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09-13-2018 | Pathophysiology | Review | Article

Altered Gut Microbiota in Type 2 Diabetes: Just a Coincidence?

Journal: Current Diabetes Reports

Authors: Antonio Sircana, Luciana Framarin, Nicola Leone, Mara Berrutti, Francesca Castellino, Renato Parente, Franco De Michieli, Elena Paschetta, Giovanni Musso

Publisher: Springer US


Purpose of Review

In the last decade many studies have suggested an association between the altered gut microbiota and multiple systemic diseases including diabetes. In this review, we will discuss potential pathophysiological mechanisms, the latest findings regarding the mechanisms linking gut dysbiosis and type 2 diabetes (T2D), and the results obtained with experimental modulation of microbiota.

Recent Findings

In T2D, gut dysbiosis contributes to onset and maintenance of insulin resistance. Different strategies that reduce dysbiosis can improve glycemic control.


Evidence in animals and humans reveals differences between the gut microbial composition in healthy individuals and those with T2D. Changes in the intestinal ecosystem could cause inflammation, alter intestinal permeability, and modulate metabolism of bile acids, short-chain fatty acids and metabolites that act synergistically on metabolic regulation systems contributing to insulin resistance. Interventions that restore equilibrium in the gut appear to have beneficial effects and improve glycemic control. Future research should examine in detail and in larger studies other possible pathophysiological mechanisms to identify specific pathways modulated by microbiota modulation and identify new potential therapeutic targets.
Harsch IA, Konturek PC. The role of gut microbiota in obesity and type 2 and type 1 diabetes mellitus: new insights into “old” diseases. Med Sci (Basel). 2018 ;6(2). https://​doi.​org/​10.​3390/​medsci6020032.CrossRefPubMedCentral
Lynch SV, Pedersen O. The human intestinal microbiome in health and disease. N Engl J Med. 2016;375(24):2369–79.CrossRefPubMed
Tong M, Li X, Wegener Parfrey L, Roth B, Ippoliti A, Wei B, et al. A modular organization of the human intestinal mucosal microbiota and its association with inflammatory bowel disease. PLoS One. 2013;8:e80702.CrossRefPubMedPubMedCentral
Garrett WS. Cancer and the microbiota. Science. 2015;348:80–6.CrossRefPubMedPubMedCentral
Musso G, Gambino R, Cassader M. Obesity, diabetes, and gut microbiota: the hygiene hypothesis expanded? Diabetes Care. 2010;33(10):2277–84.CrossRefPubMedPubMedCentral
Musso G, Gambino R, Cassader M. Interactions between gut microbiota and host metabolism predisposing to obesity and diabetes. Annu Rev Med. 2011;62:361–80.CrossRefPubMed
Hsiao EY, McBride SW, Hsien S, et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell. 2013;155:1451–63.CrossRefPubMedPubMedCentral
Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, DuGar B, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011;472:57–63.CrossRefPubMedPubMedCentral
Sircana A, De Michieli F, Parente R, Framarin L, Leone N, Berrutti M, Paschetta E, Bongiovanni D, Musso G. Gut microbiota, hypertension and chronic kidney disease: recent advances. Pharmacol Res. 2018. https://​doi.​org/​10.​1016/​j.​phrs.​2018.​01.​013.
Cui L, Morris A, Huang L, Beck JM, Twigg HL 3rd, von Mutius E, et al. The microbiome and the lung. Ann Am Thorac Soc. 2014;11(Suppl 4):S227–32. https://​doi.​org/​10.​1513/​AnnalsATS.​201402-052PL.CrossRefPubMedPubMedCentral
Salamon D, Sroka-Oleksiak A, Kapusta P, Szopa M, Mrozińska S, Ludwig-Słomczyńska AH, et al. Characteristics of the gut microbiota in adult patients with type 1 and 2 diabetes based on the analysis of a fragment of 16S rRNA gene using next-generation sequencing. Pol Arch Intern Med. 2018; https://​doi.​org/​10.​20452/​pamw.​4246.
