Top

Published in:

01-12-2021 | Clostridium | Review

Gut microbiota influence in type 2 diabetes mellitus (T2DM)

Authors: A. L. Cunningham, J. W. Stephens, D. A. Harris

Published in: Gut Pathogens | Issue 1/2021

Abstract

A strong and expanding evidence base supports the influence of gut microbiota in human metabolism. Altered glucose homeostasis is associated with altered gut microbiota, and is clearly associated with the development of type 2 diabetes mellitus (T2DM) and associated complications. Understanding the causal association between gut microbiota and metabolic risk has the potential role of identifying susceptible individuals to allow early targeted intervention.

International Diabetes Federation. IDF Diabetes Atlas, Ninth Edition. 2019. https://www.diabetesatlas.org/en/. Accessed 01 Mar 2021.

Bommer C, Sagalova V, Heesemann E, Manne-Goehler J, Atun R, Bärnighausen T, et al. Global economic burden of diabetes in adults: projections from 2015 to 2030. Diabetes Care. 2018;41(5):963–70.CrossRefPubMed

World Health Organisation. Global Report on Diabetes. 2016. https://www.who.int/publications/i/item/9789241565257. Accessed 01 Mar 2021.

United Nations General Assembly. Political declaration of the high-level meeting of the general assembly on the prevention and control of non-communicable diseases. 2012. https://www.who.int/nmh/events/un_ncd_summit2011/political_declaration_en.pdf. Accessed 01 Mar 2021.

: Diabetes UK, Facts and Stats (2019). https://www.diabetes.org.uk/resources-s3/2019-02/1362B_Facts%20and%20stats%20Update%20Jan%202019_LOW%20RES_EXTERNAL.pdf. Accessed 01 Mar 2021.

American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2010;33(Suppl 1):S62–9. https://doi.org/10.2337/dc10-S062.CrossRefPubMedCentral

Lederberg J, McCray A. Ome sweet omics—a genealogical treasury of words. Scientist. 2001;15(7):8.

Relman DA, Falkow S. The meaning and impact of the human genome sequence for microbiology. Trends Microbiol. 2001;9(5):206–8. https://doi.org/10.1016/s0966-842x(01)02041-8.CrossRefPubMed

Clavel T, Desmarchelier C, Haller D, et al. Intestinal microbiota in metabolic diseases: from bacterial community structure and functions to species of pathophysiological relevance. Gut Microbes. 2014;5(4):544–51. https://doi.org/10.4161/gmic.29331.CrossRefPubMed

10.

Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI. The human microbiome project. Nature. 2007;449(7164):804–10. https://doi.org/10.1038/nature06244.CrossRefPubMedPubMedCentral

11.

Delzenne NM, Cani PD. Gut microbiota and the pathogenesis of insulin resistance. Curr Diab Rep. 2011;11(3):154–9. https://doi.org/10.1007/s11892-011-0191-1.CrossRefPubMed

12.

Kootte RS, Vrieze A, Holleman F, et al. The therapeutic potential of manipulating gut microbiota in obesity and type 2 diabetes mellitus. Diabetes Obes Metab. 2012;14(2):112–20. https://doi.org/10.1111/j.1463-1326.2011.01483.x.CrossRefPubMed

13.

Blaut M. Ecology and physiology of the intestinal tract. Curr Top Microbiol Immunol. 2013;358:247–72. https://doi.org/10.1007/82_2011_192.CrossRefPubMed

14.

Clemente JC, Ursell LK, Parfrey LW, Knight R. The impact of the gut microbiota on human health: an integrative view. Cell. 2012;148(6):1258–70. https://doi.org/10.1016/j.cell.2012.01.035.CrossRefPubMedPubMedCentral

15.

Kau AL, Ahern PP, Griffin NW, Goodman AL, Gordon JI. Human nutrition, the gut microbiome and the immune system. Nature. 2011;474(7351):327–36. https://doi.org/10.1038/nature10213.CrossRefPubMedPubMedCentral

16.

Guarner F, Malagelada JR. Gut flora in health and disease. Lancet. 2003;361(9356):512–9. https://doi.org/10.1016/S0140-6736(03)12489-0.CrossRefPubMed

17.

Larsen N, Vogensen FK, van den Berg FW, et al. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS ONE. 2010. https://doi.org/10.1371/journal.pone.0009085.CrossRefPubMedPubMedCentral

18.

Qin J, Li Y, Cai Z, 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

19.

He Y, Wu W, Zheng HM, et al. Regional variation limits applications of healthy gut microbiome reference ranges and disease models. Nat Med. 2018;24(10):1532–5. https://doi.org/10.1038/s41591-018-0164-x.CrossRefPubMed

20.

Karlsson FH, Tremaroli V, Nookaew I, 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

21.

Forslund K, Hildebrand F, Nielsen T, et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature. 2015;528(7581):262–6. https://doi.org/10.1038/nature15766.CrossRefPubMedPubMedCentral

22.

