Analysis of gut microbiota of obese individuals with type 2 diabetes and healthy individuals

Autoři: Aftab Ahmad aff001;  Wanwei Yang aff002;  Guofang Chen aff002;  Muhammad Shafiq aff001;  Sundus Javed aff001;  Syed Shujaat Ali Zaidi aff001;  Ramla Shahid aff001;  Chao Liu aff002;  Habib Bokhari aff001
Působiště autorů: Department of Biosciences, COMSATS University, Chak Shahzad, Islamabad, Pakistan aff001;  Endocrine and Diabetes Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China aff002
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article


Type 2 diabetes mellitus (T2DM) accounts for 90% of diabetes cases worldwide. The majority of T2DM patients are obese. Dysbiosis in the gut microflora is strongly associated with the pathogenesis of obesity and T2DM; however, the microbiome of obese-T2DM individuals in the Pakistani population remains unexplored. The gut microbiota signature of 60 Pakistani adults was studied using 16S rRNA sequencing targeting V3–V4 hypervariable regions. The sequence analysis revealed that bacteria from Firmicutes were predominant along with those from Clostridia and Negativicutes, whereas bacteria from Verrucomicrobia, Bacteroidetes, Proteobacteria, and Elusimicrobia were less abundant among the obese T2DM patients. These data distinctively vary from those in reports on the Indian population. The difference in gut microbiota could presumably be related to the distinct lifestyle and eastern dietary habits (high carbohydrate and fat intake, low fiber intake) and unregulated antibiotic consumption. This is the first study carried out to understand the gut microbiome and its correlation with individual life style of obese T2DM patients in the Pakistani population.

Klíčová slova:

Clostridium – Gut bacteria – Microbiome – Obesity – Sequence databases – Species diversity


1. World Health Organization. World health statistics 2016: monitoring health for the SDGs, sustainable development goals. WHO Library Cataloguing-in-Publication Data World. 2016.

2. Kahn BB, Flier JS. On diabetes : insulin resistance Obesity and insulin resistance. The Journal of Clinical Investigation. 2000; 10(4):473–481. doi: 10.1172/JCI10842.on

3. Okazaki F, Zang L, Nakayama H, Chen Z, Gao ZJ, Chiba H, et al. Microbiome Alteration in Type 2 Diabetes Mellitus Model of Zebrafish. Scientific Reports. 2019; 29;9(1):87. doi: 10.1038/s41598-018-36442-9 30643152

4. Koopman KE, Booij J, Fliers E, Serlie MJ, la Fleur SE. Diet-induced changes in the lean brain: Hypercaloric high-fat-high-sugar snacking decreases serotonin transporters in the human hypothalamic region. Molecular Metabolism. 2013;2(4):417–422. doi: 10.1016/j.molmet.2013.07.006 24327957

5. Tsukumo DM, Carvalho BM, Carvalho-Filho MA, Saad MJA. Translational research into gut microbiota: new horizons in obesity treatment Pesquisa translacional em microbiota intestinal: novos horizontes no tratamento da obesidade. Arq Bras Endocrinol Metab Arq Bras Endocrinol Metab. 2009;53(2):139–144.

6. Harsch I, Konturek P. The Role of Gut Microbiota in Obesity and Type 2 and Type 1 Diabetes Mellitus: New Insights into “Old” Diseases. Medical Sciences. 2018;6(2):32. doi: 10.3390/medsci6020032 29673211

7. Komaroff AL. The microbiome and risk for obesity and diabetes. JAMA—Journal of the American Medical Association. 2017;317(4):355–356. doi: 10.1001/jama.2016.20099 28006047

8. Larsen N, Vogensen FK, Van Den Berg FWJ, Nielsen DS, Andreasen AS, Pedersen BK, et al. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS ONE. 2010;136(5):1476–1483. doi: 10.1371/journal.pone.0009085 20140211