•• Cani PD, Neyrinck AM, Fava F, et al. Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia. 2007;50(11):2374–83. The first paper describing a possible link between gut microbiota and type 2 diabetes.CrossRefPubMed
D'Argenio V. Human microbiome acquisition and bioinformatic challenges in metagenomic studies. Int J Mol Sci. 2018;19(2). https://​doi.​org/​10.​3390/​ijms19020383.CrossRefPubMedCentral
Jovel J, Patterson J, Wang W, Hotte N, O'Keefe S, Mitchel T, et al. Characterization of the gut microbiome using 16S or shotgun metagenomics. Front Microbiol. 2016;7:459. https://​doi.​org/​10.​3389/​fmicb.​2016.​00459.
Laudadio I, Fulci V, Palone F, Stronati L, Cucchiara S, Carissimi C. Quantitative assessment of shotgun metagenomics and 16S rDNA amplicon sequencing in the study of human gut microbiome. OMICS. 2018;22(4):248–54. https://​doi.​org/​10.​1089/​omi.​2018.​0013.CrossRefPubMed
• Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486(7402):207–14. https://​doi.​org/​10.​1038/​nature11234. Report that delineates the range of structural and functional configurations of microbial communities in healthy population. CrossRef
•• Falony G, Joossens M, Vieira-Silva S, Wang J, Darzi Y, Faust K, et al. Population-level analysis of gut microbiome variation. Science. 2016;352(6285):560–4. https://​doi.​org/​10.​1126/​science.​aad3503. The first two population-based studies published on gut microbiota. CrossRefPubMed
•• Zhernakova A, Kurilshikov A, Bonder MJ, et al. Populationbased metagenomics analysis reveals markers for gut microbiome composition and diversity. Science. 2016;352(6285):565–9. https://​doi.​org/​10.​1126/​science.​aad3369. The first two population-based studies published on gut microbiota.CrossRefPubMedPubMedCentral
Larsen N, Vogensen FK, van den Berg FW, 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;5(2):e9085. https://​doi.​org/​10.​1371/​journal.​pone.​0009085.CrossRefPubMedPubMedCentral
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(7418):55–60. https://​doi.​org/​10.​1038/​nature11450.CrossRefPubMed
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):99–103. https://​doi.​org/​10.​1038/​nature12198.CrossRefPubMed
Tilg H, Moschen AR. Microbiota and diabetes: an evolving relationship 2014;63(9):1513–21. https://​doi.​org/​10.​1136/​gutjnl-2014-306928.CrossRefPubMed
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. https://​doi.​org/​10.​1371/​journal.​pone.​0071108.CrossRefPubMedPubMedCentral
Yassour M, Lim MY, Yun HS, Tickle TL, Sung J, Song YM, et al. Sub-clinical detection of gut microbial biomarkers of obesity and type 2 diabetes. Genome Med. 2016;8(1):17. https://​doi.​org/​10.​1186/​s13073-016-0271-6.CrossRefPubMedPubMedCentral
Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C, Bindels LB, et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci U S A. 2013;110(22):9066–71. https://​doi.​org/​10.​1073/​pnas.​1219451110.CrossRefPubMedPubMedCentral
Pedersen HK, Gudmundsdottir V, Nielsen HB, Hyotylainen T, Nielsen T, Jensen BA, et al. Human gut microbes impact host serum metabolome and insulin sensitivity. Nature. 2016;535(7612):376–81.CrossRefPubMed
McCormack SE, Shaham O, McCarthy MA, Deik AA, Wang TJ, Gerszten RE, et al. Circulating branched-chain amino acid concentrations are associated with obesity and future insulin resistance in children and adolescents. Pediatr Obes. 2013;8(1):52–61. https://​doi.​org/​10.​1111/​j.​2047-6310.​2012.​00087.​x.CrossRefPubMed
Wang TJ, Larson MG, Vasan RS, Cheng S, Rhee EP, McCabe E, et al. Metabolite profiles and the risk of developing diabetes. Nat Med. 2011;17(4):448–53. https://​doi.​org/​10.​1038/​nm.​2307.CrossRefPubMedPubMedCentral
Sato J, Kanazawa A, Ikeda F, Yoshihara T, Goto H, Abe H, et al. Gut dysbiosis and detection of "live gut bacteria" in blood of Japanese patients with type 2 diabetes. Diabetes Care. 2014;37(8):2343–50. https://​doi.​org/​10.​2337/​dc13-2817.CrossRefPubMed
Egshatyan L, Kashtanova D, Popenko A, Tkacheva O, Tyakht A, Alexeev D, et al. Gut microbiota and diet in patients with different glucose tolerance. Endocr Connect. 2016;5(1):1–9. https://​doi.​org/​10.​1530/​EC-15-0094.CrossRefPubMed
Tuovinen E, Keto J, Nikkilä J, Mättö J, Lähteenmäki K. Cytokine response of human mononuclear cells induced by intestinal Clostridium species. Anaerobe. 2013;19:70–6. https://​doi.​org/​10.​1016/​j.​anaerobe.​2012.​11.​002.CrossRefPubMed
Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007;56(7):1761–72.CrossRefPubMed
Li X, Watanabe K, Kimura I. Gut microbiota dysbiosis drives and implies novel therapeutic strategies for diabetes mellitus and related metabolic diseases. Front Immunol. 2017;8:1882. https://​doi.​org/​10.​3389/​fimmu.​2017.​01882.