Zhang F, Wang M, Yang J, et al. Response of gut microbiota in type 2 diabetes to hypoglycemic agents. Endocrine. 2019;66(3):485–93. https://doi.org/10.1007/s12020-019-02041-5.CrossRefPubMed

23.

Sedighi M, Razavi S, Navab-Moghadam F, et al. Comparison of gut microbiota in adult patients with type 2 diabetes and healthy individuals. Microb Pathog. 2017;111:362–9. https://doi.org/10.1016/j.micpath.2017.08.038.CrossRefPubMed

24.

Komaroff AL. The microbiome and risk for obesity and diabetes. JAMA. 2017;317(4):355–6. https://doi.org/10.1001/jama.2016.20099.CrossRefPubMed

25.

Zhao L, Lou H, Peng Y, Chen S, Zhang Y, Li X. Comprehensive relationships between gut microbiome and faecal metabolome in individuals with type 2 diabetes and its complications. Endocrine. 2019;66(3):526–37. https://doi.org/10.1007/s12020-019-02103-8.CrossRefPubMed

26.

Lambeth SM, Carson T, Lowe J, et al. Composition, diversity and abundance of gut microbiome in prediabetes and type 2 diabetes. J Diabetes Obes. 2015;2(3):1–7. https://doi.org/10.15436/2376-0949.15.031.CrossRefPubMedPubMedCentral

27.

Furet JP, Kong LC, Tap J, et al. Differential adaptation of human gut microbiota to bariatric surgery-induced weight loss: links with metabolic and low-grade inflammation markers. Diabetes. 2010;59(12):3049–57. https://doi.org/10.2337/db10-0253.CrossRefPubMedPubMedCentral

28.

Zhang X, Shen D, Fang Z, 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

29.

Canfora EE, Jocken JW, Blaak EE. Short-chain fatty acids in control of body weight and insulin sensitivity. Nat Rev Endocrinol. 2015;11(10):577–91. https://doi.org/10.1038/nrendo.2015.128.CrossRefPubMed

30.

Kelly CJ, Zheng L, Campbell EL, et al. Crosstalk between microbiota-derived short-chain fatty acids and intestinal epithelial HIF augments tissue barrier function. Cell Host Microbe. 2015;17(5):662–71. https://doi.org/10.1016/j.chom.2015.03.005.CrossRefPubMedPubMedCentral

31.

Pedersen HK, Gudmundsdottir V, Nielsen HB, et al. Human gut microbes impact host serum metabolome and insulin sensitivity. Nature. 2016;535(7612):376–81. https://doi.org/10.1038/nature18646.CrossRefPubMed

32.

de Mello VD, Paananen J, Lindström J, et al. Indolepropionic acid and novel lipid metabolites are associated with a lower risk of type 2 diabetes in the Finnish Diabetes Prevention Study. Sci Rep. 2017;7:46337. https://doi.org/10.1038/srep46337.CrossRefPubMedPubMedCentral

33.

Wu X, Ma C, Han L, et al. Molecular characterisation of the faecal microbiota in patients with type II diabetes. Curr Microbiol. 2010;61(1):69–78. https://doi.org/10.1007/s00284-010-9582-9.CrossRefPubMed

34.

Sato J, Kanazawa A, Ikeda F, 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

35.

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. https://doi.org/10.1007/s00125-007-0791-0.CrossRefPubMed

36.

Amar J, Chabo C, Waget A, et al. Intestinal mucosal adherence and translocation of commensal bacteria at the early onset of type 2 diabetes: molecular mechanisms and probiotic treatment. EMBO Mol Med. 2011;3(9):559–72. https://doi.org/10.1002/emmm.201100159.CrossRefPubMedPubMedCentral

37.

O’Mahony D, Murphy S, Boileau T, et al. Bifidobacterium animalis AHC7 protects against pathogen-induced NF-κB activation in vivo. BMC Immunol. 2010;11:63. https://doi.org/10.1186/1471-2172-11-63.CrossRefPubMedPubMedCentral

38.

Jia L, Li D, Feng N, et al. Anti-diabetic effects of clostridium butyricum CGMCC0313.1 through promoting the growth of gut butyrate-producing bacteria in type 2 diabetic mice. Sci Rep. 2017;7(1):7046. https://doi.org/10.1038/s41598-017-07335-0.CrossRefPubMedPubMedCentral

39.

de Goffau MC, Luopajärvi K, Knip M, et al. Fecal microbiota composition differs between children with β-cell autoimmunity and those without. Diabetes. 2013;62(4):1238–44. https://doi.org/10.2337/db12-0526.CrossRefPubMedPubMedCentral

40.

Depommier C, Everard A, Druart C, et al. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat Med. 2019;25(7):1096–103. https://doi.org/10.1038/s41591-019-0495-2.CrossRefPubMedPubMedCentral

41.

Everard A, Belzer C, Geurts L, 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

42.