9. Zhang X, Shen D, Fang Z, Jie Z, Qiu X, Zhang C, et al. Human Gut Microbiota Changes Reveal the Progression of Glucose Intolerance. PLoS ONE. 2013;8(8):e71108. doi: 10.1371/journal.pone.0071108 24013136

10. Naseer M, Bibi F, Alqahtani M, Chaudhary A, Azhar E, Kamal M, et al. Role of Gut Microbiota in Obesity, Type 2 Diabetes and Alzheimer’s Disease. CNS & Neurological Disorders—Drug Targets. 2014; 13(2):305–311. doi: 10.2174/18715273113126660147 24059313

11. Dicksved J, Flöistrup H, Bergström A, Rosenquist M, Pershagen G, Scheynius A, et al. Molecular fingerprinting of the fecal microbiota of children raised according to different lifestyles. Applied and Environmental Microbiology. 2007;73(7):2284–2289. doi: 10.1128/AEM.02223-06 17293501

12. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444(7122):1027. doi: 10.1038/nature05414 17183312

13. Clemente JC, Ursell LK, Parfrey LW, Knight R. The impact of the gut microbiota on human health: An integrative view. Cell. 2012;148(6): 1258–1270. doi: 10.1016/j.cell.2012.01.035 22424233

14. Barengolts E. Gut microbiota, prebiotics, probiotics, and synbiotics in management of obesity and prediabetes: review of randomized controlled trials. Endocrine Practice. 2016;22(10):1224–1234. doi: 10.4158/EP151157.RA 27409822

15. Valdes AM, Walter J, Segal E, Spector TD. Role of the gut microbiota in nutrition and health. BMJ. 2018; 361:2179. doi: 10.1136/bmj.k2179 29899036

16. Shin NR, Whon TW, Bae JW. Proteobacteria: Microbial signature of dysbiosis in gut microbiota. Trends in Biotechnology. 2015; 33(9):496–503. doi: 10.1016/j.tibtech.2015.06.011 26210164

17. Kasai C, Sugimoto K, Moritani I, Tanaka J, Oya Y, Inoue H, et al. Comparison of the gut microbiota composition between obese and non-obese individuals in a Japanese population, as analyzed by terminal restriction fragment length polymorphism and next-generation sequencing. BMC Gastroenterology. 2015; 15(1):100. doi: 10.1186/s12876-015-0330-2 26261039

18. Yasir M, Angelakis E, Bibi F, Azhar EI, Bachar D, Lagier JC, et al. Comparison of the gut microbiota of people in France and Saudi Arabia. Nutrition and Diabetes. 2015; 5(4):e153. doi: 10.1038/nutd.2015.3 25915742

19. Sedighi M, Razavi S, Navab-Moghadam F, Khamseh ME, Alaei-Shahmiri F, Mehrtash A, et al. Comparison of gut microbiota in adult patients with type 2 diabetes and healthy individuals. Microbial Pathogenesis. 2017; 111:362–369. doi: 10.1016/j.micpath.2017.08.038 28912092

20. Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, et al. A core gut microbiome in obese and lean twins. Nature. 2009; 457(7228):480. doi: 10.1038/nature07540 19043404

21. Tilg H, Moschen AR, Kaser A. Obesity and the Microbiota. Gastroenterology. 2009; 136(5):1476–1483. doi: 10.1053/j.gastro.2009.03.030 19327360

22. Verdam FJ, Fuentes S, De Jonge C, Zoetendal EG, Erbil R, Greve JW, et al. Human intestinal microbiota composition is associated with local and systemic inflammation in obesity. Obesity. 2013; 21(12):e607–615. doi: 10.1002/oby.20466 23526699

23. Wang J, Qin J, Li Y, Cai Z, Li S, Zhu J, et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature. 2012; 490(7418):55. doi: 10.1038/nature11450 23023125

24. Brooks AW, Priya S, Blekhman R, Bordenstein SR. Gut microbiota diversity across ethnicities in the United States. PLoS Biology. 2018; 16(12):e200842. doi: 10.1371/journal.pbio.2006842 30513082

