Adipositas - Ursachen, Folgeerkrankungen, Therapie 2019; 13(04): 197-204
DOI: 10.1055/a-0966-9592
Review

Das Mikrobiom bei Adipositas und kardiometabolische Erkrankungen: Die Mischung macht es!

Microbiota in obesity and cardiometabolic diseases: dangerous liaisons or a match made in heaven?
Rima Chakaroun
1   Klinik und Poliklinik für Endokrinologie, Nephrologie und Rheumatologi, Universitätsklinikum Leipzig
2   IFB Integriertes Forschung- und Bildungszentrum Adipositas Erkrankungen, Universitätsklinikum Leipzig
,
Matthias Blüher
1   Klinik und Poliklinik für Endokrinologie, Nephrologie und Rheumatologi, Universitätsklinikum Leipzig
2   IFB Integriertes Forschung- und Bildungszentrum Adipositas Erkrankungen, Universitätsklinikum Leipzig
› Author Affiliations

Zusammenfassung

Das Darmmikrobiom ist ein komplexes Ökosystem, das aus einer Vielzahl von hauptsächlich Bakterien, aber auch Archaeen und Viren besteht. In den letzten Jahren konnte ein starker Zusammenhang zwischen Mikrobiom-Veränderungen und der Entstehung von Erkrankungen, zu denen auch Adipositas und verschiedene Stoffwechselkrankheiten gehören, gefunden werden. Darmbakterien sind an der Synthese essentieller Vitaminen, Extraktionen von Nährstoffen sowie den Abbau von Ballaststoffen beteiligt. Zusätzlich spielt das Mikrobiom eine wichtige Rolle in der Reifung des Immunsystems des Wirts, seiner Darmbarriere, der neuronalen intestinalen Aktivität, und der Produktion und Freisetzung von gastrointestinalen Hormonen. Veränderungen der Zusammensetzung des mikrobiellen Ökosystems im Darm sind mit dem Auftreten von Adipositas, Typ 2 Diabetes, arterieller Hypertonie, nicht alkoholischer Lebererkankung (NAFLD) sowie kardiovaskulären Krankheiten assoziiert.

Vor allem tierexperimentelle Untersuchungen weisen auf einen starken Kausalzusammenhang zwischen dem Mikrobiom und diesen Erkrankungen hin. Hierfür können zusätzlich zu wirtspezifischen oder Umweltfaktoren sowohl Zusammensetzung wie auch die Funktion der Darmbakterien eine chronische systemische Inflammation mitverursachen und unterhalten.

Ein möglichst diverses Mikrobiom kann die metabolische Gesundheit des Wirts positiv beeinflussen und stellt somit einen potentiellen therapeutischen Ansatz bei kardiometabolischen Erkrankungen dar. Beispielsweise werden Stuhltransplantationen zur Therapie unterschiedlicher Erkrankungen wie Clostridium difficile-Infektionen eingesetzt und verbessern auch bei Personen mit Metabolischem Syndrom die Insulinsensitivität. Bevor eine Modulation des Mikrobioms in der Zukunft zur Prävention und Therapie von Adipositas und begleitenden Erkrankungen eingesetzt werden kann, müssen noch weitere klinische Studien die Effektivität und Sicherheit einer gezielten Manipulation der Darmbakterien belegen.

Abstract

The gut microbiota is a complex ecosystem, which mainly consists of bacteria, but also archaea and viruses. During recent years it has been shown that changes in the microbiota are associated with several diseases including obesity and metabolic diseases.

Gut bacteria contribute to the synthesis of essential vitamins, extraction of nutrients and fermentation of indigestible fibres to short chain fatty acids, modulation of bile acids and bile acid signalling. In addition, microbiota play an important role in the maturation of the host´s immune system, the gut barrier function, neuronal intestinal activity and the production of gut hormones. Changes in the microbiota composition are related to the development of obesity, type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), hypertension and cardiovascular diseases. Particularly animal studies have suggested a strong causal relationship between microbiota and the pathophysiology of these diseases. In addition to host specific factors, both the composition and function of the microbiota may contribute to initiating and maintaining chronic systemic inflammation. However, the precise mechanisms linking variations in the gut microbiome with the development of obesity and metabolic diseases in humans are not entirely understood.

A diversified spectrum of gut bacteria may beneficially affect metabolic health of the host and therefore represents a promising target for future therapeutic approaches in the treatment of cardiometabolic diseases.

Emerging applications such as fecal transplants are showing promising results in the resolution of infectious bowel disease and improvement of insulin sensitivity in patients with metabolic syndrome. However, to take advantage of microbiota modulation in the prevention and treatment of obesity and its related diseases, further clinical trials have to prove efficacy and safety of interventions aiming at altering the gut microbiota.