Allin KH, Tremaroli V, Caesar R, et al. Aberrant intestinal microbiota in individuals with prediabetes. Diabetologia. 2018;61(4):810–20. https://doi.org/10.1007/s00125-018-4550-1.CrossRefPubMedPubMedCentral

43.

American Diabetes Association. 2. classification and diagnosis of diabetes: standards of medical care in diabetes-2020. Diabetes Care. 2020;43(Suppl 1):S14–31. https://doi.org/10.2337/dc20-S002.CrossRef

44.

American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2014;37(Suppl 1):S81–90. https://doi.org/10.2337/dc14-S081.CrossRef

45.

Vaarala O, Atkinson MA, Neu J. The, “perfect storm” for type 1 diabetes: the complex interplay between intestinal microbiota, gut permeability, and mucosal immunity. Diabetes. 2008;57(10):2555–62. https://doi.org/10.2337/db08-0331.CrossRefPubMedPubMedCentral

46.

Brown CT, Davis-Richardson AG, Giongo A, et al. Gut microbiome metagenomics analysis suggests a functional model for the development of autoimmunity for type 1 diabetes. PLoS ONE. 2011;6(10):e25792. https://doi.org/10.1371/journal.pone.0025792.CrossRefPubMedPubMedCentral

47.

Vatanen T, Franzosa EA, Schwager R, et al. The human gut microbiome in early-onset type 1 diabetes from the TEDDY study. Nature. 2018;562(7728):589–94. https://doi.org/10.1038/s41586-018-0620-2.CrossRefPubMedPubMedCentral

48.

Stewart CJ, Ajami NJ, O’Brien JL, et al. Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature. 2018;562(7728):583–8. https://doi.org/10.1038/s41586-018-0617-x.CrossRefPubMedPubMedCentral

49.

Uusitalo U, Liu X, Yang J, et al. Association of early exposure of probiotics and islet autoimmunity in the TEDDY study. JAMA Pediatr. 2016;170(1):20–8. https://doi.org/10.1001/jamapediatrics.2015.2757.CrossRefPubMedPubMedCentral

50.

Sohail MU, Althani A, Anwar H, Rizzi R, Marei HE. Role of the gastrointestinal tract microbiome in the pathophysiology of diabetes mellitus. J Diabetes Res. 2017;2017:9631435. https://doi.org/10.1155/2017/9631435.CrossRefPubMedPubMedCentral

51.

Meijnikman AS, Gerdes VE, Nieuwdorp M, Herrema H. Evaluating causality of gut microbiota in obesity and diabetes in humans. Endocr Rev. 2018;39(2):133–53. https://doi.org/10.1210/er.2017-00192.CrossRefPubMed

52.

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

53.

Falony G, Joossens M, Vieira-Silva S, et al. Population-level analysis of gut microbiome variation. Science. 2016;352(6285):560–4. https://doi.org/10.1126/science.aad3503.CrossRefPubMed

54.

Murphy EF, Cotter PD, Healy S, et al. Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models. Gut. 2010;59(12):1635–42. https://doi.org/10.1136/gut.2010.215665.CrossRefPubMed

55.

Jernberg C, Löfmark S, Edlund C, Jansson JK. Long-term ecological impacts of antibiotic administration on the human intestinal microbiota. ISME J. 2007;1(1):56–66. https://doi.org/10.1038/ismej.2007.3.CrossRefPubMed

56.

Mikkelsen KH, Knop FK, Frost M, Hallas J, Pottegård A. Use of antibiotics and risk of type 2 diabetes: a population-based case-control study. J Clin Endocrinol Metab. 2015;100(10):3633–40. https://doi.org/10.1210/jc.2015-2696.CrossRefPubMedPubMedCentral

57.

Vrieze A, Out C, Fuentes S, et al. Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity. J Hepatol. 2014;60(4):824–31. https://doi.org/10.1016/j.jhep.2013.11.034.CrossRefPubMed

58.

Montandon SA, Jornayvaz FR. Effects of antidiabetic drugs on gut microbiota composition. Genes (Basel). 2017;8(10):250. https://doi.org/10.3390/genes8100250.CrossRefPubMedCentral

59.

Shin NR, Lee JC, Lee HY, 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):727–35. https://doi.org/10.1136/gutjnl-2012-303839.CrossRefPubMed

60.

Wu H, Esteve E, Tremaroli V, et al. Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nat Med. 2017;23(7):850–8. https://doi.org/10.1038/nm.4345.CrossRefPubMed

61.

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

62.

Sun L, Xie C, Wang G, et al. Gut microbiota and intestinal FXR mediate the clinical benefits of metformin. Nat Med. 2018;24(12):1919–29. https://doi.org/10.1038/s41591-018-0222-4.CrossRefPubMedPubMedCentral

63.