Saad MJ, Santos A, Prada PO. Linking gut microbiota and inflammation to obesity and insulin resistance. Physiology (Bethesda). 2016;31(4):283–93. https://​doi.​org/​10.​1152/​physiol.​00041.​2015.CrossRef
Liang H, Hussey SE, Sanchez-Avila A, Tantiwong P, Musi N. Effect of lipopolysaccharide on inflammation and insulin action in human muscle. PLoS One. 2013;8(5):e63983. https://​doi.​org/​10.​1371/​journal.​pone.​0063983.CrossRefPubMedPubMedCentral
Lasram MM, Dhouib IB, Annabi A, El Fazaa S, Gharbi N. A review on the possible molecular mechanism of action of N-acetylcysteine against insulin resistance and type-2 diabetes development. Clin Biochem. 2015;48(16–17):1200–8. https://​doi.​org/​10.​1016/​j.​clinbiochem.​2015.​04.​017.CrossRefPubMed
• Zheng J, Yuan X, Zhang C, Jia P, Jiao S, Zhao X, et al. N-Acetyl-cysteine alleviates gut dysbiosis and glucose metabolic disorder in high-fat diet-induced mice. J Diabetes. 2018; https://​doi.​org/​10.​1111/​1753-0407.​12795. The first study evaluating the potential effects of NAC on microbiota in T2DM.
•• Horton F, Wright J, Smith L, Hinton PJ, Robertson MD. Increased intestinal permeability to oral chromium (51 Cr)-EDTA in human type 2 diabetes. Diabet Med. 2014;31(5):559–63. https://​doi.​org/​10.​1111/​dme.​12360. The first demonstration that increased intestinal permeability may be a feature of human Type 2 diabetes. CrossRefPubMed
•• Camargo A, Jimenez-Lucena R, Alcala-Diaz JF, Rangel-Zuñiga OA, Garcia-Carpintero S, Lopez-Moreno J, et al. Postprandial endotoxemia may influence the development of type 2 diabetes mellitus: from the CORDIOPREV study. Clin Nutr. 2018; https://​doi.​org/​10.​1016/​j.​clnu.​2018.​03.​016. Recent study that shows high levels of LPS could precede the development of T2DM.
Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM, et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes. 2008;57:1470–81.CrossRefPubMed
•• Thaiss CA, Levy M, Grosheva I, Zheng D, Soffer E, Blacher E, et al. Hyperglycemia drives intestinal barrier dysfunction and risk for enteric infection. Science. 2018;359(6382):1376–83. https://​doi.​org/​10.​1126/​science.​aar3318. This study proposes a new mechanism responsible for increasing intestinal permeability. CrossRefPubMed
Tan J, McKenzie C, Potamitis M, Thorburn AN, Mackay CR, Macia L. The role of short-chain fatty acids in health and disease. Adv Immunol. 2014;121:91–119. https://​doi.​org/​10.​1016/​B978-0-12-800100-4.​00003-9.CrossRefPubMed
Tang C, Ahmed K, Gille A, Lu S, Gröne HJ, Tunaru S, et al. Loss of FFA2 and FFA3 increases insulin secretion and improves glucose tolerance in type 2 diabetes. Nat Med. 2015;21(2):173–7. https://​doi.​org/​10.​1038/​nm.​3779.CrossRefPubMed
Wan Saudi WS, Sjöblom M. Short-chain fatty acids augment rat duodenal mucosal barrier function. Exp Physiol. 2017;102(7):791–803. https://​doi.​org/​10.​1113/​EP086110.CrossRefPubMed
Priyadarshini M, Navarro G, Layden BT. Gut microbiota: FFAR reaching effects on islets. Endocrinology. 2018;159(6):2495–505. https://​doi.​org/​10.​1210/​en.​2018-00296.CrossRefPubMedPubMedCentral
Chambers ES, Viardot A, Psichas A, Morrison DJ, Murphy KG, Zac-Varghese SE, et al. Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults. Gut. 2015;64(11):1744–54. https://​doi.​org/​10.​1136/​gutjnl-2014-307913.CrossRefPubMed
Grasset E, Puel A, Charpentier J, Collet X, Christensen JE, Tercé F, et al. A specific gut microbiota dysbiosis of type 2 diabetic mice induces GLP-1 resistance through an enteric NO-dependent and gut-brain axis mechanism. Cell Metab. 2017;25(5):1075–1090.e5. https://​doi.​org/​10.​1016/​j.​cmet.​2017.​04.​013.CrossRefPubMed
