The Role of Intestinal Microbiota in Obesity, Inculin resistance and Diabetes

Year 2017, - Mikrobiyota, 68 - 80, 15.11.2017

Fatih Kuzu

Abstract

Diabetes mellitus and obesity are very common health problems. These metabolic diseases have become a global health problem all over the world and have begun to increase rapidly in all ages, starting with childhood and adolescence in many countries. Until today, the desired success has not been achieved with calorie restriction and medical treatment. Recent studies have provided new targets for understanding the biochemical pathways involved in the development of obesity and diabetes. Recent evidence has also shown that intestinal microbiota plays a potential new role in the pathogenesis of metabolic disorders such as obesity, insulin resistance, type 1 diabetes (T1D) and type 2 diabetes (T2D). Specifi c metabolites such as short chain fatty acids (SCFA), bile acid and bioactive lipids of the intestinal microbiota contribute to the regulation of incretin hormone secretion by activating receptors that are expressed on enteroendocrine L cells. These incretin hormone peptides affect a wide spectrum of organs and tissues such as the gastrointestinal tract, brain, fat tissue and liver. Understanding the role of intestinal microbiota in the pathophysiology of metabolic diseases has led to new therapeutic options such as prebiotics, probiotics and fecal transplantation. Intestinal microbiata modifi cation may be a potential therapeutic strategy for the prevention of obesity and diabetes or the reversal of the process.

Keywords

type 1 diabetes (T1D), type 2 diabetes (T2D), obesity, microbiota, insulin resistance

Bağırsak Mikrobiyotasının Obezite, İnsülin Direnci ve Diyabetteki Rolü

Abstract

Diyabetes mellitus ve obezite çok sık görülen bir sağlık sorunudur. Bu metabolik hastalıklar tüm dünyada küresel bir sağlık sorunu haline gelmiş ve pek çok ülkede çocukluk ve adölesan çağdan başlayarak tüm yaş dönemlerinde hızla artmaya başlamıştır. Bugüne kadar kalori kısıtlaması ve medikal tedavi ile istenilen başarıya ulaşılamamıştır. Son çalışmalar obezitenin ve diyabetin gelişimi ile ilgili biyokimyasal yolları anlamaya yönelik yeni hedefl er sağlamıştır. Yakın geçmişte biriken kanıtlar da bağırsak mikrobiyotasının obezite, insülin direnci, tip 1 diyabet (T1D) ve tip 2 diyabet (T2D) gibi metabolik bozuklukların patogenezinde potansiyel yeni bir katkıda rol oynadığını ortaya koymuştur. Bağırsak mikrobiyotasına ait kısa zincirli yağ asitleri (KZYA), safra asiti ve biyoaktif lipidler gibi spesifi k metabolitler, enteroendokrin L hücrelerinde eksprese olan reseptörlerini aktive ederek inkretin hormon sekresyonunun düzenlenmesine katkıda bulunur. Bu inkretin hormon peptidleri gastrointestinal sistem, beyin, yağ dokusu ve karaciğer gibi geniş bir organ ve doku yelpazesini etkilemektedir. Bağırsak mikrobiyotasının metabolik hastalıkların patofizyolojisindeki rolünün anlaşılması ile prebiyotikler, probiyotikler ve fekal transplantasyon gibi yeni tedavi seçenekleri gündeme gelmiştir. Bağırsak mikrobiyota modifi kasyonu, obezitenin ve diyabetin önlenmesi veya sürecin tersine çevrilmesi için potansiyel bir terapötik strateji olabilir.