Sheng Y, Zheng S, Ma T, et al. Mulberry leaf alleviates streptozotocin-induced diabetic rats by attenuating NEFA signaling and modulating intestinal microflora. Sci Rep. 2017;7(1):12041. https://doi.org/10.1038/s41598-017-12245-2.CrossRefPubMedPubMedCentral

64.

van Bommel EJM, Herrema H, Davids M, Kramer MHH, Nieuwdorp M, van Raalte DH. Effects of 12-week treatment with dapagliflozin and gliclazide on faecal microbiome: results of a double-blind randomized trial in patients with type 2 diabetes. Diabetes Metab. 2020;46(2):164–8. https://doi.org/10.1016/j.diabet.2019.11.005.CrossRefPubMed

65.

Wang L, Li P, Tang Z, Yan X, Feng B. Structural modulation of the gut microbiota and the relationship with body weight: compared evaluation of liraglutide and saxagliptin treatment. Sci Rep. 2016;6:33251. https://doi.org/10.1038/srep33251.CrossRefPubMedPubMedCentral

66.

Zhao L, Chen Y, Xia F, et al. A glucagon-like peptide-1 receptor agonist lowers weight by modulating the structure of gut microbiota. Front Endocrinol (Lausanne). 2018;9:233. https://doi.org/10.3389/fendo.2018.00233.CrossRefPubMedPubMedCentral

67.

Wang Z, Saha S, Van Horn S, et al. Gut microbiome differences between metformin- and liraglutide-treated T2DM subjects. Endocrinol Diabetes Metab. 2017;1(1):e00009. https://doi.org/10.1002/edm2.9.CrossRefPubMedPubMedCentral

68.

Gérard C, Vidal H. Impact of gut microbiota on host glycemic control. Front Endocrinol (Lausanne). 2019;10:29. https://doi.org/10.3389/fendo.2019.00029.CrossRefPubMedPubMedCentral

69.

Roy CC, Kien CL, Bouthillier L, Levy E. Short-chain fatty acids: ready for prime time? Nutr Clin Pract. 2006;21(4):351–66. https://doi.org/10.1177/0115426506021004351.CrossRefPubMed

70.

Mortensen PB, Clausen MR. Short-chain fatty acids in the human colon: relation to gastrointestinal health and disease. Scand J Gastroenterol Suppl. 1996;216:132–48. https://doi.org/10.3109/00365529609094568.CrossRefPubMed

71.

Ohira H, Tsutsui W, Fujioka Y. Are short chain fatty acids in gut microbiota defensive players for inflammation and atherosclerosis? J Atheroscler Thromb. 2017;24(7):660–72. https://doi.org/10.5551/jat.RV17006.CrossRefPubMedPubMedCentral

72.

Dai ZL, Wu G, Zhu WY. Amino acid metabolism in intestinal bacteria: links between gut ecology and host health. Front Biosci (Landmark Ed). 2011;16:1768–86. https://doi.org/10.2741/3820.CrossRefPubMed

73.

Macfarlane GT, Allison C, Gibson SA, Cummings JH. Contribution of the microflora to proteolysis in the human large intestine. J Appl Bacteriol. 1988;64(1):37–46. https://doi.org/10.1111/j.1365-2672.1988.tb02427.x.CrossRefPubMed

74.

Koh A, De Vadder F, Kovatcheva-Datchary P, Bäckhed F. From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell. 2016;165(6):1332–45. https://doi.org/10.1016/j.cell.2016.05.041.CrossRefPubMed

75.

Cummings JH. Short chain fatty acids in the human colon. Gut. 1981;22(9):763–79. https://doi.org/10.1136/gut.22.9.763.CrossRefPubMedPubMedCentral

76.

Baxter NT, Lesniak NA, Sinani H, Schloss PD, Koropatkin NM. The glucoamylase inhibitor acarbose has a diet-dependent and reversible effect on the murine gut microbiome. mSphere. 2019;4(1):e00528-e618. https://doi.org/10.1128/mSphere.00528-18.CrossRefPubMedPubMedCentral

77.

Tazoe H, Otomo Y, Kaji I, Tanaka R, Karaki SI, Kuwahara A. Roles of short-chain fatty acids receptors, GPR41 and GPR43 on colonic functions. J Physiol Pharmacol. 2008;59(Suppl 2):251–62.PubMed

78.

Tolhurst G, Heffron H, Lam YS, et al. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes. 2012;61(2):364–71. https://doi.org/10.2337/db11-1019.CrossRefPubMedPubMedCentral

79.

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

80.

Amato A, Cinci L, Rotondo A, et al. Peripheral motor action of glucagon-like peptide-1 through enteric neuronal receptors. Neurogastroenterol Motil. 2010;22(6):664-e203. https://doi.org/10.1111/j.1365-2982.2010.01476.x.CrossRefPubMed

81.

De Vadder F, Kovatcheva-Datchary P, Goncalves D, et al. Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell. 2014;156(1–2):84–96. https://doi.org/10.1016/j.cell.2013.12.016.CrossRefPubMed

82.

