Advertisement

Der Internist

, Volume 58, Issue 5, pp 449–455 | Cite as

Mikrobiom und Autoimmunität

  • T. Schröder
  • S. Ibrahim
Schwerpunkt: Mikrobiom

Zusammenfassung

Das Mikrobiom stellt eine wesentliche funktionelle Komponente an der Grenzfläche zwischen Umwelt und Organismus dar. Störungen der Integrität und des mikrobiellen Gleichgewichts beeinflussen verschiedene gesundheitsrelevante Prozesse, darunter auch die Autoimmunität. In der Darmschleimhaut findet eine besonders aktive Interaktion zwischen Wirt und Mikroorganismen statt. Eine zunehmende Menge wissenschaftlicher Daten hilft dabei zu verstehen, wie die Zusammensetzung und die Funktionalität des Mikrobioms die intestinale Barrierefunktion und darüber hinaus pro- und antiinflammatorische Immunmechanismen an auch weiter entfernten Organen regulieren. Neben dem intestinalen Mikrobiom hat auch das lokale Mikrobiom der Haut eine funktionelle Bedeutung für verschiedene Krankheitsprozesse. Dieser Übersichtsbeitrag geht auf die Bedeutung des Mikrobioms für das lokale und systemische Immunsystem ein. Dabei wird auch beschrieben, wie eine gestörte Interaktion zwischen Mikrobiom und Wirt die Entstehung und Progression von Autoimmunerkrankungen beeinflusst. Das Verständnis dieser Zusammenhänge wird neue diagnostische und therapeutische Ansätze erschließen.

Schlüsselwörter

Rheumatoide Arthritis Multiple Sklerose Diabetes mellitus Typ 1 Systemischer Lupus erythematodes Autoimmune Hauterkrankungen 

The microbiome and autoimmunity

Abstract

An abundant and diverse set of commensal microbial communities covers the body’s surfaces, collectively so-called microbiome. It has a functional impact on various immune processes and modulates many health-related processes, including autoimmunity. An active site of microorganism–host interplay is the intestinal mucosa. Growing evidence has helped us to learn how a specific microbiota composition and its functionality determine the intestinal barrier function and, furthermore, modulate pro-inflammatory and anti-inflammatory immune mechanisms in remote organs. In addition, the microbial composition of the skin is important for the functionality of the skin barrier and autoimmune skin diseases. Here, we review the importance of the microbiome for the local and systemic immune system and how a disturbed microbiome–host interaction can affect the development and progression of autoimmune diseases. Understanding these associations will help to unravel new diagnostic and therapeutic approaches for those diseases.

Keywords

Arthritis, rheumatoid Multiple sclerosis Diabetes mellitus, type 1 Lupus erythematosus, systemic Autoimmune diseases, skin 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt

T. Schröder und S. Ibrahim geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

Literatur

  1. 1.
    Al-Asmakh M, Zadjali F (2015) Use of germ-free animal models in microbiota-related research. J Microbiol Biotechnol 25:1583–1588. doi: 10.4014/jmb.1501.01039 CrossRefPubMedGoogle Scholar
  2. 2.
    Andréasson K, Alrawi Z, Persson A et al (2016) Intestinal dysbiosis is common in systemic sclerosis and associated with gastrointestinal and extraintestinal features of disease. Arthritis Res Ther 18:278. doi: 10.1186/s13075-016-1182-z CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Atarashi K, Tanoue T, Ando M et al (2015) Th17 cell induction by adhesion of microbes to intestinal epithelial cells. Cell 163:367–380. doi: 10.1161/CIRCRESAHA.116.303790.The CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Berer K, Mues M, Koutrolos M et al (2011) Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature 479:538–541. doi: 10.1038/nature10554 CrossRefPubMedGoogle Scholar
  5. 5.
    Carvalho FA, Koren O, Goodrich JK et al (2012) Transient Inability to manage Proteobacteria promotes chronic gut inflammation in TLR5-deficient mice. Cell Host Microbe 12:139–152. doi: 10.1016/j.chom.2012.07.004.Transient CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Cogen AL, Nizet V, Gallo RL (2008) Skin microbiota: a source of disease or defence? Br J Dermatol 158:442–455. doi: 10.1111/j.1365-2133.2008.08437.x CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Costello EEK, Lauber CCL, Hamady M et al (2009) Bacterial community variation in human body habitats across space and time. Science 326:1694–1697. doi: 10.1126/science.1177486.Bacterial CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Dominguez-Bello MG, Costello EK, Contreras M et al (2010) Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci U S A 107:11971–11975. doi: 10.1073/pnas.1002601107 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Elenberg Y, Shaoul R (2014) The role of infant nutrition in the prevention of future disease. Front Pediatr 2:73. doi: 10.3389/fped.2014.00073 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Ellebrecht CT, Srinivas G, Bieber K et al (2016) Skin microbiota-associated inflammation precedes autoantibody induced tissue damage in experimental epidermolysis bullosa acquisita. J Autoimmun 68:14–22. doi: 10.1016/j.jaut.2015.08.007 CrossRefPubMedGoogle Scholar
  11. 11.
    da Fonseca DM, Hand TW, Han S‑J et al (2015) Microbiota-dependent sequelae of acute infection compromise tissue-specific immunity. Cell 163:3–14. doi: 10.1016/j.addr.2015.05.001.An CrossRefGoogle Scholar
  12. 12.
    Gao Z, Tseng CH, Strober BE et al (2008) Substantial alterations of the cutaneous bacterial biota in psoriatic lesions. PLOS ONE. doi: 10.1371/journal.pone.0002719 Google Scholar
  13. 13.
    Grice E, Kong HH, Conlan S et al (2009) Topographical and temporal diversity of the human skin. Science 324(80):1190–1192. doi: 10.1126/science.1171700 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Haghikia A, Jörg S, Duscha A et al (2016) Dietary fatty acids directly impact central nervous system autoimmunity via the small intestine. Immunity 44:951–953. doi: 10.1016/j.immuni.2016.04.006 CrossRefPubMedGoogle Scholar
  15. 15.
    He B, Hoang TK, Wang T et al (2016) Resetting microbiota by Lactobacillus reuteri inhibits T reg deficiency-induced autoimmunity via adenosine A2A receptors. J Exp Med:1–17. doi: 10.1084/jem.20160961 Google Scholar
  16. 16.
    Hevia A, Milani C, López P et al (2014) Intestinal dysbiosis associated with systemic lupus erythematosus. MBio 5:1–10. doi: 10.1128/mBio.01548-14.Invited CrossRefGoogle Scholar
  17. 17.
    Hitchon CA, Chandad F, Ferucci ED et al (2010) Antibodies to porphyromonas gingivalis are associated with anticitrullinated protein antibodies in patients with rheumatoid arthritis and their relatives. J Rheumatol 37:1105CrossRefPubMedGoogle Scholar
  18. 18.
    Honda K, Littman DR (2016) The microbiota in adaptive immune homeostasis and disease. Nature 535:75–84. doi: 10.1038/nature18848 CrossRefPubMedGoogle Scholar
  19. 19.
    Jangi S, Gandhi R, Cox LM et al (2016) Alterations of the human gut microbiome in multiple sclerosis. Nat Commun 7:12015. doi: 10.1038/ncomms12015 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Khosravi A, Yáñez A, Price JG et al (2014) Gut microbiota promotes hematopoiesis to control bacterial infection. Cell Host Microbe 15:374–381. doi: 10.1016/j.chom.2014.02.006.Gut CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Kimpimäki T, Kupila A, Hämäläinen AM et al (2001) The first signs of β‑cell autoimmunity appear in infancy in genetically susceptible children from the general population: the finnish type 1 diabetes prediction and prevention study. J Clin Endocrinol Metab 86:4782–4788. doi: 10.1210/jc.86.10.4782 PubMedGoogle Scholar
  22. 22.
