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22-07-2016 | Juvenile idiopathic arthritis | Review | Article

Gut microbiota-host interactions and juvenile idiopathic arthritis

Journal: Pediatric Rheumatology

Authors: Miika Arvonen, Lillemor Berntson, Tytti Pokka, Tuomo J Karttunen, Paula Vähäsalo, Matthew L Stoll

Publisher: BioMed Central

Abstract

Background

Juvenile idiopathic arthritis is the most common form of chronic arthritis in children. There is mounting evidence that the microbiota may influence the disease.

Main body

Recent observations in several systemic inflammatory diseases including JIA have indicated that abnormalities in the contents of the microbiota may be factors in disease pathogenesis, while other studies in turn have shown that environmental factors impacting the composition of the microbiota, such as delivery mode and early exposure to antibiotics, affect the risk of chronic inflammatory diseases including JIA. Microbial alterations may predispose to JIA through a variety of mechanisms, including impaired immunologic development, alterations in the balances of pro- versus anti-inflammatory bacteria, and low-grade mucosal inflammation. Additional confirmatory studies of microbiota aberrations and their risk factors are needed, as well as additional mechanistic studies linking these alterations to the disease itself.

Conclusions

The microbiota may influence the risk of JIA and other systemic inflammatory conditions through a variety of mechanisms. Additional research is required to improve our understanding of the links between the microbiota and arthritis, and the treatment implications thereof.

Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, et al. International league of associations for rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004;31(2):390–2.PubMed

Langendijk PS, Schut F, Jansen GJ, Raangs GC, Kamphuis GR, Wilkinson MH, et al. Quantitative fluorescence in situ hybridization of Bifidobacterium spp. with genus-specific 16S rRNA-targeted probes and its application in fecal samples. Appl Environ Microbiol. 1995;61(8):3069–75.PubMedPubMedCentral

Franzosa EA, Hsu T, Sirota-Madi A, Shafquat A, Abu-Ali G, Morgan XC, et al. Sequencing and beyond: integrating molecular ‘omics’ for microbial community profiling. Nat Rev Microbiol. 2015;13(6):360–72.CrossRefPubMedPubMedCentral

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(3):363–70.CrossRefPubMed

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(1):82–91.CrossRefPubMed

Murri M, Leiva I, Gomez-Zumaquero JM, Tinahones FJ, Cardona F, Soriguer F, et al. Gut microbiota in children with type 1 diabetes differs from that in healthy children: a case–control study. BMC Med 2013 Feb 21;11:46-7015-11-46.

Davis-Richardson AG, Ardissone AN, Dias R, Simell V, Leonard MT, Kemppainen KM, et al. Bacteroides dorei dominates gut microbiome prior to autoimmunity in Finnish children at high risk for type 1 diabetes. Front Microbiol. 2014;5:678.CrossRefPubMedPubMedCentral

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(6):486. -014-0486-0.

Cao Y, Shen J, Ran ZH. Association between Faecalibacterium prausnitzii reduction and inflammatory bowel disease: a meta-analysis and systematic review of the literature. Gastroenterol Res Pract. 2014;2014:872725.PubMedPubMedCentral

10.

Koenig JE, Spor A, Scalfone N, Fricker AD, Stombaugh J, Knight R, et al. Succession of microbial consortia in the developing infant gut microbiome. Proc Natl Acad Sci U S A. 2011;108 Suppl 1:4578–85.CrossRefPubMed

11.

Bates JM, Mittge E, Kuhlman J, Baden KN, Cheesman SE, Guillemin K. Distinct signals from the microbiota promote different aspects of zebrafish gut differentiation. Dev Biol. 2006;297(2):374–86.CrossRefPubMed

12.

Hooper LV, Wong MH, Thelin A, Hansson L, Falk PG, Gordon JI. Molecular analysis of commensal host-microbial relationships in the intestine. Science. 2001;291(5505):881–4.CrossRefPubMed

13.

Rautava S, Luoto R, Salminen S, Isolauri E. Microbial contact during pregnancy, intestinal colonization and human disease. Nat Rev Gastroenterol Hepatol. 2012;9(10):565–76.CrossRefPubMed

14.