Al-Lahham SH, Peppelenbosch MP, Roelofsen H, Vonk RJ, Venema K. Biological effects of propionic acid in humans; metabolism, potential applications and underlying mechanisms. Biochim Biophys Acta. 2010;1801(11):1175–83. https://doi.org/10.1016/j.bbalip.2010.07.007.CrossRefPubMed

83.

Perry RJ, Peng L, Barry NA, et al. Acetate mediates a microbiome-brain-β-cell axis to promote metabolic syndrome. Nature. 2016;534(7606):213–7. https://doi.org/10.1038/nature18309.CrossRefPubMedPubMedCentral

84.

Gao Z, Yin J, Zhang J, et al. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes. 2009;58(7):1509–17. https://doi.org/10.2337/db08-1637.CrossRefPubMedPubMedCentral

85.

He J, Zhang P, Shen L, et al. Short-chain fatty acids and their association with signalling pathways in inflammation, glucose and lipid metabolism. Int J Mol Sci. 2020;21(17):6356. https://doi.org/10.3390/ijms21176356.CrossRefPubMedCentral

86.

Salminen S, Bouley C, Boutron-Ruault MC, et al. Functional food science and gastrointestinal physiology and function. Br J Nutr. 1998;80(Suppl 1):S147–71. https://doi.org/10.1079/bjn19980108.CrossRefPubMed

87.

Frost G, Sleeth ML, Sahuri-Arisoylu M, et al. The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nat Commun. 2014;5:3611. https://doi.org/10.1038/ncomms4611.CrossRefPubMed

88.

Hamer HM, Jonkers D, Venema K, Vanhoutvin S, Troost FJ, Brummer RJ. Review article: the role of butyrate on colonic function. Aliment Pharmacol Ther. 2008;27(2):104–19. https://doi.org/10.1111/j.1365-2036.2007.03562.x.CrossRefPubMed

89.

Sanna S, van Zuydam NR, Mahajan A, et al. Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases. Nat Genet. 2019;51(4):600–5. https://doi.org/10.1038/s41588-019-0350-x.CrossRefPubMedPubMedCentral

90.

den Besten G, Lange K, Havinga R, et al. Gut-derived short-chain fatty acids are vividly assimilated into host carbohydrates and lipids. Am J Physiol Gastrointest Liver Physiol. 2013;305(12):G900–10. https://doi.org/10.1152/ajpgi.00265.2013.CrossRef

91.

Bloemen JG, Olde Damink SW, Venema K, Buurman WA, Jalan R, Dejong CH. Short chain fatty acids exchange: Is the cirrhotic, dysfunctional liver still able to clear them? Clin Nutr. 2010;29(3):365–9. https://doi.org/10.1016/j.clnu.2009.10.002.CrossRefPubMed

92.

Pingitore A, Chambers ES, Hill T, et al. The diet-derived short chain fatty acid propionate improves beta-cell function in humans and stimulates insulin secretion from human islets in vitro. Diabetes Obes Metab. 2017;19(2):257–65. https://doi.org/10.1111/dom.12811.CrossRefPubMed

93.

Chambers ES, Viardot A, Psichas A, 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

94.

Zhao L, Zhang F, Ding 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.CrossRefPubMed

95.

Vitale M, Giacco R, Laiola M, et al. Acute and chronic improvement in postprandial glucose metabolism by a diet resembling the traditional Mediterranean dietary pattern: can SCFAs play a role? Clin Nutr. 2021;40(2):428–37. https://doi.org/10.1016/j.clnu.2020.05.025.CrossRefPubMed

96.

De Vadder F, Kovatcheva-Datchary P, Zitoun C, Duchampt A, Bäckhed F, Mithieux G. Microbiota-produced succinate improves glucose homeostasis via intestinal gluconeogenesis. Cell Metab. 2016;24(1):151–7. https://doi.org/10.1016/j.cmet.2016.06.013.CrossRefPubMed

97.

Venter CS, Vorster HH, Cummings JH. Effects of dietary propionate on carbohydrate and lipid metabolism in healthy volunteers. Am J Gastroenterol. 1990;85(5):549–53.PubMed

98.

Wang TJ, Larson MG, Vasan RS, 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

99.

Chimerel C, Emery E, Summers DK, Keyser U, Gribble FM, Reimann F. Bacterial metabolite indole modulates incretin secretion from intestinal enteroendocrine L cells. Cell Rep. 2014;9(4):1202–8. https://doi.org/10.1016/j.celrep.2014.10.032.CrossRefPubMedPubMedCentral

100.

Gribble FM, Reimann F. Function and mechanisms of enteroendocrine cells and gut hormones in metabolism. Nat Rev Endocrinol. 2019;15(4):226–37. https://doi.org/10.1038/s41574-019-0168-8.CrossRefPubMed

101.

