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13-09-2018 | 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

Abstract

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.

Summary

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.
Literature
1.
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
2.
Lynch SV, Pedersen O. The human intestinal microbiome in health and disease. N Engl J Med. 2016;375(24):2369–79.CrossRefPubMed
3.
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
4.
Garrett WS. Cancer and the microbiota. Science. 2015;348:80–6.CrossRefPubMedPubMedCentral
5.
Musso G, Gambino R, Cassader M. Obesity, diabetes, and gut microbiota: the hygiene hypothesis expanded? Diabetes Care. 2010;33(10):2277–84.CrossRefPubMedPubMedCentral
6.
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
7.
Hsiao EY, McBride SW, Hsien S, et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell. 2013;155:1451–63.CrossRefPubMedPubMedCentral
8.
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
9.
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.
10.
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
11.
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.
12.
•• 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
13.
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
14.
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.
15.
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
16.
• 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
17.
•• 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
18.
•• 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
19.
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
20.
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
21.
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
22.
Tilg H, Moschen AR. Microbiota and diabetes: an evolving relationship 2014;63(9):1513–21. https://​doi.​org/​10.​1136/​gutjnl-2014-306928.CrossRefPubMed
23.
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
24.
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
25.
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
26.
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
27.
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
28.
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
29.
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
30.
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
31.
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
32.
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
33.
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.
34.
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
35.
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
36.
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
37.
• 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.
38.
•• 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
39.
•• 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.
40.
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
41.
•• 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
42.
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
43.
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
44.
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
45.
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
46.
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
47.
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
48.
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
49.
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
50.
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
51.
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
52.
Yang JY, Kweon MN. The gut microbiota: a key regulator of metabolic diseases. BMB Rep. 2016;49(10):536–41.CrossRefPubMedPubMedCentral
53.
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.
54.
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
55.
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
56.
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
57.
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
58.
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
59.
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
60.
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
61.
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
62.
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
63.
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.
64.
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
65.
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
66.
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
67.
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
68.
•• 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
69.
• 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
70.
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
71.
Sanders ME. Probiotics: definition, sources, selection, and uses. Clin Infect Dis. 2008;46:S58–61.CrossRefPubMed
72.
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
73.
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
74.
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
75.
Daliri EB, Lee BH, Oh DH. Current perspectives on antihypertensive probiotics. Probiotics Antimicrob Proteins. 2017;9(2):91–101.CrossRefPubMed
76.
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
77.
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
78.
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
79.
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
80.
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
81.
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
82.
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
83.
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
84.
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
85.
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
86.
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
87.
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.
88.
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
89.
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
90.
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
91.
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
92.
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
93.
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
94.
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
95.
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
96.
Devkota S. MICROBIOME. Prescription drugs obscure microbiome analyses. Science. 2016;351(6272):452–3. https://​doi.​org/​10.​1126/​science.​aaf1353.CrossRefPubMed
97.
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
98.
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
99.
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
100.
Montandon SA, Jornayvaz FR. Effects of antidiabetic drugs on gut microbiota composition. Genes (Basel). 2017 ;8(10). https://​doi.​org/​10.​3390/​genes8100250.
101.
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
102.
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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