Biasucci G, Rubini M, Riboni S, Morelli L, Bessi E, Retetangos C. Mode of delivery affects the bacterial community in the newborn gut. Early Hum Dev. 2010;86 Suppl 1:13–5.CrossRefPubMed

15.

Huurre A, Kalliomaki M, Rautava S, Rinne M, Salminen S, Isolauri E. Mode of delivery - effects on gut microbiota and humoral immunity. Neonatology. 2008;93(4):236–40.CrossRefPubMed

16.

Salminen S, Gibson GR, McCartney AL, Isolauri E. Influence of mode of delivery on gut microbiota composition in seven year old children. Gut. 2004;53(9):1388–9.CrossRefPubMedPubMedCentral

17.

Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G, Fierer N, et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci U S A. 2010;107(26):11971–5.CrossRefPubMedPubMedCentral

18.

Collado MC, Rautava S, Isolauri E, Salminen S. Gut microbiota: a source of novel tools to reduce the risk of human disease? Pediatr Res. 2015;77(1–2):182–8.CrossRefPubMed

19.

Carlens C, Jacobsson L, Brandt L, Cnattingius S, Stephansson O, Askling J. Perinatal characteristics, early life infections and later risk of rheumatoid arthritis and juvenile idiopathic arthritis. Ann Rheum Dis. 2009;68(7):1159–64.CrossRefPubMed

20.

Kristensen K, Henriksen L. Cesarean section and disease associated with immune function. J Allergy Clin Immunol. 2015;11.

21.

Harmsen HJ, Wildeboer-Veloo AC, Raangs GC, Wagendorp AA, Klijn N, Bindels JG, et al. Analysis of intestinal flora development in breast-fed and formula-fed infants by using molecular identification and detection methods. J Pediatr Gastroenterol Nutr. 2000;30(1):61–7.CrossRefPubMed

22.

Montoya J, Matta NB, Suchon P, Guzian MC, Lambert NC, Mattei JP, et al. Patients with ankylosing spondylitis have been breast fed less often than healthy controls: a case–control retrospective study. Ann Rheum Dis. 2015;12.

23.

Virtanen SM, Rasanen L, Aro A, Lindstrom J, Sippola H, Lounamaa R, et al. Infant feeding in Finnish children less than 7 yr of age with newly diagnosed IDDM. Childhood diabetes in Finland study group. Diabetes Care. 1991;14(5):415–7.CrossRefPubMed

24.

Mason T, Rabinovich CE, Fredrickson DD, Amoroso K, Reed AM, Stein LD, et al. Breast feeding and the development of juvenile rheumatoid arthritis. J Rheumatol. 1995;22(6):1166–70.PubMed

25.

Rosenberg AM. Evaluation of associations between breast feeding and subsequent development of juvenile rheumatoid arthritis. J Rheumatol. 1996;23(6):1080–2.PubMed

26.

Kasapcopur O, Tasdan Y, Apelyan M, Akkus S, Caliskan S, Sever L, et al. Does breast feeding prevent the development of juvenile rheumatoid arthritis? J Rheumatol. 1998;25(11):2286–7.PubMed

27.

Jernberg C, Lofmark S, Edlund C, Jansson JK. Long-term ecological impacts of antibiotic administration on the human intestinal microbiota. ISME J. 2007;1(1):56–66.CrossRefPubMed

28.

Dethlefsen L, Relman DA. Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc Natl Acad Sci U S A. 2011;108 Suppl 1:4554–61.CrossRefPubMed

29.

Korpela K, Salonen A, Virta LJ, Kekkonen RA, Forslund K, Bork P, et al. Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children. Nat Commun. 2016;7:10410.CrossRefPubMedPubMedCentral

30.

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(2):e333–43.CrossRefPubMed

31.

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(3):521–6.CrossRefPubMed

32.

Scher JU, Sczesnak A, Longman RS, Segata N, Ubeda C, Bielski C, et al. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. Elife. 2013;2, e01202.CrossRefPubMedPubMedCentral

33.