Koh A, Molinaro A, Ståhlman M, et al. Microbially produced imidazole propionate impairs insulin signaling through mTORC1. Cell. 2018;175(4):947-961.e17. https://doi.org/10.1016/j.cell.2018.09.055.CrossRefPubMed

102.

Swann JR, Want EJ, Geier FM, et al. Systemic gut microbial modulation of bile acid metabolism in host tissue compartments. Proc Natl Acad Sci U S A. 2011;108(Suppl 1):4523–30. https://doi.org/10.1073/pnas.1006734107.CrossRefPubMed

103.

Sayin SI, Wahlström A, Felin J, et al. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab. 2013;17(2):225–35. https://doi.org/10.1016/j.cmet.2013.01.003.CrossRefPubMed

104.

Lazar V, Ditu LM, Pircalabioru GG, et al. Gut microbiota, host organism, and diet trialogue in diabetes and obesity. Front Nutr. 2019;6:21. https://doi.org/10.3389/fnut.2019.00021.CrossRefPubMedPubMedCentral

105.

Thomas C, Gioiello A, Noriega L, et al. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab. 2009;10(3):167–77. https://doi.org/10.1016/j.cmet.2009.08.001.CrossRefPubMedPubMedCentral

106.

Kurdi P, Kawanishi K, Mizutani K, Yokota A. Mechanism of growth inhibition by free bile acids in lactobacilli and bifidobacteria. J Bacteriol. 2006;188(5):1979–86. https://doi.org/10.1128/JB.188.5.1979-1986.2006.CrossRefPubMedPubMedCentral

107.

Nicholson JK, Holmes E, Kinross J, et al. Host-gut microbiota metabolic interactions. Science. 2012;336(6086):1262–7. https://doi.org/10.1126/science.1223813.CrossRefPubMed

108.

Yamagata K, Daitoku H, Shimamoto Y, et al. Bile acids regulate gluconeogenic gene expression via small heterodimer partner-mediated repression of hepatocyte nuclear factor 4 and Foxo1. J Biol Chem. 2004;279(22):23158–65. https://doi.org/10.1074/jbc.M314322200.CrossRefPubMed

109.

Kir S, Beddow SA, Samuel VT, et al. FGF19 as a postprandial, insulin-independent activator of hepatic protein and glycogen synthesis. Science. 2011;331(6024):1621–4. https://doi.org/10.1126/science.1198363.CrossRefPubMedPubMedCentral

110.

Cicione C, Degirolamo C, Moschetta A. Emerging role of fibroblast growth factors 15/19 and 21 as metabolic integrators in the liver. Hepatology. 2012;56(6):2404–11. https://doi.org/10.1002/hep.25929.CrossRefPubMed

111.

Potthoff MJ, Kliewer SA, Mangelsdorf DJ. Endocrine fibroblast growth factors 15/19 and 21: from feast to famine. Genes Dev. 2012;26(4):312–24. https://doi.org/10.1101/gad.184788.111.CrossRefPubMedPubMedCentral

112.

Sonne DP, Hansen M, Knop FK. Bile acid sequestrants in type 2 diabetes: potential effects on GLP1 secretion. Eur J Endocrinol. 2014;171(2):R47–65. https://doi.org/10.1530/EJE-14-0154.CrossRefPubMed

113.

Hansen M, Sonne DP, Knop FK. Bile acid sequestrants: glucose-lowering mechanisms and efficacy in type 2 diabetes. Curr Diab Rep. 2014;14(5):482. https://doi.org/10.1007/s11892-014-0482-4.CrossRefPubMed

114.

Hartmann P, Chen P, Wang HJ, et al. Deficiency of intestinal mucin-2 ameliorates experimental alcoholic liver disease in mice. Hepatology. 2013;58(1):108–19. https://doi.org/10.1002/hep.26321.CrossRefPubMed

115.

Everard A, Cani PD. Diabetes, obesity and gut microbiota. Best Pract Res Clin Gastroenterol. 2013;27(1):73–83. https://doi.org/10.1016/j.bpg.2013.03.007.CrossRefPubMed

116.

Cani PD, Possemiers S, Van de Wiele T, 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):1091–103. https://doi.org/10.1136/gut.2008.165886.CrossRefPubMed

117.

Hansen J, Gulati A, Sartor RB. The role of mucosal immunity and host genetics in defining intestinal commensal bacteria. Curr Opin Gastroenterol. 2010;26(6):564–71. https://doi.org/10.1097/MOG.0b013e32833f1195.CrossRefPubMedPubMedCentral

118.

Dandona P, Aljada A, Bandyopadhyay A. Inflammation: the link between insulin resistance, obesity and diabetes. Trends Immunol. 2004;25(1):4–7. https://doi.org/10.1016/j.it.2003.10.013.CrossRefPubMed

119.

Reyes M, Quintanilla C, Burrows R, Blanco E, Cifuentes M, Gahagan S. Obesity is associated with acute inflammation in a sample of adolescents. Pediatr Diabetes. 2015;16(2):109–16. https://doi.org/10.1111/pedi.12129.CrossRefPubMed

120.

