Bağırsak Mikrobiyotasının İnsülin Direnci, Diabetes Mellitus ve Obezite ile İlişkisi

Yıl 2018, Cilt: 2 Sayı: 1, 1 - 8, 01.04.2018

İlhan Yetkin Hasan Yetiş Neslihan Kayahan Satış

Öz

Bütün canlılar, insanlar dahil içerisinde ve üzerinde yaşayan tüm mikroorganizmalara (MO) mikrobiyota (MB) denir. İnsan vücudunda
ökaryotik hücrelerin sayısından daha fazla bir trilyon mikroorganizma vardır. Bu mikroorganizmalar vücudun tamamında bulunur,
ancak en çok kalın bağırsakta bulunurlar. Son yıllarda bedenlerimizdeki bu MO’ların bazı hastalıkların patogenezinde rol oynayabileceği
öne sürülmüştür. Bağırsaklardan kaynaklanan hastalıkları enfeksiyon hastalıkları, toksik hastalıklar ve protein kaynaklı hastalıklar
olarak sınıflandırmak mümkündür. Bu derlemenin amacı son yıllarda mikrobiyoloji araştırmaları ışığında MB, obezite, insülin direnci
ve diabetes mellitus arasındaki ilişkiyi gözden geçirmektir. 

Anahtar Kelimeler

Mikrobiyota, Obezite, İnsulin direnci, diabetes mellitus

Relatinship Between Insulin Resistance, Diabetes Mellitus and Obesity of Gut Microbiata

Öz

The whole of all microorganisms (MO) living in and on all living things, in this particular case it is human, this compilation is called
microbiota (MB). There are more than a trillions of microorganisms in the human body which is more than the number of eukaryotic
cells. These microorganisms are found throughout the body, but are located in the large bowel with the most intensely. In recent years it
has been suggested that these MOs in our bodies may play a role in the pathogenesis of some diseases. It is possible to classify diseases
arising from intestine as infections diseases, toxic diseases and protein induced diseases. The aim of this review is to investigate the
relationship between MB, obesity, insulin resistance and diabetes mellitus in the light of the microbiota research in recent years.