Segain JP. Raingeard de la Bletiere D, Bourreille A, Leray V, Gervois N, Rosales C, et al. Butyrate inhibits inflammatory responses through NFkappaB inhibition: implications for Crohn's disease. Gut. 2000;47(3):397–403.CrossRefPubMedPubMedCentral

34.

Sokol H, Pigneur B, Watterlot L, Lakhdari O, Bermudez-Humaran LG, Gratadoux JJ, et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci U S A. 2008;105(43):16731–6.CrossRefPubMedPubMedCentral

35.

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(7480):446–50.CrossRefPubMed

36.

Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J, DeRoos P, et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature. 2013;504(7480):451–5.CrossRefPubMedPubMedCentral

37.

Rath HC, Herfarth HH, Ikeda JS, Grenther WB, Hamm Jr TE, Balish E, et al. Normal luminal bacteria, especially Bacteroides species, mediate chronic colitis, gastritis, and arthritis in HLA-B27/human beta2 microglobulin transgenic rats. J Clin Invest. 1996;98(4):945–53.CrossRefPubMedPubMedCentral

38.

Sinkorova Z, Capkova J, Niederlova J, Stepankova R, Sinkora J. Commensal intestinal bacterial strains trigger ankylosing enthesopathy of the ankle in inbred B10.BR (H-2(k)) male mice. Hum Immunol. 2008;69(12):845–50.CrossRefPubMed

39.

Zhang X, Zhang D, Jia H, Feng Q, Wang D, Liang D, et al. The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat Med. 2015;21(8):895–905.CrossRefPubMed

40.

Berntson L, Agback P, Dicksved J. Changes in fecal microbiota and metabolomics in a child with juvenile idiopathic arthritis (JIA) responding to two treatment periods with exclusive enteral nutrition (EEN). Clin Rheumatol. 2016;35(6):1501–6.CrossRefPubMed

41.

Kolho KL, Korpela K, Jaakkola T, Pichai MV, Zoetendal EG, Salonen A, et al. Fecal microbiota in pediatric inflammatory bowel disease and its relation to inflammation. Am J Gastroenterol. 2015;110(6):921–30.CrossRefPubMed

42.

Ramanan D, Bowcutt R, Lee SC, Tang MS, Kurtz ZD, Ding Y, et al. Helminth infection promotes colonization resistance via type 2 immunity. Science. 2016;352(6285):608–12.CrossRefPubMedPubMedCentral

43.

Bashi T, Shovman O, Fridkin M, Volkov A, Barshack I, Blank M, et al. Novel therapeutic compound tuftsin-phosphorylcholine attenuates collagen-induced arthritis. Clin Exp Immunol. 2016;184(1):19–28.CrossRefPubMed

44.

Garg SK, Croft AM, Bager P. Helminth therapy (worms) for induction of remission in inflammatory bowel disease. Cochrane Database Syst Rev. 2014;1:CD009400. (1):CD009400.

45.

Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol. 2009;9(5):313–23.CrossRefPubMedPubMedCentral

46.

Gensollen T, Iyer SS, Kasper DL, Blumberg RS. How colonization by microbiota in early life shapes the immune system. Science. 2016;352(6285):539–44.CrossRefPubMed

47.

Cahenzli J, Koller Y, Wyss M, Geuking MB, McCoy KD. Intestinal microbial diversity during early-life colonization shapes long-term IgE levels. Cell Host Microbe. 2013;14(5):559–70.CrossRefPubMedPubMedCentral

48.

Rook GA. Hygiene hypothesis and autoimmune diseases. Clin Rev Allergy Immunol. 2012;42(1):5–15.CrossRefPubMed

49.

Olszak T, An D, Zeissig S, Vera MP, Richter J, Franke A, et al. Microbial exposure during early life has persistent effects on natural killer T cell function. Science. 2012;336(6080):489–93.CrossRefPubMedPubMedCentral

50.

Stoll ML. Gut microbes, immunity, and spondyloarthritis. Clin Immunol. 2015;159(2):134–42.CrossRefPubMed

51.

Stebbings S, Munro K, Simon MA, Tannock G, Highton J, Harmsen H, et al. Comparison of the faecal microflora of patients with ankylosing spondylitis and controls using molecular methods of analysis. Rheumatology (Oxford). 2002;41(12):1395–401.CrossRef

52.