Mandøe MJ, Hansen KB, Hartmann B, Rehfeld JF, Holst JJ, Hansen HS. The 2-monoacylglycerol moiety of dietary fat appears to be responsible for the fat-induced release of GLP-1 in humans. Am J Clin Nutr. 2015;102(3):548–55. https://​doi.​org/​10.​3945/​ajcn.​115.​106799.CrossRefPubMed
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):1027–31.CrossRefPubMed
Teixeira TF, Grześkowiak Ł, Franceschini SC, Bressan J, Ferreira CL, Peluzio MC. Higher level of faecal SCFA in women correlates with metabolic syndrome risk factors. Br J Nutr. 2013;109(5):914–9. https://​doi.​org/​10.​1017/​S000711451200272​3.CrossRefPubMed
Fiorucci S, Distrutti E. Bile acid-activated receptors, intestinal microbiota, and the treatment of metabolic disorders. Trends Mol Med. 2015;21(11):702–14. https://​doi.​org/​10.​1016/​j.​molmed.​2015.​09.​001.CrossRefPubMed
Yang JY, Kweon MN. The gut microbiota: a key regulator of metabolic diseases. BMB Rep. 2016;49(10):536–41.CrossRefPubMedPubMedCentral
Pathak P, Xie C, Nichols RG, Ferrell JM, Boehme S, Krausz KW, et al. Intestine farnesoid X receptor agonist and the gut microbiota activate G-protein bile acid receptor-1 signaling to improve metabolism. Hepatology. 2018; https://​doi.​org/​10.​1002/​hep.​29857.
Neis EP, Dejong CH, Rensen SS. The role of microbial amino acid metabolism in host metabolism. Nutrients. 2015;7(4):2930–46. https://​doi.​org/​10.​3390/​nu7042930.CrossRefPubMedPubMedCentral
Asghari G, Farhadnejad H, Teymoori F, Mirmiran P, Tohidi M, Azizi F. High dietary intake of branched-chain amino acids is associated with an increased risk of insulin resistance in adults. J Diabetes. 2018;10(5):357–64. https://​doi.​org/​10.​1111/​1753-0407.​12639.CrossRefPubMed
Giesbertz P, Daniel H. Branched-chain amino acids as biomarkers in diabetes. Curr Opin Clin Nutr Metab Care. 2016;19(1):48–54. https://​doi.​org/​10.​1097/​MCO.​0000000000000235​.CrossRefPubMed
Lian K, Du C, Liu Y, Zhu D, Yan W, Zhang H, et al. Impaired adiponectin signaling contributes to disturbed catabolism of branched-chain amino acids in diabetic mice. Diabetes. 2015;64(1):49–59. https://​doi.​org/​10.​2337/​db14-0312.CrossRefPubMed
Gojda J, Straková R, Plíhalová A, Tůma P, Potočková J, Polák J, et al. Increased Incretin but not insulin response after oral versus intravenous branched chain amino acids. Ann Nutr Metab. 2017;70(4):293–302. https://​doi.​org/​10.​1159/​000475604.CrossRefPubMed
Wang Q, Holmes MV, Davey Smith G, Ala-Korpela M. Genetic support for a causal role of insulin resistance on circulating branched-chain amino acids and inflammation. Diabetes Care. 2017;40(12):1779–86. https://​doi.​org/​10.​2337/​dc17-1642.CrossRefPubMed
Bloomgarden Z. Diabetes and branched-chain amino acids: what is the link? J Diabetes. 2018;10(5):350–2. https://​doi.​org/​10.​1111/​1753-0407.​12645.CrossRefPubMed
Shan Z, Sun T, Huang H, Chen S, Chen L, Luo C, et al. Association between microbiota-dependent metabolite trimethylamine-N-oxide and type 2 diabetes. Am J Clin Nutr. 2017;106(3):888–94. https://​doi.​org/​10.​3945/​ajcn.​117.​157107.CrossRefPubMed
Shih DM, Wang Z, Lee R, Meng Y, Che N, Charugundla S, et al. Flavin containing monooxygenase 3 exerts broad effects on glucose and lipid metabolism and atherosclerosis. J Lipid Res. 2015;56(1):22–37. https://​doi.​org/​10.​1194/​jlr.​M051680.CrossRefPubMedPubMedCentral
Heianza Y, Sun D, Li X, DiDonato JA, Bray GA, Sacks FM, et al. Gut microbiota metabolites, amino acid metabolites and improvements in insulin sensitivity and glucose metabolism: the POUNDS Lost trial. Gut. 2018; https://​doi.​org/​10.​1136/​gutjnl-2018-316155.