Anahtar Kelimeler

Microbiota, Obesity, Insulin resistance, Diabetes mellitus

Kaynakça

• 1. Qin J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010;464:59-65.
• 2. Chan YK, et al. Clinical consequences of diet-induced dysbiosis. Ann Nutr Metab. 2013;63(suppl 2):28-40.
• 3. Resta SC. Effects of probiotics and commensals on intestinal epithelial physiology: Implications for nutrient handling. J Physiol. 2009;587:4169-4174.
• 4. Donohoe DR, et al. The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell Metab. 2011;13: 517-526.
• 5. Hamer HM, et al. Review article: The role of butyrate on colonic function. Alimentary Pharmacology & Therapeutics, 2008;27:104-119.
• 6. Anitha M, et al. Gut microbial products regulate murine gastrointestinal motility via Toll-like receptor 4 signaling. Gastroenterology. 2012;143:1004.
• 7. Husebye E, et al. Intestinal microflora stimulates myoelectric activity of rat small intestine by promoting cyclic initiation and aboral propagation of migrating myoelectric complex. Dig Dis Sci. 1994;39:946-956.
• 8. Husebye E, et al. Influence of microbial species on small intestinal myoelectric activity and transit in germ-free rats. Am J Physiol Gastrointest Liver Physiol. 2001;280:G368-380.
• 9. Oresic M, et al. Gut microbiota affects lens and retinal lipid composition. Experimental Eye Research. 2009;89;604-607.
• 10. Lee YK, Mazmanian SK. Has the microbiota played a critical role in the evolution of the adaptive immune system? Science. 2010;330:1768-1773.
• 11. Satokari R, et al. Bifidobacterium and lactobacillus DNA in the human placenta. Lett Appl Microbiol. 2009;48:8-12.
• 12. Rautava S, et al. Probiotics modulate host-microbe interaction in the placenta and fetal gut: A randomized, double-blind, placebo- controlled trial. Neonatology. 2012;102:178-184.
• 13. Jimenez E, et al. Isolation of commensal bacteria from umbilical cord blood of healthy neonates born by cesarean section. Curr Microbiol. 2005;51:270-274.
• 14. Turroni F, et al. Diversity of Bifidobacteria within the Infant Gut Microbiota. PLoS ONE. 2012;7(5): 36957.
• 15. Makino H, et al. Mother-to-infant transmission of intestinal bifidobacterial strains has an impact on the early development of vaginally delivered infant’s microbiota. PLoS ONE. 2013; 8(11): 78331.
• 16. Munyaka PM, et al. External influence of early childhood establishment of gut microbiota and subsequent health implications. Frontiers in Pediatrics. 2014;2:109.
• 17. Palmer C, et al. Development of the human infant intestinal microbiota. PLoS Biol. 2007;5(7): 177.
• 18. Faith JJ, et al. The long-term stability of the human gut microbiota. Science. 2013;341(6141):1237439.
• 19. Yatsunenko T, et al. Human gut microbiome viewed across age and geography. Nature, 2012;486(7402): 222-227.
• 20. Kurokawa K, et al. Comparative metagenomics revealed commonly enriched gene sets in human Gut microbiomes. DNA Research. 2007;14:169-181.
• 21. Walker AW, et al. Dominant and diet-responsive groups ofbacteria within the human colonic microbiota. ISME J. 2011;5(2):220-230.
• 22. Ze X, et al. Ruminococcus bromii is a keystone species for the degradation of resistant starch in the human colon. ISME J. 2012;6(8):1535-1543.
• 23. Parkes GC, et al. Gastrointestinal microbiota in irritable bowel syndrome: Their role in its pathogenesis and treatment. Am J Gastroenterol. 2008;103:1557-1567.
• 24. Nell S, et al. The impact of the microbiota on the pathogenesis of IBD: Lessons from mouse infection models. Nat Rev Microbiol. 2010;8:564-577.
• 25. Abu-Shanab A, Quigley EM. The role of the gut microbiota in nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol. 2010;7:691-701.
• 26. Turnbaugh PJ, et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444:1027-1031.
• 27. Cani PD, et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat dietinduced obesity and diabetes in mice. Diabetes. 2008;57:1470-1481.
• 28. Lin HV, et al. Butyrate and propionate protect against dietinduced obesity and regulate gut hormones via free faty acid receptor 3- independent mechanisms nature, 2011. PLoS ONE. 7(4), e35240, 2012; Nutr. Res. Rev. 2010;23:366–384.
• 29. Holmes E, et al. Gut microbiota composition and activity in relation to host metabolic phenotype and disease risk. Cell Metab. 2012;16(5): 559-564.
• 30. den Besten G, et al. Gut-derived short-chain fatty acids are vividly assimilated into host carbohydrates and lipids. American Journal of Physiology - Gastrointestinal and Liver Physiology. 2013;305(12):G900-G910.
• 31. Perry RJ, et al. Acetate mediates a microbiome–brain–β-cell axis to promote metabolic syndrome. Nature, 2016;534(7606):213- 217.
• 32. Carvalho BM, Saad MJ. Influence of gut microbiota on subclinical inflammation and insulin resistance. Mediators Inflamm. 2013;2013:986734.
• 33. Lee JY, Hwang DH. The modulation of inflammatory gene expression by lipids: Mediation through toll-like receptors. Mol Cells 2006;21:174-185.
• 34. Hotamisligil GS, et al. Adipose expression of tumor necrosis factor-α: Direct role in obesity-linked insulin resistance. Science. 1993;259:87–91.
• 35. Monroy A, et al. Impaired regulation of the TNF-α converting enzyme/tissue inhibitor of metalloproteinase 3 proteolytic system in skeletal muscle of obese type 2 diabetic patients: A new mechanism of insulin resistance in humans. Diabetologia. 2009;52:2169–2181.
• 36. Kern PA, et al. Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab. 2001;280:E745- 751.
• 37. Carvalho-Filho MA, et al. S-nitrosation of the insulin receptor, insulin receptor substrate 1, and protein kinase B/Akt: A novel mechanism of insulin resistance. Diabetes. 2005;54: 959–967.
• 38. Cani PD, et al. Metabolic endotoxemia initiates obesity and insülin resistance. Diabetes. 2007;56: 1761-772.
• 39. Hathaway LJ, Kraehenbuhl JP. The role of M cells in mucosal immunity. Cell Mol Life Sci. 2000;57:323-332.
• 40. Hornef MW, et al. Toll-like receptor 4 resides in the golgi apparatus and colocalizes with internalized lipopolysaccharide in intestinal epithelial cells. J Exp Med. 2002;195: 559–570.
• 41. Erridge C, et al. A high-fat meal induces low-grade endotoxemia: Evidence of a novel mechanism of postprandial inflammation. Am J Clin Nutr. 2007;86:1286–1292.