Publication History

Article published online:
02 December 2019

© Georg Thieme Verlag KG
Stuttgart · New York

 
  • Literaturverzeichnis

  • 1 Schlehe JS, Ussar S. Das Mikrobiom: Einfluss auf Adipositas und Diabetes (2016). https://www.aerzteblatt.de/archiv/177992/Das-Mikrobiom-Einfluss-auf-Adipositas-und-Diabetes Stand: 09.01.2019
  • 2 Patterson E, Ryan PM, Cryan JF. et al. Gut microbiota, obesity and diabetes. Postgrad Med J 2016; 92: 286-300
  • 3 Bäckhed F, Manchester JK, Semenkovich CF. et al. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci U S A 2007; 104: 979-984
  • 4 Bäckhed F, Ding H, Wang T. et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A 2004; 101: 15718-15723
  • 5 Turnbaugh PJ, Hamady M, Yatsunenko T. et al. A core gut microbiome in obese and lean twins. Nature 2009; 457: 480-484
  • 6 Ridaura VK, Faith JJ, Rey FE. et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 2013; 341: 1241214
  • 7 Schwiertz A, Taras D, Schäfer K. et al. Microbiota and SCFA in lean and overweight healthy subjects. Obes Silver Spring Md 2010; 18: 190-195
  • 8 Cotillard A, Kennedy SP, Kong LC. et al. Dietary intervention impact on gut microbial gene richness. Nature 2013; 500: 585-588
  • 9 Shin NR, Lee JC, Lee HY. et al. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut 2014; 63: 727-735
  • 10 Amar J, Lange C, Payros G. et al. Blood microbiota dysbiosis is associated with the onset of cardiovascular events in a large general population: the D. E. S. I. R. study. PloS One 2013; 8: e54461
  • 11 Zhang X, Shen D, Fang Z. et al. Human gut microbiota changes reveal the progression of glucose intolerance. PloS One 2013; 8: e71108
  • 12 Qin J, Li Y, Cai Z. et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 2012; 490: 55-60
  • 13 Karlsson FH, Tremaroli V, Nookaew I. et al. Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature 2013; 498: 99-103
  • 14 Cani PD, Bibiloni R, Knauf C. et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 2008; 57: 1470-1481
  • 15 Creely SJ, McTernan PG, Kusminski CM. et al. Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes. Am J Physiol Endocrinol Metab 2007; 292: E740-747
  • 16 Vrieze A, Van Nood E, Holleman F. et al. Transfer of Intestinal Microbiota From Lean Donors Increases Insulin Sensitivity in Individuals With Metabolic Syndrome. Gastroenterology 2012; 143: 913-916 e7
  • 17 Rinella ME. Nonalcoholic fatty liver disease: a systematic review. JAMA 2015; 313: 2263-2273
  • 18 Drenick EJ, Fisler J, Johnson D. Hepatic steatosis after intestinal bypass--prevention and reversal by metronidazole, irrespective of protein-calorie malnutrition. Gastroenterology 1982; 82: 535-548
  • 19 Rabot S, Membrez M, Bruneau A. et al. Germ-free C57BL/6 J mice are resistant to high-fat-diet-induced insulin resistance and have altered cholesterol metabolism. FASEB J Off Publ Fed Am Soc Exp Biol 2010; 24: 4948-4959
  • 20 Chiu CC, Ching YH, Li YP. et al. Nonalcoholic Fatty Liver Disease Is Exacerbated in High-Fat Diet-Fed Gnotobiotic Mice by Colonization with the Gut Microbiota from Patients with Nonalcoholic Steatohepatitis. Nutrients; 2017 9.
  • 21 Henao-Mejia J, Elinav E, Jin C. et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 2012; 482: 179-185
  • 22 Schnabl B, Brenner DA. Interactions Between the Intestinal Microbiome and Liver Diseases. Gastroenterology 2014; 146: 1513-1524
  • 23 Michail S, Lin M, Frey MR. et al. Altered gut microbial energy and metabolism in children with non-alcoholic fatty liver disease. FEMS Microbiol Ecol 2015; 91: 1-9
  • 24 Spencer MD, Hamp TJ, Reid RW. et al. Association between composition of the human gastrointestinal microbiome and development of fatty liver with choline deficiency. Gastroenterology 2011; 140: 976-986
  • 25 Zhu L, Baker SS, Gill C. et al. Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: a connection between endogenous alcohol and NASH. Hepatol Baltim Md 2013; 57: 601-609
  • 26 Mouzaki M, Comelli EM, Arendt BM. et al. Intestinal microbiota in patients with nonalcoholic fatty liver disease. Hepatol Baltim Md 2013; 58: 120-127
