
66.
Shi Y, Dong Y, Huang W, Zhu D, Mao H, Su P. Fecal Microbiota Transplantation for Ulcerative Colitis: A Systematic Review and Meta-Analysis. PLoS ONE. 2016;11:e0157259.CrossRefPubMedPubMedCentral
67.
Bakken JS, Borody T, Brandt LJ, Brill JV, Demarco DC, Franzos MA, et al. Treating Clostridium difficile infection with fecal microbiota transplantation. Clin Gastroenterol Hepatol. 2011;9:1044–9.CrossRefPubMedPubMedCentral
68.
Li M, Liang P, Li Z, Wang Y, Zhang G, Gao H, et al. Fecal microbiota transplantation and bacterial consortium transplantation have comparable effects on the re-establishment of mucosal barrier function in mice with intestinal dysbiosis. Front Microbiol. 2015;6:692.PubMedPubMedCentral
69.
Lawley TD, Clare S, Walker AW, Stares MD, Connor TR, Raisen C, et al. Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice. PLoS Pathog. 2012;8:e1002995.CrossRefPubMedPubMedCentral