Keywords

tip 1 diyabet (T1D), tip 2 diyabet (T2D), insülin direnci, obezite, mikrobiyota

References

• 1. Everard A, Cani PD. Diabetes, obesity and gut microbiota. Best practice & research Clinical gastroenterology 2013;27(1):73-83.
• 2. McLaughlin T, Abbasi F, Carantoni M, Schaaf P, Reaven G. Differences in insulin resistance do not predict weight loss in response to hypocaloric diets in healthy obese women. J Clin Endocrinol Metab 1999;84:578–81.
• 3. Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006;444:840–6.
• 4. McLaughlin TL, Reaven GM. Beyond type 2 diabetes: the need for a clinically useful way to identify insulin resistance. Am J Med 2003;114:501–2.
• 5. Makino H, Kushiro A, Ishikawa E, Kubota H, Gawad A, Sakai T, Oishi K, Martin R, Ben-Amor K, Knol J, Tanaka R. Mother-to-infant transmission of intestinal bifi dobacterial strains has an impact on the early development of vaginally delivered infant’s microbiota. PLoS One. 2013;8:e78331.
• 6. Munyaka PM, Khafi pour E, Ghia JE. External infl uence of early childhood establishment of gut microbiota and subsequent health implications. Front Pediatr. 2014;2:109.
• 7. Power SE, O’Toole PW, Stanton C, Ross RP, Fitzgerald GF. Intestinalmicrobiota, diet and health. Br J Nutr 2014;111:387–402.
• 8. Mika A, Van Treuren W, González A, Herrera JJ, Knight R, FleshnerM. Exercise is more effective at altering gut microbial composition andproducing stable changes in lean mass in juvenile versus adult male F344rats. PLoS One 2015;10:e0125889.
• 9. Prakash S, Rodes L, Coussa-Charley M, Tomaro-Duchesneau C. Gutmicrobiota: next frontier in understanding human health and developmentof biotherapeutics. Biologics 2011;5:71–86.
• 10. Blandino G, et al. Impact of gut microbiota on diabetes mellitus. Diabetes & metabolism 2016;42(5):303-315.
• 11. Sekirov I, Russell SL, Antunes LC, Finlay BB. Gut microbiota in health and disease. Physiol Rev. 2010;90(3):859-904.
• 12. Bianconi E, Piovesan A, Facchin F, Beraudi A, Casadei R, Frabetti F, et al. An estimation of the number of cells in the human body. Ann Hum Biol. 2013;40(6):463-71.
• 13. Baothman OA, et al. The role of gut microbiota in the development of obesity and diabetes. Lipids in health and disease 2016 ;15(1): 108.
• 14. Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, Sogin ML, Jones WJ, Roe BA, Affourtit JP, et al. A core gut microbiome in obese and lean twins. Nature 2009;457:480–484
• 15. Brown AJ, Goldsworthy SM, Barnes AA, et al. The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem 2003;278:11312-9.
• 16. He C, Shan Y, Song W. Targeting gut microbiota as a possible therapy for diabetes. Nutrition Research 2015;35(5):361-367.
• 17. Ang Z, Ding JL. GPR41 and GPR43 in Obesity and Infl ammation– Protective or Causative?.Frontiers in immunology 2016;7
• 18. Yang JY, Kweon MN. The gut microbiota: a key regulator of metabolic diseases. BMB reports 2016 ;49(10): 536.
• 19. Sayin SI, Wahlstrom A, Felin J et al. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab 2013;17:225-235
• 20. Swann JR, Want EJ, Geier FM et al. Systemic gut microbial modulation of bile acid metabolism in host tissue compartments. Proc Natl Acad Sci U S A 2011;108 Suppl 1:4523-4530
• 21. Sato H, Genet C, Strehle A et al. Anti-hyperglycemic activity of a TGR5 agonist isolated from Olea europaea. Biochem Biophys Res Commun 2007;362:793-798
• 22. Thomas C, Gioiello A, Noriega L, Strehle A, Oury J, Rizzo G, et al. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab 2009;10(3):167–77.
• 23. Cani, Patrice D., Amandine Everard, and Thibaut Duparc. Gut microbiota, enteroendocrine functions and metabolism. Current opinion in pharmacology 2013;13(6):935-940.
• 24. Han JL, Lin HL. Intestinal microbiota and type 2 diabetes: from mechanism insights to therapeutic perspective. World journal of gastroenterology: WJG 2014;20(47):17737.
