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Das Mikrobiom bei chronischen Erkrankungen

Darmbakterien bei chronisch-entzündlichen und Stoffwechselkrankheiten

Intestinal microbiome in chronic diseases

Relevance of gut bacteria in inflammatory bowel diseases and metabolic disorders

  • Leitthema
  • Published:
Der Diabetologe Aims and scope

Zusammenfassung

Hintergrund

Die intestinale Mikrobiota spielt in der Pathogenese chronisch-entzündlicher Darmerkrankungen, wie M. Crohn und Colitis ulcerosa, sowie metabolischer Krankheiten eine große Rolle.

Fragestellung

Es stellt sich die Frage, welche Rolle der Darm als Grenzfläche zwischen Bakterien und Wirtsfunktionen spielt.

Methoden

Aktuelle Forschungsergebnisse über die Funktion des Darms und Bakterien-Wirt-Interaktionen werden zusammengefasst und bewertet.

Ergebnisse und Diskussion

Bei zahlreichen Erkrankungen wurde ein Ungleichgewicht in der Zusammensetzung und Funktion der Mikrobiota im Darm (Dysbiose) nachgewiesen. Dysbiose in Kombination mit einem Funktionsverlust der immunologischen Grenzfläche im Darm wird als gemeinsames pathophysiologisches Merkmal für sowohl chronisch-entzündliche als auch metabolische Erkrankungen diskutiert. Die kausalen Zusammenhänge sind aufgrund fehlender prospektiver Studien und widersprüchlicher Daten allerdings nicht für alle Erkrankungen vollständig geklärt. Fäkaltransplantationen oder gezielte mikrobielle Therapien sind ein möglicher Ansatz, um chronische Erkrankungen zu behandeln, bedürfen aber der weiteren klinischen Validierung.

Abstract

Background

The intestinal microbiome plays an essential role in the development of chronic inflammatory diseases, such as inflammatory bowel disease (IBD) or metabolic disorders.

Objectives

What is the pathophysiological role of the intestine as an interface between bacterial and host functions?

Methods

Recent findings related to intestinal function and microbe–host interactions in the context of inflammatory and metabolic disorders are reviewed.

Results and conclusions

Changes in gut microbiota composition and function (dysbiosis) are associated with a variety of different pathologies. Dysbiosis in combination with the loss of gut barrier and immune functions are shared in inflammatory and metabolic disorders. Causal mechanisms for the interaction of dysbiotic microbial communities in the gut and disease onset require additional clinical and experimental validation including prospective cohort and gnotobiotic animal studies. Fecal microbiota transplantation and targeted microbial therapies are promising strategies for clinical intervention; however many questions need to be addressed including disease-specific selection of donor microbiota or synthetic bacterial consortia, application strategies and risk evaluation.

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Literatur

  1. Backhed F, Manchester JK, Semenkovich CF et al (2007) Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci USA 104:979–984

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Butto LF, Schaubeck M, Haller D (2015) Mechanisms of microbe-host interaction in Crohn’s disease: Dysbiosis vs. pathobiont selection. Front Immunol 6:555

    Article  PubMed  PubMed Central  Google Scholar 

  3. Cani PD, Bibiloni R, Knauf C et al (2008) Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 57:1470–1481

    Article  CAS  PubMed  Google Scholar 

  4. Cox LM, Yamanishi S, Sohn J et al (2014) Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell 158:705–721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Donath MY, Shoelson SE (2011) Type 2 diabetes as an inflammatory disease. Nat Rev Immunol 11:98–107

    Article  CAS  PubMed  Google Scholar 

  6. Feng Q, Liang S, Jia H et al (2015) Gut microbiome development along the colorectal adenoma-carcinoma sequence. Nat Commun 6:6528

    Article  CAS  PubMed  Google Scholar 

  7. Finucane MM, Sharpton TJ, Laurent TJ et al (2014) A taxonomic signature of obesity in the microbiome? Getting to the guts of the matter. PLOS ONE 9:e84689

    Article  PubMed  PubMed Central  Google Scholar 

  8. Fleissner CK, Huebel N, Abd El-Bary MM et al (2010) Absence of intestinal microbiota does not protect mice from diet-induced obesity. Br J Nutr 104:919–929

    Article  CAS  PubMed  Google Scholar 

  9. Forslund K, Hildebrand F, Nielsen T et al (2015) Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature 528:262–266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Frank DN, St Amand AL, Feldman RA et al (2007) Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci USA 104:13780–13785

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Gevers D, Kugathasan S, Denson LA et al (2014) The treatment-naive microbiome in new-onset Crohn’s disease. Cell Host Microbe 15:382–392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Gruber L, Kisling S, Lichti P et al (2013) High fat diet accelerates pathogenesis of murine Crohn’s disease-like ileitis independently of obesity. PLOS ONE 8:e71661

