Diabetes Mellitus’ta Mikrobiyotanın Rolü ve Hedeflenmesi

Year 2021, , 51 - 58, 24.04.2021

Zinnet Şevval Aksoyalp , Cahit Nacitarhan

https://doi.org/10.25048/tudod.711605

Cited By: 2

Abstract

İnsanlarda çoğu kalın bağırsakta olmak üzere 100 trilyonun üzerinde mikrobiyal hücre bulunmaktadır ve bu organizmaların tamamı bağırsak mikrobiyotası olarak adlandırılmıştır. Bağırsak mikrobiyotası gastrointestinal mukoza geçirgenliğinde, bağırsak hormonlarının salımında ve polisakkaritlerin fermantasyonu ve emiliminde önemli rol oynamaktadır. Buna ek olarak bağırsak mikrobiyotası konak
bağışıklık sisteminde, inflamatuvar süreçlerin düzenlenmesinde ve besinlerden enerji üretilmesinde önemli bir role sahiptir. Sağlıklı bağırsak mikrobiyotasında simbiyotik ve patojen bakteriler denge hâlinde bulunmaktadır. Bu dengenin bozulması hem hayvanlarda hem de insanlarda immünolojik ve metabolik bozukluklar ile ilişkilendirilmiştir.
Diabetes mellitus hiperglisemi ile belirgin kronik bir hastalıktır. Son yirmi yılda diabetes mellitus insidansı tüm dünyada hızlı bir şekilde artmış ve önemli bir halk sağlığı sorunu hâline gelmiştir. Genetik ve çevresel faktörlerin yanında bağırsak mikrobiyotası da diabetes mellitus ile ilişkilendirilmiştir. Birçok çalışmada diyabetik hastaların bağırsak mikrobiyotasında orta derecede disbiyozis olduğu gösterilmiştir. Ancak insanlarda diyabet gelişimi ile bağırsak mikrobiyota bileşimi arasındaki ilişki hâlâ belirsizliğini korumaktadır. Bu derlemede bağırsak mikrobiyotası ve diabetes mellitus arasındaki ilişkiye odaklanılarak, diyabet tedavisinde terapötik olarak bağırsak mikrobiyotasının düzenlenmesinin sonuçları tartışılmıştır.

Keywords

Mikrobiyota, diyabetes mellitus, inflamasyon, probiyotikler, prebiyotikler

The Role and Targeting of Microbiota in Diabetes Mellitus

Abstract

There are over 100 trillion microbial cells in the human, mostly in the large intestine, and all of these organisms are gut microbiota. The gut microbiota plays an important role in gastrointestinal mucosal permeability, the secretion of intestinal hormone and fermentation and absorption of dietary polysaccharides. In addition, gut microbiota play an important role in the host’s immune system, regulation
of inflammatory processes and energy production from foods. Symbiotic bacteria and pathogenic bacteria are in equilibrium in the gut microbiota of healthy organisms. The imbalance of gut microbiota has been associated with increased immunological and metabolic
disorders in both animals and humans.
Diabetes mellitus is a chronic disease characterized by hyperglycemia. The incidence of diabetes mellitus has increased rapidly throughout the world in the last twenty-years and has become an important public health problem. Besides genetic and environmental factors, diabetes mellitus has also been associated with gut microbiota. Many studies have shown that diabetic patients have moderate dysbiosis in gut microbiota. However, the relationship between diabetes development and gut microbiota composition remains unclear in humans. In this review, we aimed to focus on the relationship between gut microbiota and diabetes mellitus, and to discuss the results of modulation gut microbiota therapeutically in the treatment of diabetes mellitus.

Keywords

Microbiota, Diabetes mellitus, nflammation, Probiotics, Prebiotics, Probiotics, Prebiotics