  • 27 Mell B, Jala VR, Mathew AV. et al. Evidence for a link between gut microbiota and hypertension in the Dahl rat. Physiol Genomics 2015; 47: 187-197
  • 28 Aoki K, Yamori Y, Ooshima A. et al. Effects of high or low sodium intake in spontaneously hypertensive rats. Jpn Circ J 1972; 36: 539-545
  • 29 Yang T, Santisteban MM, Rodriguez V. et al. Gut dysbiosis is linked to hypertension. Hypertens Dallas Tex 1979 2015; 65: 1331-1340
  • 30 Desvarieux M, Demmer RT, Jacobs DR. et al. Periodontal bacteria and hypertension: the oral infections and vascular disease epidemiology study (INVEST). J Hypertens 2010; 28: 1413-1421
  • 31 Wilck N, Matus MG, Kearney SM. et al. Salt-responsive gut commensal modulates TH17 axis and disease. Nature 2017; 551: 585-589
  • 32 Salt-responsive gut commensal modulates TH17 axis and disease. Nature 2017; 551: 585-589
  • 33 Aihara K, Kajimoto O, Hirata H. et al. Effect of powdered fermented milk with Lactobacillus helveticus on subjects with high-normal blood pressure or mild hypertension. J Am Coll Nutr 2005; 24: 257-265
  • 34 Panel on Dietic Products, Nutrition and Allergies. Scientific Opinion on the substantiation of a health claim related to isoleucyl-prolyl-proline (IPP) and valyl-prolyl-proline (VPP) and maintenance of normal blood pressure pursuant to Article 13(5) of Regulation (EC) No 1924/2006. EFSA Journal 2011; 9: 2380
  • 35 Benjamin EJ, Virani SS, Callaway CW. et al. Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association. Circulation 2018; 137: e67-492
  • 36 Tang WHW, Wang Z, Fan Y. et al. Prognostic value of elevated levels of intestinal microbe-generated metabolite trimethylamine-N-oxide in patients with heart failure: refining the gut hypothesis. J Am Coll Cardiol 2014; 64: 1908-1914
  • 37 Senthong V, Li XS, Hudec T. et al. Plasma Trimethylamine N-Oxide, a Gut Microbe-Generated Phosphatidylcholine Metabolite, Is Associated With Atherosclerotic Burden. J Am Coll Cardiol 2016; 67: 2620-2628
  • 38 Tang WHW, Wang Z, Levison BS. et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med 2013; 368: 1575-1584
  • 39 Fu Q, Zhao M, Wang D. et al. Coronary Plaque Characterization Assessed by Optical Coherence Tomography and Plasma Trimethylamine-N-oxide Levels in Patients With Coronary Artery Disease. Am J Cardiol 2016; 118: 1311-1315
  • 40 Emoto T, Yamashita T, Sasaki N. et al. Analysis of Gut Microbiota in Coronary Artery Disease Patients: a Possible Link between Gut Microbiota and Coronary Artery Disease. J Atheroscler Thromb 2016; 23: 908-921
  • 41 Jie Z, Xia H, Zhong SL. et al. The gut microbiome in atherosclerotic cardiovascular disease. Nat Commun 2017; 8: 845
  • 42 Yamashita T, Emoto T, Sasaki N. et al. Gut Microbiota and Coronary Artery Disease. Int Heart J 2016; 57: 663-671
  • 43 Kootte RS, Levin E, Salojärvi J. et al. Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition. Cell Metab 2017; 26: 611-619 e6
  • 44 Falony G, Joossens M, Vieira-Silva S. et al. Population-level analysis of gut microbiome variation. Science 2016; 352: 560-564
  • 45 Jackson MA, Verdi S, Maxan M-E. et al. Gut microbiota associations with common diseases and prescription medications in a population-based cohort. Nat Commun 2018; 9: 2655
  • 46 Forslund K, Hildebrand F, Nielsen T. et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature 2015; 528: 262-266
  • 47 David LA, Maurice CF, Carmody RN. et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505: 559-563
  • 48 Carmody RN, Gerber GK, Luevano JM. et al. Diet dominates host genotype in shaping the murine gut microbiota. Cell Host Microbe 2015; 17: 72-84
  • 49 Goodrich JK, Waters JL, Poole AC. et al. Human genetics shape the gut microbiome. Cell 2014; 159: 789-799
  • 50 Rothschild D, Weissbrod O, Barkan E. et al. Environment dominates over host genetics in shaping human gut microbiota. Nature 2018; 555: 210-215
  • 51 Deschasaux M, Bouter KE, Prodan A. et al. Depicting the composition of gut microbiota in a population with varied ethnic origins but shared geography. Nat Med 2018; 24: 1526-1531