• 25. Cani PD, Knauf C, Iglesias MA, Drucker DJ, Delzenne NM, Burcelin R: Improvement of glucose tolerance and hepatic insulin sensitivity by oligofructose requires a functional glucagon-like peptide 1 receptor. Diabetes 2006;55:1484-1490.
• 26. Baggio LL, Daniel JD. Biology of incretins: GLP-1 and GIP. Gastroenterology 2007;132(6):2131-2157.
• 27. Grandt D, et al. Two molecular forms of peptide YY (PYY) are abundant in human blood: characterization of a radioimmunoassay recognizing PYY 1–36 and PYY 3–36. Regulatory peptides 1994 ;51(2):151-159.
• 28. Ley RE, Backhed F, Turnbaugh P, Lozupone CA, Knight RD and Gordon JI. Obesity alters gut microbial ecology. Proc Natl Acad Sci U S A 2005;102:11070-11075
• 29. Ley RE, Turnbaugh PJ, Klein S and Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature 2006;444:1022-1023
• 30. Mai V, McCrary QM, Sinha R, Glei M. Associations between dietary habits and body mass index with gut microbiota composition and fecal water genotoxicity: an observational study in African American and Caucasian American volunteers. Nutr J 2009;8:49.
• 31. Schwiertz A, Taras D, Schafer K et al. Microbiota and SCFA in lean and overweight healthy subjects. Obesity 2010;18:190-195
• 32. Duncan SH, Belenguer A, Holtrop G, Johnstone AM, Flint HJ and Lobley GE. Reduced dietary intake of carbohydrates by obese subjects results in decreased concentrations of butyrate and butyrate-producing bacteria in feces. Appl Environ Microbiol 2007;73:1073-1078
• 33. Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, Fava F, Tuohy KM, Chabo C, Waget A, Delmée E, Cousin B, Sulpice T, Chamontin B, Ferrières J, Tanti JF, Gibson GR, Casteilla L, Delzenne NM, Alessi MC, Burcelin R. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 2007;56:1761-1772
• 34. Zhanguo G, et al. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes 2009:58(7);1509-1517.
• 35. Engels C, et al. The common gut microbe Eubacterium hallii also contributes to intestinal propionate formation. Frontiers in microbiology 2016;7
• 36. Udayappan S et al. Oral treatment with Eubacterium hallii improves insulin sensitivity in db/db mice. npj Biofi lms and Microbiomes 2016;(2):16009.
• 37. Rivière A, Selak M, Lantin D, Leroy F, De Vuyst L. Bifi dobacteria and butyrate-producing colon bacteria: importance and strategies for their stimulation in the human gut. Frontiers in microbiology 2016;7.
• 38. Lin HV, Frassetto A, Kowalik EJ Jr, Nawrocki AR, Lu MM, Kosinski JR, Hubert JA, Szeto D, Yao X, Forrest G et al.: Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLOS ONE 2012, 7:e35240.
• 39. Bruce-Keller AJ, et al. Obese-type gut microbiota induceneurobehavioral changes in the absence of obesity. Biological psychiatry 2015; 77(7):607-615.
• 40. Zhang H, et al. Human gut microbiota in obesity and after gastric bypass. Proceedings of the National Academy of Sciences 2009;106(7):2365-2370.
• 41. Liou AP, et al. Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity.Science translational medicine 2013;5(178):178ra41-178ra41.
• 42. Larsen N, et al. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PloS one 2010 ;5(2): e9085.
• 43. Osto M, et al. Roux-en-Y gastric bypass surgery in rats alters gut microbiota profi le along the intestine. Physiology & behavior 2013;119:92-96.
• 44. Yang JY, et al. Gut commensal Bacteroides acidifaciens prevents obesity and improves insulin sensitivity in mice. Mucosal immunology 2017;10(1):104-116.
• 45. Lê KA, Li Y, Xu X, Yang W, Liu T, Zhao X, et al. Alterations in fecalLactobacillus and Bifi dobacterium species in type 2 diabetic patients inSouthern China population. Front Physiol 2013;3:496.
• 46. Qin, J.,Li,Y.,Cai,Z.,Li,S.,Zhu,J.,Zhang,F.,et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 2012;490:55–60
• 47. Karlsson FH, Tremaroli V, Nookaew I, Bergström G, Behre CJ, Fagerberg B, et al. Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature 2013;498:99–103