Delzenne NM, Cani PD, Everard A, Neyrinck AM, Bindels LB. Gut microorganisms as promising targets for the management of type 2 diabetes. Diabetologia. 2015;58(10):2206–17. https://doi.org/10.1007/s00125-015-3712-7.CrossRefPubMed

121.

Devaraj S, Hemarajata P, Versalovic J. The human gut microbiome and body metabolism: implications for obesity and diabetes. Clin Chem. 2013;59(4):617–28. https://doi.org/10.1373/clinchem.2012.187617.CrossRefPubMedPubMedCentral

122.

Ley RE. Obesity and the human microbiome. Curr Opin Gastroenterol. 2010;26(1):5–11. https://doi.org/10.1097/MOG.0b013e328333d751.CrossRefPubMed

123.

Cani PD, Bibiloni R, Knauf C, et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes. 2008;57(6):1470–81. https://doi.org/10.2337/db07-1403.CrossRefPubMed

124.

Chen X, Devaraj S. Gut microbiome in obesity, metabolic syndrome, and diabetes. Curr Diab Rep. 2018;18(12):129. https://doi.org/10.1007/s11892-018-1104-3.CrossRefPubMed

125.

Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, Edberg S, Medzhitov R. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell. 2004;118(2):229–41. https://doi.org/10.1016/j.cell.2004.07.002.CrossRefPubMed

126.

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.CrossRefPubMedPubMedCentral

127.

Grabstein KH, Eisenman J, Shanebeck K, et al. Cloning of a T cell growth factor that interacts with the beta chain of the interleukin-2 receptor. Science. 1994;264(5161):965–8. https://doi.org/10.1126/science.8178155.CrossRefPubMed

128.

Sun H, Liu D. Hydrodynamic delivery of interleukin 15 gene promotes resistance to high fat diet-induced obesity, fatty liver and improves glucose homeostasis. Gene Ther. 2015;22(4):341–7. https://doi.org/10.1038/gt.2014.114.CrossRefPubMed

129.

Barra NG, Reid S, MacKenzie R, et al. Interleukin-15 contributes to the regulation of murine adipose tissue and human adipocytes. Obesity (Silver Spring). 2010;18(8):1601–7. https://doi.org/10.1038/oby.2009.445.CrossRef

130.

Rui L, Yuan M, Frantz D, Shoelson S, White MF. SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2. J Biol Chem. 2002;277(44):42394–8. https://doi.org/10.1074/jbc.C200444200.CrossRefPubMed

131.

Zhao L. The gut microbiota and obesity: from correlation to causality. Nat Rev Microbiol. 2013;11(9):639–47. https://doi.org/10.1038/nrmicro3089.CrossRefPubMed

132.

Kim M, Qie Y, Park J, Kim CH. Gut microbial metabolites fuel host antibody responses. Cell Host Microbe. 2016;20(2):202–14. https://doi.org/10.1016/j.chom.2016.07.001.CrossRefPubMedPubMedCentral

133.

Donath MY. Targeting inflammation in the treatment of type 2 diabetes: time to start. Nat Rev Drug Discov. 2014;13(6):465–76. https://doi.org/10.1038/nrd4275.CrossRefPubMed

134.

Larsen CM, Faulenbach M, Vaag A, et al. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med. 2007;356(15):1517–26. https://doi.org/10.1056/NEJMoa065213.CrossRefPubMed

135.

Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA. 2001;286(3):327–34. https://doi.org/10.1001/jama.286.3.327.CrossRefPubMed

136.

Rotter V, Nagaev I, Smith U. Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factor-alpha, overexpressed in human fat cells from insulin-resistant subjects. J Biol Chem. 2003;278(46):45777–84. https://doi.org/10.1074/jbc.M301977200.CrossRefPubMed

137.

Salgaço MK, Oliveira LGS, Costa GN, Bianchi F, Sivieri K. Relationship between gut microbiota, probiotics, and type 2 diabetes mellitus. Appl Microbiol Biotechnol. 2019;103(23–24):9229–38. https://doi.org/10.1007/s00253-019-10156-y.CrossRefPubMed

138.

Panwar H, Rashmi HM, Batish VK, Grover S. Probiotics as potential biotherapeutics in the management of type 2 diabetes—prospects and perspectives. Diabetes Metab Res Rev. 2013;29(2):103–12. https://doi.org/10.1002/dmrr.2376.CrossRefPubMed

139.

Hill C, Guarner F, Reid G, et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11(8):506–14. https://doi.org/10.1038/nrgastro.2014.66.CrossRefPubMed

140.

Louis P, Flint HJ, Michel C. How to manipulate the microbiota: prebiotics. Adv Exp Med Biol. 2016;902:119–42. https://doi.org/10.1007/978-3-319-31248-4_9.CrossRefPubMed

141.