Vatanen T, Kostic AD, D’Hennezel E, Siljander H, Franzosa EA, Yassour M, et al. Variation in microbiome LPS immunogenicity contributes to autoimmunity in humans. Cell. 2016;165(4):842–53.CrossRefPubMed

53.

Targan SR, Landers CJ, Yang H, Lodes MJ, Cong Y, Papadakis KA, et al. Antibodies to CBir1 flagellin define a unique response that is associated independently with complicated Crohn’s disease. Gastroenterology. 2005;128(7):2020–8.CrossRefPubMed

54.

Singh YP, Singh AK, Aggarwal A, Misra R. Evidence of cellular immune response to outer membrane protein of Salmonella typhimurium in patients with enthesitis-related arthritis subtype of juvenile idiopathic arthritis. J Rheumatol. 2011;38(1):161–6.CrossRefPubMed

55.

Lange L, Thiele GM, McCracken C, Wang G, Ponder LA, Angeles-Han ST, et al. Symptoms of periodontitis and antibody responses to Porphyromonas gingivalis in juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 2016;14(1):8. -016-0068-6.

56.

Hitchon CA, Chandad F, Ferucci ED, Willemze A, Ioan-Facsinay A, van der Woude D, et al. Antibodies to porphyromonas gingivalis are associated with anticitrullinated protein antibodies in patients with rheumatoid arthritis and their relatives. J Rheumatol. 2010;37(6):1105–12.CrossRefPubMed

57.

Feng T, Wang L, Schoeb TR, Elson CO, Cong Y. Microbiota innate stimulation is a prerequisite for T cell spontaneous proliferation and induction of experimental colitis. J Exp Med. 2010;207(6):1321–32.CrossRefPubMedPubMedCentral

58.

Breban M, Fernandez-Sueiro JL, Richardson JA, Hadavand RR, Maika SD, Hammer RE, et al. T cells, but not thymic exposure to HLA-B27, are required for the inflammatory disease of HLA-B27 transgenic rats. J Immunol. 1996;156(2):794–803.PubMed

59.

Taurog JD, Richardson JA, Croft JT, Simmons WA, Zhou M, Fernandez-Sueiro JL, et al. The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats. J Exp Med. 1994;180(6):2359–64.CrossRefPubMed

60.

Brandtzaeg P. Function of mucosa-associated lymphoid tissue in antibody formation. Immunol Invest. 2010;39(4–5):303–55.CrossRefPubMed

61.

Prindiville TP, Sheikh RA, Cohen SH, Tang YJ, Cantrell MC, Silva Jr J. Bacteroides fragilis enterotoxin gene sequences in patients with inflammatory bowel disease. Emerg Infect Dis. 2000;6(2):171–4.CrossRefPubMedPubMedCentral

62.

Tailford LE, Crost EH, Kavanaugh D, Juge N. Mucin glycan foraging in the human gut microbiome. Front Genet. 2015;6:81.CrossRefPubMedPubMedCentral

63.

Derrien M, Vaughan EE, Plugge CM, de Vos WM. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. Int J Syst Evol Microbiol. 2004;54(Pt 5):1469–76.CrossRefPubMed

64.

Martinez-Gonzalez O, Cantero-Hinojosa J, Paule-Sastre P, Gomez-Magan JC, Salvatierra-Rios D. Intestinal permeability in patients with ankylosing spondylitis and their healthy relatives. Br J Rheumatol. 1994;33(7):644–7.CrossRefPubMed

65.

Mielants H, Veys EM, Cuvelier C, De Vos M, Goemaere S, Maertens M, et al. Gut inflammation in children with late onset pauciarticular juvenile chronic arthritis and evolution to adult spondyloarthropathy--a prospective study. J Rheumatol. 1993;20:1567–72.PubMed

66.

Lionetti P, Pupi A, Veltroni M, Fonda C, Cavicchi MC, Azzari C, et al. Evidence of subclinical intestinal inflammation by 99m technetium leukocyte scintigraphy in patients with HLA-B27 positive juvenile onset active spondyloarthropathy. J Rheumatol. 2000;27:1538–41.PubMed

67.