References

• 1. Saeedi P, Petersohn I, Salpea P, Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9(th) edition. Diabetes Res Clin Pract. 2019;157:107843.
• 2. Burcelin R, Serino M, Chabo C, Blasco-Baque V, Amar J. Gut microbiota and diabetes: From pathogenesis to therapeutic perspective. Acta Diabetol. 2011;48:257-273.
• 3. Thursby E, Juge N. Introduction to the human gut microbiota. Biochem J. 2017;474:1823-1836.
• 4. Rodriguez JM, Murphy K, Stanton C, Ross R P, Kober OI, Juge N, Avershina E, Rudi K, Narbad A, Jenmalm MC, Marchesi JR, Collado M C. The composition of the gut microbiota throughout life, with an emphasis on early life. Microb Ecol Health Dis. 2015;26:26050.
• 5. Aagaard K, Ma J, Antony K M, Ganu R, Petrosino J, Versalovic J. The placenta harbors a unique microbiome. Sci Transl Med. 2014;6:237ra65.
• 6. Clarke G, Stilling RM, Kennedy PJ, Stanton C, Cryan JF, Dinan TG. Minireview: Gut microbiota: The neglected endocrine organ. Mol Endocrinol. 2014;28:1221-1238.
• 7. Marchesi JR, Adams DH, Fava F, Hermes GD, Hirschfield G M, Hold G, Quraishi MN, Kinross J, Smidt H, Tuohy KM, Thomas LV, Zoetendal EG, Hart A. The gut microbiota and host health: A new clinical frontier. Gut. 2016;65:330-339.
• 8. Gulden E, Wong F S, Wen L. The gut microbiota and Type 1 Diabetes. Clin Immunol. 2015;159:143-53.
• 9. Kachapati K, Adams D, Bednar K, Ridgway WM. The nonobese diabetic (NOD) mouse as a model of human type 1 diabetes. Methods Mol Biol. 2012;933:3-16.
• 10. Pozzilli P, Signore A, Williams AJ, Beales PE. NOD mouse colonies around the world--recent facts and figures. Immunol Today. 1993;14:193-196.
• 11. Wen L, Ley RE, Volchkov PY, Stranges PB, Avanesyan L, Stonebraker AC, Hu C, Wong FS, Szot GL, Bluestone JA, Gordon JI, Chervonsky AV. Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature. 2008;455:1109-1113.
• 12. Brugman S, Klatter FA, Visser JT, Wildeboer-Veloo AC, Harmsen HJ, Rozing J, Bos NA. Antibiotic treatment partially protects against type 1 diabetes in the Bio-Breeding diabetesprone rat. Is the gut flora involved in the development of type 1 diabetes? Diabetologia. 2006;49:2105-2108.
• 13. Roesch LF, Lorca G L, Casella G, Giongo A, Naranjo A, Pionzio AM, Li N, Mai V, Wasserfall CH, Schatz D, Atkinson MA, Neu J, Triplett EW. Culture-independent identification of gut bacteria correlated with the onset of diabetes in a rat model. ISME J. 2009;3:536-548.
• 14. Li WZ, Stirling K, Yang JJ, Zhang L. Gut microbiota and diabetes: From correlation to causality and mechanism. World J Diabetes. 2020;11:293-308.
• 15. Cardwell CR, Stene LC, Joner G, Cinek O, Svensson J, Goldacre MJ, Parslow RC, Pozzilli P, Brigis G, Stoyanov D, Urbonaite B, Sipetic S, Schober E, Ionescu-Tirgoviste C, Devoti G, de Beaufort CE, Buschard K, Patterson CC. Caesarean section is associated with an increased risk of childhood-onset type 1 diabetes mellitus: A meta-analysis of observational studies. Diabetologia. 2008;51:726-735.
• 16. Murri M, Leiva I, Gomez-Zumaquero JM, Tinahones FJ, Cardona F, Soriguer F, Queipo-Ortuno MI. Gut microbiota in children with type 1 diabetes differs from that in healthy children: A case-control study. BMC Med. 2013;11:46.
• 17. Brown CT, Davis-Richardson AG, Giongo A, Gano KA, Crabb DB, Mukherjee N, Casella G, Drew JC, Ilonen J, Knip M, Hyoty H, Veijola R, Simell T, Simell O, Neu J, Wasserfall CH, Schatz D, Atkinson MA, Triplett EW. Gut microbiome metagenomics analysis suggests a functional model for the development of autoimmunity for type 1 diabetes. PLoS One. 2011;6:e25792.
• 18. Kim MH, Kang SG, Park JH, Yanagisawa M, Kim CH. Shortchain fatty acids activate GPR41 and GPR43 on intestinal epithelial cells to promote inflammatory responses in mice. Gastroenterology. 2013;145:396-406 e1-10.