Richey JM, Woolcott O. Re-visiting the Endocannabinoid system and its therapeutic potential in obesity and associated diseases. Curr Diab Rep. 2017;17(10):99. https://​doi.​org/​10.​1007/​s11892-017-0924-x.CrossRefPubMed
Cani PD, Plovier H, Van Hul M, Geurts L, Delzenne NM, Druart C, et al. Endocannabinoids—at the crossroads between the gut microbiota and host metabolism. Nat Rev Endocrinol. 2016;12(3):133–43. https://​doi.​org/​10.​1038/​nrendo.​2015.​211.CrossRefPubMed
Pereira MA, Kartashov AI, Ebbeling CB, Van Horn L, Slattery ML, Jacobs DR Jr, et al. Fast-food habits, weight gain, and insulin resistance (the CARDIA study): 15-year prospective analysis. Lancet. 2005;365(9453):36–42.CrossRefPubMed
David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505(7484):559–63. https://​doi.​org/​10.​1038/​nature12820.CrossRefPubMed
•• Houghton D, Hardy T, Stewart C, Errington L, Day CP, Trenell MI, et al. Systematic review assessing the effectiveness of dietary intervention on gut microbiota in adults with type 2 diabetes. Diabetologia. 2018; https://​doi.​org/​10.​1007/​s00125-018-4632-0. An up-to-date review on the role of diet in modulating the microbiota and improving diabetes management. CrossRefPubMedCentralPubMed
• Zhao L, Zhang F, Ding X, Wu G, Lam YY, Wang X, et al. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science. 2018;359(6380):1151–6. https://​doi.​org/​10.​1126/​science.​aao5774. Later study that confirms diet as additional approach for the management of DM2. CrossRefPubMed
Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA, Bohlooly-Y M, et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. 2013;341(6145):569–73. https://​doi.​org/​10.​1126/​science.​1241165.CrossRefPubMed
Sanders ME. Probiotics: definition, sources, selection, and uses. Clin Infect Dis. 2008;46:S58–61.CrossRefPubMed
Brunkwall L, Orho-Melander M. The gut microbiome as a target for prevention and treatment of hyperglycaemia in type 2 diabetes: from current human evidence to future possibilities. Diabetologia. 2017;60(6):943–51. https://​doi.​org/​10.​1007/​s00125-017-4278-3.CrossRefPubMedPubMedCentral
Li X, Wang E, Yin B, Fang D, Chen P, Wang G, et al. Effects of Lactobacillus casei CCFM419 on insulin resistance and gut microbiota in type 2 diabetic mice. Benef Microbes. 2017;8(3):421–32. https://​doi.​org/​10.​3920/​BM2016.​0167.CrossRefPubMed
Tian P, Li B, He C, Song W, Hou A, Tian S, et al. Antidiabetic (type 2) effects of Lactobacillus G15 and Q14 in rats through regulation of intestinal permeability and microbiota. Food Funct. 2016;7(9):3789–97.CrossRefPubMed
Daliri EB, Lee BH, Oh DH. Current perspectives on antihypertensive probiotics. Probiotics Antimicrob Proteins. 2017;9(2):91–101.CrossRefPubMed
Andreasen AS, Larsen N, Pedersen-Skovsgaard T, Berg RM, Møller K, Svendsen KD, et al. Effects of Lactobacillus acidophilus NCFM on insulin sensitivity and the systemic inflammatory response in human subjects. Br J Nutr. 2010;104(12):1831–8. https://​doi.​org/​10.​1017/​S000711451000287​4.CrossRefPubMed