25. Gill RK, Kumar A, Malhotra P, Maher D, Singh V, Dudeja PK, et al. Regulation of intestinal serotonin transporter expression via epigenetic mechanisms: Role of HDAC2. American Journal of Physiology—Cell Physiology. 2013; 304(4):c334–341. doi: 10.1152/ajpcell.00361.2012 23195070

26. Won Y-J, Lu VB, Puhl HL, Ikeda SR. -Hydroxybutyrate Modulates N-Type Calcium Channels in Rat Sympathetic Neurons by Acting as an Agonist for the G-Protein-Coupled Receptor FFA3. Journal of Neuroscience. 2013; 33(49):19314–19325. doi: 10.1523/JNEUROSCI.3102-13.2013 24305827

27. Batool M, Ali SB, Jaan A, Khalid K, Ali SA, Kamal K, et al. Initial Sequencing and Characterization of Gastrointestinal and Oral Microbiota in Urban Pakistani Adults Reveals Abnormally High Levels of Potentially Starch Metabolizing Bacteria in the General Population. bioRxiv. 2018; 1:419598. doi: 10.1101/419598

28. Nossa CW, Oberdorf WE, Yang L, Aas JA, Paster BJ, de Santis TZ, et al. Design of 16S rRNA gene primers for 454 pyrosequencing of the human foregut microbiome. World Journal of Gastroenterology. 2010; 16(33):4135. doi: 10.3748/wjg.v16.i33.4135 20806429

29. Mohsin A, Zafar J, Nisar Y Bin, Imran SM, Zaheer K, Khizar B, et al. Frequency of the metabolic syndrome in adult type2 diabetics presenting to Pakistan Institute of Medical Sciences. Journal of the Pakistan Medical Association. 2007; 57(5):235. 17571478

30. Tandon D, Haque MM, Saravanan R, Shaikh S, Sriram P, Dubey AK, et al. A snapshot of gut microbiota of an adult urban population from Western region of India. PLoS ONE. 2018; 13(4):e0195643. doi: 10.1371/journal.pone.0195643 29624599

31. Pushpanathan P, Srikanth P, Seshadri K, Selvarajan S, Pitani R, Kumar T, et al. Gut Microbiota in Type 2 Diabetes Individuals and Correlation with Monocyte Chemoattractant Protein1 and Interferon Gamma from Patients Attending a Tertiary Care Centre in Chennai, India. Indian Journal of Endocrinology and Metabolism. 2016; 20(4):523. doi: 10.4103/2230-8210.183474 27366720

32. Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: Human gut microbes associated with obesity. Nature. 2006; 444(7122):1022. doi: 10.1038/4441022a 17183309

33. Zhang H, DiBaise JK, Zuccolo A, Kudrna D, Braidotti M, Yu Y, et al. Human gut microbiota in obesity and after gastric bypass. Proceedings of the National Academy of Sciences. 2009; 106(7):2365–2370. doi: 10.1073/pnas.0812600106 19164560

34. Peterson J, Garges S, Giovanni M, McInnes P, Wang L, Schloss JA, et al. The NIH Human Microbiome Project. Genome Research. 2009; 19(12):2317–2323. doi: 10.1101/gr.096651.109 19819907

35. Sepp E, Kolk H, Lõivukene K, Mikelsaar M. Higher blood glucose level associated with body mass index and gut microbiota in elderly people. Microbial Ecology in Health & Disease. 2014; 25(1):22857. doi: 10.3402/mehd.v25.22857 24936169

36. Sun L, Yu Z, Ye X, Zou S, Li H, Yu D, et al. A marker of endotoxemia is associated with obesity and related metabolic disorders in apparently healthy Chinese. Diabetes Care. 2010; 33(9):1925–1932. doi: 10.2337/dc10-0340 20530747

37. Erejuwa OO, Sulaiman SA, Ab Wahab MS. Modulation of gut microbiota in the management of metabolic disorders: The prospects and challenges. International Journal of Molecular Sciences. 2014; 15(3):4158–4188. doi: 10.3390/ijms15034158 24608927

38. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, et al. The hormone resistin links obesity to diabetes. Nature. 2001; 409(6818):307. doi: 10.1038/35053000 11201732

39. Wium C, Eggesbø HB, Ueland T, Michelsen AE, Torjesen PA, Aukrust P, et al. Adipose tissue distribution in relation to insulin sensitivity and inflammation in Pakistani and Norwegian subjects with type 2 diabetes. Scandinavian Journal of Clinical and Laboratory Investigation. 2014; 74(8):700–707. doi: 10.3109/00365513.2014.953571 25223599

40. Flint HJ, Scott KP, Duncan SH, Louis P, Forano E. Microbial degradation of complex carbohydrates in the gut. Gut Microbes. 2012; 3(4):289–306. doi: 10.4161/gmic.19897 22572875

41. El Kaoutari A, Armougom F, Gordon JI, Raoult D, Henrissat B. The abundance and variety of carbohydrate-active enzymes in the human gut microbiota. Nature Reviews Microbiology. 2013; 11(7): 497. doi: 10.1038/nrmicro3050 23748339

42. Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, et al. Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nature Medicine. 2013; 19(5):576. doi: 10.1038/nm.3145 23563705

43. Leite AZ, de Rodrigues NC, Gonzaga MI, Paiolo JCC, de Souza CA, Stefanutto NAV, et al. Detection of increased plasma interleukin-6 levels and prevalence of Prevotella copri and Bacteroides vulgatus in the feces of type 2 diabetes patients. Frontiers in Immunology. 2017; 8:1107. doi: 10.3389/fimmu.2017.01107 28966614

44. Fujio-Vejar S, Vasquez Y, Morales P, Magne F, Vera-Wolf P, Ugalde JA, et al. The gut microbiota of healthy Chilean subjects reveals a high abundance of the phylum Verrucomicrobia. Frontiers in Microbiology. 2017; 8:11221. doi: 10.3389/fmicb.2017.01221 28713349

45. Shin NR, Lee JC, Lee HY, Kim MS, Whon TW, Lee MS, et al. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut. 2014; 63(5):727–735. doi: 10.1136/gutjnl-2012-303839 23804561

46. Shen J, Obin MS, Zhao L. The gut microbiota, obesity and insulin resistance. Molecular Aspects of Medicine. 2013. 34(1):39–58. doi: 10.1016/j.mam.2012.11.001 23159341

47. Cani PD, Osto M, Geurts L, Everard A. Involvement of gut microbiota in the development of low-grade inflammation and type 2 diabetes associated with obesity. Gut Microbes. 2012; 3(4):279–288. doi: 10.4161/gmic.19625 22572877

48. Vrieze A, Holleman F, Zoetendal EG, De Vos WM, Hoekstra JBL, Nieuwdorp M. The environment within: How gut microbiota may influence metabolism and body composition. Diabetologia. 2010; 53(4):606–613. doi: 10.1007/s00125-010-1662-7 20101384

49. Bäckhed F, Manchester JK, Semenkovich CF, Gordon JI. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proceedings of the National Academy of Sciences of the United States of America. 2007; 104(3):979–984. doi: 10.1073/pnas.0605374104 17210919

50. Cani PD, Possemiers S, Van De Wiele T, Guiot Y, Everard A, Rottier O, et al. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut. 2009; 58(8):1091–1103. doi: 10.1136/gut.2008.165886 19240062

51. Pflughoeft KJ, Versalovic J. Human Microbiome in Health and Disease. Annual Review of Pathology: Mechanisms of Disease. 2012; 7:99–122. doi: 10.1146/annurev-pathol-011811-132421 21910623

52. Afra K, Laupland K, Leal J, Lloyd T, Gregson D. Incidence, risk factors, and outcomes of Fusobacterium species bacteremia. BMC Infectious Diseases. 2013; 13(1):24. doi: 10.1186/1471-2334-13-264 23734900

53. 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(7452):99. doi: 10.1038/nature12198 23719380

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