• 19. Kimura I, Ozawa K, Inoue D, Imamura T, Kimura K, Maeda T, Terasawa K, Kashihara D, Hirano K, Tani T, Takahashi T, Miyauchi S, Shioi G, Inoue H, Tsujimoto G. The gut microbiota suppresses insulin-mediated fat accumulation via the shortchain fatty acid receptor GPR43. Nat Commun. 2013;4:1829.
• 20. Kasubuchi M, Hasegawa S, Hiramatsu T, Ichimura A, Kimura I. Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation. Nutrients. 2015;7:2839-2849.
• 21. Cani PD Delzenne NM. The role of the gut microbiota in energy metabolism and metabolic disease. Curr Pharm Des. 2009;15:1546-1558.
• 22. Louis P, Flint HJ. Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine. FEMS Microbiol Lett. 2009;294:1-8.
• 23. Giongo A, Gano KA, Crabb DB, Mukherjee N, Novelo LL, Casella G, Drew JC, Ilonen J, Knip M, Hyoty H, Veijola R, Simell T, Simell O, Neu J, Wasserfall CH, Schatz D, Atkinson M A, Triplett EW. Toward defining the autoimmune microbiome for type 1 diabetes. ISME J. 2011;5:82-91.
• 24. Kostic AD, Gevers D, Siljander H, Vatanen T, Hyotylainen T, Hamalainen AM, Peet A, Tillmann V, Poho P, Mattila I, Lahdesmaki H, Franzosa EA, Vaarala O, de Goffau M, Harmsen H, Ilonen J, Virtanen SM, Clish CB, Oresic M, Huttenhower C, Knip M, Xavier RJ. The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes. Cell Host Microbe. 2015;17:260-273.
• 25. Lavasani S, Dzhambazov B, Nouri M, Fak F, Buske S, Molin G, Thorlacius H, Alenfall J, Jeppsson B, Westrom B. A novel probiotic mixture exerts a therapeutic effect on experimental autoimmune encephalomyelitis mediated by IL-10 producing regulatory T cells. PLoS One. 2010;5:e9009.
• 26. Valladares R, Sankar D, Li N, Williams E, Lai KK, Abdelgeliel AS, Gonzalez CF, Wasserfall CH, Larkin J, Schatz D, Atkinson MA, Triplett EW, Neu J, Lorca GL. Lactobacillus johnsonii N6.2 mitigates the development of type 1 diabetes in BB-DP rats. PLoS One. 2010;5:e10507.
• 27. Higuchi T, Hayashi H, Abe K. Exchange of glutamate and gamma-aminobutyrate in a Lactobacillus strain. J Bacteriol. 1997;179:3362-3364.
• 28. Tian J, Dang H, Chen Z, Guan A, Jin Y, Atkinson MA, Kaufman DL. Gamma-Aminobutyric acid regulates both the survival and replication of human beta-cells. Diabetes. 2013;62:3760-3765.
• 29. Jin Z, Mendu SK, Birnir B. GABA is an effective immunomodulatory molecule. Amino Acids. 2013;45:87-94.
• 30. Marques TM, Wall R, O’Sullivan O, Fitzgerald GF, Shanahan F, Quigley EM, Cotter PD, Cryan JF, Dinan TG, Ross RP, Stanton C. Dietary trans-10, cis-12-conjugated linoleic acid alters fatty acid metabolism and microbiota composition in mice. Br J Nutr. 2015;113:728-738.
• 31. Marques TM, Patterson E, Wall R, O’Sullivan O, Fitzgerald GF, Cotter PD, Dinan TG, Cryan JF, Ross RP, Stanton C. Influence of GABA and GABA-producing Lactobacillus brevis DPC 6108 on the development of diabetes in a streptozotocin rat model. Benef Microbes. 2016;7:409-420.
• 32. Duan F, Curtis KL, March JC. Secretion of insulinotropic proteins by commensal bacteria: rewiring the gut to treat diabetes. Appl Environ Microbiol. 2008;74:7437-7438.
• 33. Duan FF, Liu JH, March JC. Engineered commensal bacteria reprogram intestinal cells into glucose-responsive insulinsecreting cells for the treatment of diabetes. Diabetes. 2015;64:1794-1803.
• 34. Pussinen PJ, Havulinna AS, Lehto M, Sundvall J, Salomaa V. Endotoxemia is associated with an increased risk of incident diabetes. Diabetes Care. 2011;34:392-397.
• 35. Serino M, Luche E, Gres S, Baylac A, Berge M, Cenac C, Waget A, Klopp P, Iacovoni J, Klopp C, Mariette J, Bouchez O, Lluch J, Ouarne F, Monsan P, Valet P, Roques C, Amar J, Bouloumie A, Theodorou V, Burcelin R. Metabolic adaptation to a highfat diet is associated with a change in the gut microbiota. Gut. 2012;61:543-553.