Swanson KS, Gibson GR, Hutkins R, et al. The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics. Nat Rev Gastroenterol Hepatol. 2020;17(11):687–701. https://doi.org/10.1038/s41575-020-0344-2.CrossRefPubMedPubMedCentral

142.

Balakumar M, Prabhu D, Sathishkumar C, et al. Improvement in glucose tolerance and insulin sensitivity by probiotic strains of Indian gut origin in high-fat diet-fed C57BL/6J mice. Eur J Nutr. 2018;57(1):279–95. https://doi.org/10.1007/s00394-016-1317-7.CrossRefPubMed

143.

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(1):30. https://doi.org/10.1186/s12967-020-02213-2.CrossRefPubMedPubMedCentral

144.

Andreasen AS, Larsen N, Pedersen-Skovsgaard T, 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/S0007114510002874.CrossRefPubMed

145.

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

146.

Wang L, Yang H, Huang H, et al. Inulin-type fructans supplementation improves glycemic control for the prediabetes and type 2 diabetes populations: results from a GRADE-assessed systematic review and dose-response meta-analysis of 33 randomized controlled trials. J Transl Med. 2019;17(1):410. https://doi.org/10.1186/s12967-019-02159-0.CrossRefPubMedPubMedCentral

147.

Birkeland E, Gharagozlian S, Birkeland KI, et al. Prebiotic effect of inulin-type fructans on faecal microbiota and short-chain fatty acids in type 2 diabetes: a randomised controlled trial. Eur J Nutr. 2020;59(7):3325–38. https://doi.org/10.1007/s00394-020-02282-5.CrossRefPubMedPubMedCentral

148.

Pedersen C, Gallagher E, Horton F, et al. Host-microbiome interactions in human type 2 diabetes following prebiotic fibre (galacto-oligosaccharide) intake. Br J Nutr. 2016;116(11):1869–77. https://doi.org/10.1017/S0007114516004086.CrossRefPubMed

149.

Sheth M, Chand V, Thakuria A. Inflated levels of SCFA, Bifidobacteria and Lactobacillus improves the status of pre hypertension and type 2 diabetes mellitus in subjects residing in north east India—a randomized control trial with synbiotic supplementation. Int J Curr Pharm Res. 2015;7:33–6.

150.

Allegretti JR, Kassam Z, Osman M, Budree S, Fischer M, Kelly CR. The 5D framework: a clinical primer for fecal microbiota transplantation to treat Clostridium difficile infection. Gastrointest Endosc. 2018;87(1):18–29. https://doi.org/10.1016/j.gie.2017.05.036.CrossRefPubMed

151.

Tariq R, Pardi DS, Bartlett MG, Khanna S. Low cure rates in controlled trials of fecal microbiota transplantation for recurrent Clostridium difficile infection: a systematic review and meta-analysis. Clin Infect Dis. 2019;68(8):1351–8. https://doi.org/10.1093/cid/ciy721.CrossRefPubMed

152.

Lee P, Yacyshyn BR, Yacyshyn MB. Gut microbiota and obesity: an opportunity to alter obesity through faecal microbiota transplant (FMT). Diabetes Obes Metab. 2019;21(3):479–90. https://doi.org/10.1111/dom.13561.CrossRefPubMed

153.

Vrieze A, Van Nood E, Holleman F, 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

154.

Kootte RS, Levin E, Salojärvi J, et al. Improvement of insulin sensitivity after lean donor feces in metabolic syndrome is driven by baseline intestinal microbiota composition. Cell Metab. 2017;26(4):611-619.e6. https://doi.org/10.1016/j.cmet.2017.09.008.CrossRefPubMed

Title: Gut microbiota influence in type 2 diabetes mellitus (T2DM)
Authors: A. L. Cunningham
J. W. Stephens
D. A. Harris
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Clostridium
Insulins
Respiratory Microbiota
Diabetes
Insulins
Type 2 Diabetes
Published in: Gut Pathogens / Issue 1/2021
Electronic ISSN: 1757-4749
DOI: https://doi.org/10.1186/s13099-021-00446-0

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

Illustration of figure on mountain summit/© Orapun / Stock.adobe.com, STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2021

Genomic analysis of halophilic bacterium, Lentibacillus sp. CBA3610, derived from human feces

Diversity of 3′ variable region of cagA gene in Helicobacter pylori strains isolated from Chinese population

Ectopic gut colonization: a metagenomic study of the oral and gut microbiome in Crohn’s disease

The glycosyltransferase ST3GAL2 is regulated by miR-615-3p in the intestinal tract of Campylobacter jejuni infected mice

High genetic diversity in Campylobacter concisus isolates from patients with microscopic colitis

Mucosa‐associated cultivable aerobic gut bacterial microbiota among colorectal cancer patients attending at the referral hospitals of Amhara Regional State, Ethiopia

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

Highlights from the ACC 2024 Congress

ACC 2024 Congress Coverage