Stoll ML, Punaro M, Patel AS. Fecal calprotectin in children with the enthesitis-related arthritis subtype of juvenile idiopathic arthritis. J Rheumatol. 2011;38(10):2274–5.CrossRefPubMedPubMedCentral

68.

Arvonen M, Vahasalo P, Turunen S, Salo HM, Maki M, Laurila K, et al. Altered expression of intestinal human leucocyte antigen D-related and immune signalling molecules in juvenile idiopathic arthritis. Clin Exp Immunol. 2012;170(3):266–73.CrossRefPubMedPubMedCentral

69.

Arvonen M, Ikni L, Augustin M, Karttunen TJ, Vahasalo P. Increase of duodenal and ileal mucosal cytotoxic lymphocytes in juvenile idiopathic arthritis. Clin Exp Rheumatol. 2010;28(1):128–34.PubMed

70.

Kokkonen J, Arvonen M, Vahasalo P, Karttunen TJ. Intestinal immune activation in juvenile idiopathic arthritis and connective tissue disease. Scand J Rheumatol. 2007;36(5):386–9.CrossRefPubMed

71.

Pichler J, Ong C, Shah N, Sebire N, Kiparrissi F, Borrelli O, et al. Histopathological features of gastrointestinal mucosal biopsies in children with Juvenile Idiopathic Arthritis. Pediatr Res. 2016;79(6):895–901.CrossRefPubMed

72.

De La Cochetiere MF, Durand T, Lepage P, Bourreille A, Galmiche JP, Dore J. Resilience of the dominant human fecal microbiota upon short-course antibiotic challenge. J Clin Microbiol. 2005;43:5588–92.CrossRef

73.

Dethlefsen L, Huse S, Sogin ML, Relman DA. The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biol. 2008;6, e280.CrossRefPubMedPubMedCentral

74.

Fouhy F, Guinane CM, Hussey S, Wall R, Ryan CA, Dempsey EM, et al. High-throughput sequencing reveals the incomplete, short-term recovery of infant gut microbiota following parenteral antibiotic treatment with ampicillin and gentamicin. Antimicrob Agents Chemother. 2012;56:5811–20.CrossRefPubMedPubMedCentral

75.

Jakobsson HE, Jernberg C, Andersson AF, Sjolund-Karlsson M, Jansson JK, Engstrand L. Short-term antibiotic treatment has differing long-term impacts on the human throat and gut microbiome. PLoS One. 2010;5, e9836.CrossRefPubMedPubMedCentral

76.

Lode H, Von der Hoh N, Ziege S, Borner K, Nord CE. Ecological effects of linezolid versus amoxicillin/clavulanic acid on the normal intestinal microflora. Scand J Infect Dis. 2001;33:899–903.CrossRefPubMed

77.

Mangin I, Leveque C, Magne F, Suau A, Pochart P. Long-term changes in human colonic Bifidobacterium populations induced by a 5-day oral amoxicillin-clavulanic acid treatment. PLoS One. 2012;7, e50257.CrossRefPubMedPubMedCentral

78.

Savino F, Roana J, Mandras N, Tarasco V, Locatelli E, Tullio V. Faecal microbiota in breast-fed infants after antibiotic therapy. Acta Paediatr. 2011;100:75–8.CrossRefPubMed

79.

Vervoort J, Xavier BB, Stewardson A, Coenen S, Godycki-Cwirko M, Adriaenssens N, et al. Metagenomic analysis of the impact of nitrofurantoin treatment on the human faecal microbiota. J Antimicrob Chemother. 2015;70:1989–92.PubMed

80.

Lee J, Gonzales-Navajas JM, Raz E. The “polarizing-tolerizing” mechanism of intestinal epithelium: its relevance to colonic homeostasis. Semin Immunopathol. 2008;30(1):3–9.CrossRefPubMed

81.

Hooper LV, Macpherson AJ. Immune adaptations that maintain homeostasis with the intestinal microbiota. Nat Rev Immunol. 2010;10(3):159–69.CrossRefPubMed

Medicine Matters Rheumatology

Abstract

Background

Main body

Conclusions