• 42. Ghoshal S, et al. Chylomicrons promote intestinal absorption of lipopolysaccharides. J Lipid Res. 2009;50:90–97.
• 43. Brun P, et al. Increasedintestinal permeability in obese mice: New evidence in the pathogenesis of nonalcoholicsteatohepatitis. Am J Physiol Gastrointest Liver Physiol. 2007;292:518– 525.
• 44. Andrea M, et al. The role of gut microbiota on insulin resistance. Nutrients. 2013;5:829-851.
• 45. Prawitt J, et al. Glucose-lowering effects of intestinal bile acid sequestration through enhancement of splanchnic glucose utilization. Trends Endocrinol Metab. 2014;25 Suppl 5:235– 244.
• 46. Guinane CM, et al. Microbial composition of human appendices from patients following appendectomy. MBio. 2013;15: 4(1).
• 47. Moreno-Indias I, et al. Insulin resistance is associated with specific gut microbiota in appendix samples from morbidly obese patients. Am J Transl Res. 2016;8(12):5672-5684.
• 48. 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.
• 49. Turnbaugh PJ, et al. A core gut microbiome in obese and lean twins. Nature. 2009; 457: 480–484.
• 50. Chatelier E, et al. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013; 500: 541–546.
• 51. Cotillard A. Dietaryintervention impact on gut microbial gene richness. Nature. 2013; 500: 585–588.
• 52. Lozupone CA, et al. Diversity, stability and resilience of the human gut microbiota. Nature. 2012;489(7415):220-230.
• 53. Backhed F, et al. The gut microbiota as an environmentalfactor that regulates fat storage. PNAS. 2004;101:15718–15723.
• 54. Qin J, et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature. 2012; 490: 55–60.
• 55. Karlsson FH, et al. Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature. 2013;498:99–103.
• 56. Ley RE, et al. Microbial ecology: Human gut microbes associated with obesity. Nature. 2006; 444:1022–1023.
• 57. Larsen N, et al. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS ONE. 2010;5: e9085.
• 58. Shin NR, 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.
• 59. Everard A, et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. PNAS. 2013;110: 9066–9071.
• 60. Allin KH, et al. Mechanisms in endocrinology: Gut microbiota in patients with type 2 diabetes mellitus. Eur J Endocrinol. 2015;172(4):R167-177.
• 61. Suez J, et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014; 514: 181–186.
• 62. Clarke SF, et al. Exercise and associated dietary extremes impact on gut microbial diversity. Gut. 2014; 63: 1913–1920.
• 63. Biedermann L, et al. Smoking cessation alters intestinal microbiota: insights from quantitative investigations on human fecal samples using FISH. Inflammatory Bowel Diseases. 2014;20:1496–1501.
• 64. Leclercq S, et al. Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity. PNAS. 2014;111: E4485–E4493.
• 65. Turnbaugh PJ, et al. Organismal, genetic, and transcriptional variation in the deeply sequenced gut microbiomes of identical twins. Proc Natl Acad Sci U.S.A. 2010;107:7503–7508.
• 66. Zhang H, et al. Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci U.S.A. 2009;106:2365–2370.
• 67. Armougom F, et al. Monitoring bacterial community of human gut microbiota reveals an increase in Lactobacillus in obese patients and Methanogens in anorexic patients. PLoS One. 2009;4:e7125.
• 68. Wu X, et al. Molecular characterisation of the faecal microbiota in patients with type II diabetes.Curr Microbiol. 2010;61: 69– 78.
• 69. Lee H, Ko G. Effect of metformin on metabolic improvement and gut microbiota. Appl Environ Microbiol. 2014;80:5935– 5943.
• 70. Brahe LK, et al. Specific gut microbiota features and metabolic markers in postmenopausal women with obesity. Nutr Diabetes. 2015;5:e159.
• 71. Bäckhed F, et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci USA. 2004; 101:15718– 15723.
• 72. Bäckhed F, et al. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci USA. 2007;104: 979– 984.
• 73. Million M, et al. Obesity-associated gut microbiota is enriched in Lactobacillus reuteri and depleted in Bifidobacterium animalis and Methanobrevibacter smithii. Int J Obes. 2012;36:817–825.
• 74. Drissi F, et al. Comparative genomics analysis of Lactobacillus species associated with weight gain or weight protection. Nutr Diabetes. 2014;4:e109.
• 75. Kalliomäki M, et al. Early differences in fecal microbiota composition in children may predict overweight. Am J Clin Nutr. 2008;87:534–538.
• 76. Bailey LC, et al. Association of antibiotics in infancy with early childhood obesity. JAMA Pediatrics. 2014;168:1063–1069.
• 77. Membrez M, et al. Gut microbiota modulation with norfloxacin and ampicillin enhances glucose tolerance in mice. FASEB Journal. 2008; 22:2416–2426.
• 78. Carvalho BM, et al. Modulation of gut microbiota by antibiotics improves insulin signalling in high-fat fed mice. Diabetologia. 2012;55: 2823–2834.
• 79. Ley RE, et al. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell. 2006; 124: 837–848.
• 80. Park JE, et al. Lactobacillus plantarum LG42 isolated from gajami sik-hae decreases body and fat pad weights in dietinduced obese mice. J App Microbiol. 2014;116:145-156.
• 81. Miyoshi M, et al. Anti-obesity effect of Lactobacillus gasseri SBT2055 accompanied by inhibition of proinflammatory gene expression in the visceral adipose tissue in dietinduced obese mice. Eur J Nutr. 2014;53:599-606.
• 82. Park DY, et al. Supplementation of Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032 in diet-induced obese mice is associated with gut microbial changes and reduction in obesity. PLoS One. 2013;8:e59470.
• 83. Kadooka Y, et al. Regulation of abdominal adiposity by probiotics (Lactobacillus gasseri SBT2055) in adults with obese tendencies in a randomized controlled trial. Eur J Clin Nutr. 2010;64:636-643.
• 84. Kadooka Y, et al. Effect of Lactobacillus gasseri SBT2055 in fermented milk on abdominal adiposity in adults in a randomised controlled trial. Br J Nutr. 2013;110:1696-1703.
• 85. Ogawa A, et al. Lactobacillus gasseri SBT2055 reduces postprandial and fasting serum non-esterified fatty acid levels in Japanese hypertriacylglycerolemic subjects. Lipid Health Dis. 2014;13:36.