    Kostic AD, Gevers D, Siljander H et al (2015) The dynamics of the human infant gut microbiome in development and in progression towards type 1 diabetes. Cell Host Microbe 17:260–273. doi: 10.1016/j.chom.2015.01.001.The CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Kriegel MA, Sefik E, Hill JA et al (2011) Naturally transmitted segmented filamentous bacteria segregate with diabetes protection in nonobese diabetic mice. Proc Natl Acad Sci U S A 108:11548–11553. doi: 10.1073/pnas.1108924108 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Lee YK, Menezes JS, Umesaki Y, Mazmanian SK (2011) Proinflammatory T‑cell responses to gut microbiota promote experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A 108(Suppl):4615–4622. doi: 10.1073/pnas.1000082107 CrossRefPubMedGoogle Scholar
  25. 25.
    Ley RE, Peterson DA, Gordon JI (2006) Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 124:837–848. doi: 10.1016/j.cell.2006.02.017 CrossRefPubMedGoogle Scholar
  26. 26.
    Mansson I, Colldahl H (1965) The intestinal flora in patients with bronchial asthma and rheumatoid arthritis. Acta Allergol 20:94–104CrossRefGoogle Scholar
  27. 27.
    Matamoros S, Gras-Leguen C, Le Vacon F et al (2013) Development of intestinal microbiota in infants and its impact on health. Trends Microbiol 21:167–173. doi: 10.1016/j.tim.2012.12.001 CrossRefPubMedGoogle Scholar
  28. 28.
    Olszak T, An D, Zeissig S et al (2012) Microbial exposure during early life has persistent effects on natural killer T cell function. Science 336(80):489–493. doi: 10.1126/science.1219328.Microbial CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Parikka V, Näntö-Salonen K, Saarinen M et al (2012) Early Seroconversion and rapidly increasing autoantibody concentrations predict prepubertal manifestation of type 1 diabetes in Children at genetic risk. Diabetologia 55:1926–1936. doi: 10.1007/s00125-012-2523-3 CrossRefPubMedGoogle Scholar
  30. 30.
    Peterson DA, McNulty NP, Guruge JL, Gordon JI (2007) IgA response to symbiotic bacteria as a mediator of gut homeostasis. Cell Host Microbe 2:328–339. doi: 10.1016/j.chom.2007.09.013 CrossRefPubMedGoogle Scholar
  31. 31.
    Rojo D, Hevia A, Bargiela R et al (2015) Ranking the impact of human health disorders on gut metabolism: systemic lupus erythematosus and obesity as study cases. Sci Rep 5:8310. doi: 10.1038/srep08310 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Russell SL, Gold MJ, Hartmann M et al (2012) Early life antibiotic-driven changes in microbiota enhance susceptibility to allergic asthma. EMBO Rep 13:440–447. doi: 10.1038/embor.2012.32 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Scher JU, Sczesnak A, Longman RS et al (2013) Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. Elife 2:e01202. doi: 10.7554/eLife.01202 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Sonnenberg GF, Monticelli LA, Alenghat T et al (2012) Innate lymphoid cells promote anatomical containment of lymphoid-resident commensal bacteria. Science 336:1321–1325. doi: 10.1126/science.1222551.Innate CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Srinivas G, Möller S, Wang J et al (2013) Genome-wide mapping of gene-microbiota interactions in susceptibility to autoimmune skin blistering. Nat Commun 4:2462. doi: 10.1038/ncomms3462 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Teng F, Klinger CN, Felix KM et al (2016) Gut microbiota drive autoimmune arthritis by promoting differentiation and migration of Peyer’s patch T follicular helper cells. Immunity 44:875–888. doi: 10.1016/j.immuni.2016.03.013 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Thaiss CA, Zmora N, Levy M, Elinav E (2016) The microbiome and innate immunity. Nature 535:65–74. doi: 10.1038/nature18847 CrossRefPubMedGoogle Scholar
  38. 38.
    Vossenkamper A, Blair PA, Safinia N et al (2013) A role for gut-associated lymphoid tissue in shaping the human B cell repertoire. J Exp Med 210:1665–1674. doi: 10.1084/Jem.20122465 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Van de Wiele T, Van Praet JT, Marzorati M et al (2016) How the microbiota shapes rheumatic diseases. Nat Rev Rheumatol 12:398–411. doi: 10.1038/nrrheum.2016.85 CrossRefPubMedGoogle Scholar
  40. 40.
    Wu HJ, Ivanov II, Darce J et al (2010) Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity 32:815–827. doi: 10.1016/j.immuni.2010.06.001 CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Zheng W, Zhang Z, Liu C et al (2015) Metagenomic sequencing reveals altered metabolic pathways in the oral microbiota of sailors during a long sea voyage. Sci Rep 5:1–11. doi: 10.1038/srep09131 Google Scholar

Copyright information

© Springer Medizin Verlag GmbH 2017

Authors and Affiliations

  1. 1.Institut für ErnährungsmedizinUniversitätsklinikum Schleswig-Holstein, Campus LübeckLübeckDeutschland
  2. 2.Medizinische Klinik 1Universitätsklinikum Schleswig-Holstein, Campus LübeckLübeckDeutschland
  3. 3.Institut für systemische EntzündungsforschungUniversität zu LübeckLübeckDeutschland
  4. 4.Institut für experimentelle DermatologieUniversität zu LübeckLübeckDeutschland

Personalised recommendations