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Gummesson A, Carlsson LM, Storlien LH et al (2011) Intestinal permeability is associated with visceral adiposity in healthy women. Obesity 19:2280–2282

    Article  PubMed  Google Scholar 

  14. Haberman Y, Tickle TL, Dexheimer PJ et al (2014) Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature. J Clin Invest 124:3617–3633

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Harley IT, Giles DA, Pfluger PT et al (2013) Differential colonization with segmented filamentous bacteria and Lactobacillus murinus do not drive divergent development of diet-induced obesity in C57BL/6 mice. Mol Metab 2:171–183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hormannsperger G, Schaubeck M, Haller D (2015) Intestinal microbiota in animal models of inflammatory diseases. ILAR J 56:179–191

    Article  CAS  PubMed  Google Scholar 

  17. Horton F, Wright J, Smith L et al (2014) Increased intestinal permeability to oral chromium (51 Cr) –EDTA in human Type 2 diabetes. Diabet Med 31:559–563

    Article  CAS  PubMed  Google Scholar 

  18. Human Microbiome Project C (2012) Structure, function and diversity of the healthy human microbiome. Nature 486:207–214

    Article  Google Scholar 

  19. Joossens M, Huys G, Cnockaert M et al (2011) Dysbiosis of the faecal microbiota in patients with Crohn’s disease and their unaffected relatives. Gut 60:631–637

    Article  PubMed  Google Scholar 

  20. Jostins L, Ripke S, Weersma RK et al (2012) Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491:119–124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Karlsson FH, Tremaroli V, Nookaew I et al (2013) Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature 498:99–103

    Article  CAS  PubMed  Google Scholar 

  22. Kaser A, Zeissig S, Blumberg RS (2010) Inflammatory bowel disease. Annu Rev Immunol 28:573–621

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kassam Z, Lee CH, Yuan Y et al (2013) Fecal microbiota transplantation for Clostridium difficile infection: Systematic review and meta-analysis. Am J Gastroenterol 108:500–508

    Article  PubMed  Google Scholar 

  24. Kim SC, Tonkonogy SL, Albright CA et al (2005) Variable phenotypes of enterocolitis in interleukin 10-deficient mice monoassociated with two different commensal bacteria. Gastroenterology 128:891–906

    Article  CAS  PubMed  Google Scholar 

  25. Kless C, Muller VM, Schuppel VL et al (2015) Diet-induced obesity causes metabolic impairment independent of alterations in gut barrier integrity. Mol Nutr Food Res 59:968–978

    Article  CAS  PubMed  Google Scholar 

  26. Koeth RA, Wang Z, Levison BS et al (2013) Intestinal microbiota metabolism of L‑carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med 19:576–585

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kostic AD, Gevers D, Siljander H et al (2015) The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes. Cell Host Microbe 17:260–273

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Le Chatelier E, Nielsen T, Qin J et al (2013) Richness of human gut microbiome correlates with metabolic markers. Nature 500:541–546

    Article  PubMed  Google Scholar 

  29. Lee T, Clavel T, Smirnov K et al (2016) Oral versus intravenous iron replacement therapy distinctly alters the gut microbiota and metabolome in patients with IBD. Gut. doi:10.1136/gutjnl-2015-309940

    Google Scholar 

  30. Lepage P, Hasler R, Spehlmann ME et al (2011) Twin study indicates loss of interaction between microbiota and mucosa of patients with ulcerative colitis. Gastroenterology 141:227–236

    Article  PubMed  Google Scholar 

  31. Ley RE, Backhed F, Turnbaugh P et al (2005) Obesity alters gut microbial ecology. Proc Natl Acad Sci USA 102:11070–11075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Lozupone CA, Stombaugh JI, Gordon JI et al (2012) Diversity, stability and resilience of the human gut microbiota. Nature 489:220–230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Moayyedi P, Surette MG, Kim PT et al (2015) Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized controlled trial. Gastroenterology 149:102–109 (e 106)

    Article  PubMed  Google Scholar 

  34. Muller VM, Zietek T, Rohm F et al (2015) Gut barrier impairment by high-fat diet in mice depends on housing conditions. Mol Nutr Food Res 60(4):897–908. doi:10.1002/mnfr.201500775

    Article  Google Scholar 

  35. Nielsen HB, Almeida M, Juncker AS et al (2014) Identification and assembly of genomes and genetic elements in complex metagenomic samples without using reference genomes. Nat Biotechnol 32:822–828

    Article  CAS  PubMed  Google Scholar 

  36. O’keefe SJ, Li JV, Lahti L et al (2015) Fat, fibre and cancer risk in African Americans and rural Africans. Nat Commun 6:6342