• 36. Amar J, Serino M, Lange C, Chabo C, Iacovoni J, Mondot S, Lepage P, Klopp C, Mariette J, Bouchez O, Perez L, Courtney M, Marre M, Klopp P, Lantieri O, Dore J, Charles M, Balkau B, Burcelin R. Involvement of tissue bacteria in the onset of diabetes in humans: Evidence for a concept. Diabetologia. 2011;54:3055-3061.
• 37. Tilg H, Moschen AR. Microbiota and diabetes: An evolving relationship. Gut. 2014;63:1513-1521.
• 38. Qin J, Li Y, Cai Z, Li S, Zhu J, Zhang F, Liang S, Zhang W, Guan Y, Shen D, Peng Y, Zhang D, Jie Z, Wu W, Qin Y, Xue W, Li J, Han L, Lu D, Wu P, Dai Y, Sun X, Li Z, A metagenomewide association study of gut microbiota in type 2 diabetes. Nature. 2012;490:55-60.
• 39. Karlsson CL, Onnerfalt J, Xu J, Molin G, Ahrne S, Thorngren- Jerneck K. The microbiota of the gut in preschool children with normal and excessive body weight. Obesity. 2012;20:2257- 2261.
• 40. Zhang X, Shen D, Fang Z, Jie Z, Qiu X, Zhang C, Chen Y, Ji L. Human gut microbiota changes reveal the progression of glucose intolerance. PLoS One. 2013;8:e71108.
• 41. 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;63:727-735.
• 42. Forslund K, Hildebrand F, Nielsen T, Falony G, Le Chatelier E, Sunagawa S, Prifti E, Vieira-Silva S, Gudmundsdottir V, Pedersen HK, Arumugam M, Kristiansen K, Voigt AY, Vestergaard H, Hercog R, Costea PI, Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature. 2015;528:262-266.
• 43. Gurung M, Li Z, You H, Rodrigues R, Jump DB, Morgun A, Shulzhenko N. Role of gut microbiota in type 2 diabetes pathophysiology. EBioMedicine. 2020;51:102590.
• 44. 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, Nieuwdorp M. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012;143:913-6 e7.
• 45. Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C, Bindels LB, Guiot Y, Derrien M, Muccioli GG, Delzenne NM, de Vos WM, Cani PD. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci USA. 2013;110:9066-9071.
• 46. Hansen KB, Rosenkilde MM, Knop FK, Wellner N, Diep TA, Rehfeld JF, Andersen UB, Holst JJ, Hansen HS. 2-Oleoyl glycerol is a GPR119 agonist and signals GLP-1 release in humans. J Clin Endocrinol Metab. 2011;96:E1409-417.
• 47. Taneera J, Jin Z, Jin Y, Muhammed SJ, Zhang E, Lang S, Salehi A, Korsgren O, Renstrom E, Groop L, Birnir B. Gamma- Aminobutyric acid (GABA) signalling in human pancreatic islets is altered in type 2 diabetes. Diabetologia. 2012;55:1985- 1994.
• 48. Tian J, Dang HN, Yong J, Chui WS, Dizon MP, Yaw CK, Kaufman DL. Oral treatment with gamma-aminobutyric acid improves glucose tolerance and insulin sensitivity by inhibiting inflammation in high fat diet-fed mice. PLoS One. 2011;6:e25338.
• 49. Lee H, Ko G. Effect of metformin on metabolic improvement and gut microbiota. Appl Environ Microbiol. 2014;80:5935- 5943.
• 50. Wang X, Juan QF, He YW, Zhuang L, Fang YY, Wang YH. Multiple effects of probiotics on different types of diabetes: A systematic review and meta-analysis of randomized, placebocontrolled trials. J Pediatr Endocrinol Metab. 2017;30:611- 622.
• 51. Sun J, Buys NJ. Glucose- and glycaemic factor-lowering effects of probiotics on diabetes: A meta-analysis of randomised placebo-controlled trials. Br J Nutr. 2016;115:1167-1177.
• 52. Tao YW, Gu YL, Mao XQ, Zhang L, Pei YF. Effects of probiotics on type II diabetes mellitus: a meta-analysis. J Transl Med. 2020;18:30.
• 53. Yetkin İ, Satış H, Kayahan Satış N. Bağırsak mikrobiyotasının insülin direnci, diabetes mellitus ve obezite ile ilişkisi. Türkiye Diyabet ve Obezite Dergisi. 2017;2:1-8.
• 54. Hur KY, Lee MS. Gut microbiota and metabolic Disorders. Diabetes Metab J. 2015;39:198-203.