Ejtahed HS, Mohtadi-Nia J, Homayouni-Rad A, Niafar M, Asghari-Jafarabadi M, Mofid V. Probiotic yogurt improves antioxidant status in type 2 diabetic patients. Nutrition. 2012;28(5):539–43. https://​doi.​org/​10.​1016/​j.​nut.​2011.​08.​013.CrossRefPubMed
Asemi Z, Zare Z, Shakeri H, Sabihi SS, Esmaillzadeh A. Effect of multispecies probiotic supplements on metabolic profiles, hs-CRP, and oxidative stress in patients with type 2 diabetes. Ann Nutr Metab. 2013;63(1–2):1–9. https://​doi.​org/​10.​1159/​000349922.CrossRefPubMed
Mazloom Z, Yousefinejad A, Dabbaghmanesh MH. Effect of probiotics on lipid profile, glycemic control, insulin action, oxidative stress, and inflammatory markers in patients with type 2 diabetes: a clinical trial. Iran J Med Sci. 2013;38(1):38–43.PubMedPubMedCentral
Ivey KL, Hodgson JM, Kerr DA, Lewis JR, Thompson PL, Prince RL. The effects of probiotic bacteria on glycaemic control in overweight men and women: a randomised controlled trial. Eur J Clin Nutr. 2014;68(4):447–52. https://​doi.​org/​10.​1038/​ejcn.​2013.​294.CrossRefPubMed
Ostadrahimi A, Taghizadeh A, Mobasseri M, Farrin N, Payahoo L, Beyramalipoor Gheshlaghi Z, et al. Effect of probiotic fermented milk (kefir) on glycemic control and lipid profile in type 2 diabetic patients: a randomized double-blind placebo-controlled clinical trial. Iran J Public Health. 2015;44(2):228–37.PubMedPubMedCentral
Simon MC, Strassburger K, Nowotny B, Kolb H, Nowotny P, Burkart V, et al. Intake of Lactobacillus reuteri improves incretin and insulin secretion in glucose-tolerant humans: a proof of concept. Diabetes Care. 2015;38(10):1827–34. https://​doi.​org/​10.​2337/​dc14-2690.CrossRefPubMed
Firouzi S, Majid HA, Ismail A, Kamaruddin NA, Barakatun-Nisak MY. Effect of multi-strain probiotics (multi-strain microbial cell preparation) on glycemic control and other diabetes-related outcomes in people with type 2 diabetes: a randomized controlled trial. Eur J Nutr. 2017;56(4):1535–50. https://​doi.​org/​10.​1007/​s00394-016-1199-8.CrossRefPubMed
Mobini R, Tremaroli V, Ståhlman M, Karlsson F, Levin M, Ljungberg M, et al. Metabolic effects of lactobacillus reuteri DSM 17938 in people with type 2 diabetes: a randomized controlled trial. Diabetes Obes Metab. 2017;19(4):579–89. https://​doi.​org/​10.​1111/​dom.​12861.CrossRefPubMed
Tonucci LB, Olbrich Dos Santos KM, Licursi de Oliveira L, Rocha Ribeiro SM, Duarte Martino HS. Clinical application of probiotics in type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled study. Clin Nutr. 2017;36(1):85–92. https://​doi.​org/​10.​1016/​j.​clnu.​2015.​11.​011.CrossRefPubMed
Feizollahzadeh S, Ghiasvand R, Rezaei A, Khanahmad H, Sadeghi A, Hariri M. Effect of probiotic soy milk on serum levels of adiponectin, inflammatory mediators, lipid profile, and fasting blood glucose among patients with type II diabetes mellitus. Probiotics Antimicrob Proteins. 2017;9(1):41–7. https://​doi.​org/​10.​1007/​s12602-016-9233-y.CrossRefPubMed
Khalili L, Alipour B, Asghari Jafar-Abadi M, Faraji I, Hassanalilou T, Mesgari Abbasi M, Vaghef-Mehrabany E, Alizadeh Sani M. The effects of Lactobacillus casei on glycemic response, serum sirtuin1 and fetuin-a levels in patients with type 2 diabetes mellitus: a randomized controlled trial Iran Biomed J. 2018.