    Article  PubMed  PubMed Central  Google Scholar 

  37. Ocvirk S, Sava IG, Lengfelder I et al (2015) Surface-associated lipoproteins link Enterococcus faecalis virulence to colitogenic activity in IL-10-deficient mice independent of their expression levels. PLOS Pathog 11:e1004911

    Article  PubMed  PubMed Central  Google Scholar 

  38. Qin J, Li R, Raes J et al (2010) A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464:59–65

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Qin J, Li Y, Cai Z et al (2012) A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490:55–60

    Article  CAS  PubMed  Google Scholar 

  40. Reichardt F, Baudry C, Gruber L et al (2013) Properties of myenteric neurones and mucosal functions in the distal colon of diet-induced obese mice. J Physiol (Lond) 591:5125–5139

    Article  CAS  Google Scholar 

  41. Renz H, Von Mutius E, Brandtzaeg P et al (2011) Gene-environment interactions in chronic inflammatory disease. Nat Immunol 12:273–277

    Article  CAS  PubMed  Google Scholar 

  42. Ridaura VK, Faith JJ, Rey FE et al (2013) Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 341:1241214

    Article  PubMed  Google Scholar 

  43. Rossen NG, Fuentes S, Van Der Spek MJ et al (2015) Findings from a randomized controlled trial of fecal transplantation for patients with ulcerative colitis. Gastroenterology 149:110–118 (e 114)

    Article  PubMed  Google Scholar 

  44. Schaubeck M, Clavel T, Calasan J et al (2015) Dysbiotic gut microbiota causes transmissible Crohn’s disease-like ileitis independent of failure in antimicrobial defence. Gut 65(2):225–237. doi:10.1136/gutjnl-2015-309333

    Article  PubMed  PubMed Central  Google Scholar 

  45. Schwiertz A, Taras D, Schafer K et al (2010) Microbiota and SCFA in lean and overweight healthy subjects. Obesity 18:190–195

    Article  PubMed  Google Scholar 

  46. Sokol H, Pigneur B, Watterlot L et al (2008) Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci USA 105:16731–16736

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Steck N, Hoffmann M, Sava IG et al (2011) Enterococcus faecalis metalloprotease compromises epithelial barrier and contributes to intestinal inflammation. Gastroenterology 141:959–971

    Article  CAS  PubMed  Google Scholar 

  48. Suez J, Korem T, Zeevi D et al (2014) Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature 514:181–186

    CAS  PubMed  Google Scholar 

  49. Turnbaugh PJ, Ley RE, Mahowald MA et al (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444:1027–1031

    Article  PubMed  Google Scholar 

  50. Vermeire S, Joossens M, Verbeke K et al (2015) Donor species richness determines Faecal Microbiota transplantation success in inflammatory bowel disease. J Crohns Colitis 10(4):387–394. doi:10.1093/ecco-jcc/jjv203

    Article  PubMed  Google Scholar 

  51. Vrieze A, Van Nood E, Holleman F et al (2012) Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology 143:913–916 (e 917)

    Article  CAS  PubMed  Google Scholar 

  52. Walters WA, Xu Z, Knight R (2014) Meta-analyses of human gut microbes associated with obesity and IBD. FEBS Lett 588:4223–4233

    Article  CAS  PubMed  Google Scholar 

  53. Wang Z, Klipfell E, Bennett BJ et al (2011) Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472:57–63

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Willing BP, Dicksved J, Halfvarson J et al (2010) A pyrosequencing study in twins shows that gastrointestinal microbial profiles vary with inflammatory bowel disease phenotypes. Gastroenterology 139:1844–1854

    Article  PubMed  Google Scholar 

  55. Zeevi D, Korem T, Zmora N et al (2015) Personalized nutrition by prediction of glycemic responses. Cell 163:1079–1094

    Article  CAS  PubMed  Google Scholar 

  56. Zeller G, Tap J, Voigt AY et al (2014) Potential of fecal microbiota for early-stage detection of colorectal cancer. Mol Syst Biol 10:766

    Article  PubMed  PubMed Central  Google Scholar 

  57. Zhang X, Shen D, Fang Z et al (2013) Human gut microbiota changes reveal the progression of glucose intolerance. PLOS ONE 8:e71108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Zhu W, Gregory JC, Org E et al (2016) Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk. Cell 165:111–124

    Article  CAS  PubMed  Google Scholar 

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  1. Lehrstuhl für Ernährung und Immunologie, Technische Universität München, Gregor-Mendel-Str. 2, 85354, Freising, Deutschland

    V. Schüppel &  D. Haller

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  1. V. Schüppel
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  2. D. Haller
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Correspondence to D. Haller.

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V. Schüppel und D. Haller geben an, dass kein Interessenkonflikt besteht.

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

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Schüppel, V., Haller, D. Das Mikrobiom bei chronischen Erkrankungen. Diabetologe 12, 420–427 (2016). https://doi.org/10.1007/s11428-016-0124-3

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