• 48. Zhang X et al. Human gut microbiota changes reveal the progression of glucose intolerance. PLoS One. 2013;8(8):e71108.
• 49. Bermudez S, Francisco J, et al. Role of cannabinoid CB 2 receptors in glucose homeostasis in rats. European journal of pharmacology 2007;565(1):207-211.
• 50. Hu C, Wong FS, Wen L. Type 1 diabetes and gut microbiota: Friend or foe?. Pharmacological research 2015;98:9-15.
• 51. Tuomilehto J. The emerging global epidemic of type 1 diabetes. Curr Diab Rep2013;13:795–804.
• 52. Krogvold L, Edwin B, Buanes T, Frisk G, Skog O, Anagandula M, et al. Detec-tion of a low-grade enteroviral infection in the islets of Langerhans of livingpatients newly diagnosed with type 1 diabetes. Diabetes 2014.
• 53. Hansen CH, Krych L, Buschard K, Metzdorff SB, Nellemann C, Hansen LH, et al.A maternal gluten-free diet reduces infl ammation and diabetes incidence inthe offspring of NOD mice. Diabetes 2014;63:2821–32.
• 54. Giongo A, Gano KA, Crabb DB, Mukherjee N, Novelo LL, Casella G, et al.Toward defi ning the autoimmune microbiome for type 1 diabetes. ISME J 2011;5:82–91.
• 55. de Goffau MC, Luopajarvi K, Knip M, Ilonen J, Ruohtula T, Harkonen T, et al.Fecal microbiota composition differs between children with beta-cell autoim-munity and those without. Diabetes 2013;62:1238–44.
• 56. Brugman S, Klatter FA, Visser J, Bos NA, Elias D, Rozing J. Neonatal oraladministration of DiaPep277, combined with hydrolysed casein diet, protectsagainst Type 1 diabetes in BB-DP rats. An experimental study. Diabetologia 2004;47:1331–3.
• 57. Scott FW, Rowsell P, Wang GS, Burghardt K, Kolb H, Flohe S. Oral exposureto diabetes-promoting food or immunomodulators in neonates alters gutcytokines and diabetes. Diabetes 2002;51:73– 8.
• 58. Hansen CH, Krych L, Nielsen DS, Vogensen FK, Hansen LH, SorensenSJ, et al. Early life treatment with vancomycin propagates Akkermansiamuciniphila and reduces diabetes incidence in the NOD mouse. Diabetologia 2012;55:2285–94.
• 59. Calcinaro F, Dionisi S, Marinaro M, Candeloro P, Bonato V, Marzotti S, et al.Oral probiotic administration induces interleukin-10 production and pre-vents spontaneous autoimmune diabetes in the non-obese diabetic mouse.Diabetologia 2005;48:1565–75.
• 60. Robert S, Gysemans C, Takiishi T, Korf H, Spagnuolo I, Sebastiani G, et al. Oraldelivery of glutamic acid decarboxylase (GAD)-65 and IL10 by Lactococcuslactis reverses diabetes in recent-onset NOD mice. Diabetes 2014;63:2876–87.
• 61. Hur KY. Gut Microbiota and Metabolic Disorders. The Journal of Korean Diabetes 2017;18(2):63-70.
• 62. Delzenne NM, Neyrinck AM, Backhed F, Cani PD: Targeting gut microbiota in obesity: effects of prebiotics and probiotics. Nat Rev Endocrinol 2011:;7:639-646.
• 63. Ejtahed HS, et al. Probiotic yogurt improves antioxidant status in type 2 diabetic patients. Nutrition 2012;28(5):539-543.
• 64. Shin NR, Lee JC, Lee HY, Kim MS, Whon TW, Lee MS, Bae JW. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut 2014;63:727-35.
• 65. Shan M, Gentile M, Yeiser JR, Walland AC, Bornstein VU, Chen K, He B, Cassis L, Bigas A, Cols M, Comerma L, Huang B, Blander JM, Xiong H, Mayer L, Berin C, Augenlicht LH, Velcich A, Cerutti A. Mucus enhances gut homeostasis and oral tolerance by delivering immunoregulatory signals. Science 2013;342:447-53.
• 66. van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, Visser CE, Kuijper EJ, Bartelsman JF, Tijssen JG, Speelman P, Dijkgraaf MG, Keller JJ. Duodenal infusion of donor feces for recurrent Clostridium diffi cile. N Engl J Med 2013;368:407-15.
• 67. Vrieze A, Van Nood E, Holleman F, Salojarvi J, Kootte RS, Bartelsman JF, Dallinga-Thie GM, Ackermans MT, Serlie MJ, Oozeer R, Derrien M, Druesne A, Van Hylckama Vlieg JE, Bloks VW, Groen AK, Heilig HG, Zoetendal EG, Stroes ES, de Vos WM, Hoekstra JB, Nieuwdorp M. Transfer of intestinal microbiota from lean donors increases insulin sensiti vity in individuals with metabolic syndrome. Gastroenterology 2012;143:913-6.e7.