Kobyliak N, Falalyeyeva T, Mykhalchyshyn G, Kyriienko D, Komissarenko I. Effect of alive probiotic on insulin resistance in type 2 diabetes patients: randomized clinical trial. Diabetes Metab Syndr. 2018. https://​doi.​org/​10.​1016/​j.​dsx.​2018.​04.​015.CrossRef
Ruan Y, Sun J, He J, Chen F, Chen R, Chen H. Effect of probiotics on glycemic control: a systematic review and meta-analysis of randomized, controlled trials. PLoS One. 2015;10(7):e0132121. https://​doi.​org/​10.​1371/​journal.​pone.​0132121.CrossRefPubMedPubMedCentral
Li C, Li X, Han H, Cui H, Peng M, Wang G, et al. Effect of probiotics on metabolic profiles in type 2 diabetes mellitus: a meta-analysis of randomized, controlled trials. Medicine (Baltimore). 2016;95(26):e4088. https://​doi.​org/​10.​1097/​MD.​0000000000004088​.CrossRef
Samah S, Ramasamy K, Lim SM, Neoh CF. Probiotics for the management of type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetes Res Clin Pract. 2016;118:172–82. https://​doi.​org/​10.​1016/​j.​diabres.​2016.​06.​014.CrossRefPubMed
Akbari V, Hendijani F. Effects of probiotic supplementation in patients with type 2 diabetes: systematic review and meta-analysis. Nutr Rev. 2016;74(12):774–84.CrossRefPubMed
Yao K, Zeng L, He Q, Wang W, Lei J, Zou X. Effect of probiotics on glucose and lipid metabolism in type 2 diabetes mellitus: a meta-analysis of 12 randomized controlled trials. Med Sci Monit. 2017;23:3044–53.CrossRefPubMedPubMedCentral
de Groot PF, Frissen MN, de Clercq NC, Nieuwdorp M. Fecal microbiota transplantation in metabolic syndrome: history, present and future. Gut Microbes. 2017;8(3):253–67. https://​doi.​org/​10.​1080/​19490976.​2017.​1293224.CrossRefPubMedPubMedCentral
Vrieze A, Van Nood E, Holleman F, Salojärvi J, Kootte RS, Bartelsman JF, et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012;143(4):913–6.e7. https://​doi.​org/​10.​1053/​j.​gastro.​2012.​06.​031.CrossRefPubMed
Devkota S. MICROBIOME. Prescription drugs obscure microbiome analyses. Science. 2016;351(6272):452–3. https://​doi.​org/​10.​1126/​science.​aaf1353.CrossRefPubMed
Rena G, Hardie DG, Pearson ER. The mechanisms of action of metformin. Diabetologia. 2017;60(9):1577–85. https://​doi.​org/​10.​1007/​s00125-017-4342-z.CrossRefPubMedPubMedCentral
Malik F, Mehdi SF, Ali H, Patel P, Basharat A, Kumar A, et al. Is metformin poised for a second career as an antimicrobial? Diabetes Metab Res Rev. 2018;34(4):e2975. https://​doi.​org/​10.​1002/​dmrr.​2975.CrossRefPubMed
Rodriguez J, Hiel S, Delzenne NM. Metformin: old friend, new ways of action-implication of the gut microbiome? Curr Opin Clin Nutr Metab Care. 2018;21(4):294–301. https://​doi.​org/​10.​1097/​MCO.​0000000000000468​.CrossRefPubMed
Montandon SA, Jornayvaz FR. Effects of antidiabetic drugs on gut microbiota composition. Genes (Basel). 2017 ;8(10). https://​doi.​org/​10.​3390/​genes8100250.
Mulla CM, Middelbeek RJW, Patti ME. Mechanisms of weight loss and improved metabolism following bariatric surgery. Ann N Y Acad Sci. 2018;1411(1):53–64. https://​doi.​org/​10.​1111/​nyas.​13409.CrossRefPubMed
Guo Y, Huang ZP, Liu CQ, Qi L, Sheng Y, Zou DJ. Modulation of the gut microbiome: a systematic review of the effect of bariatric surgery. Eur J Endocrinol. 2018;178(1):43–56. https://​doi.​org/​10.​1530/​EJE-17-0403.CrossRefPubMed

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