Is there a role for gut microbiota in type 1 diabetes pathogenesis?

Annals of Medicine

Volumn 49, Issue 1, 2017, Pages 11-22

  Bibbò, Stefano ^a   Dore, Maria Pina ^a   Pes, Giovanni Mario ^a   Delitala, Giuseppe ^a   Delitala, Alessandro P ^b  

^a UNIVERSITY OF SASSARI   (Italy)

^b UNIVERSITY HOSPITAL OF SASSARI   (Italy)

Author keywords

autoimmunity; Dysbiosis; gut permeability; prevention; probiotic; therapy; type 1 diabetes mellitus

Indexed keywords

ANTIINFECTIVE AGENT; GLUTEN; PROBIOTIC AGENT;

ANIMAL MODEL; BREAST FEEDING; HUMAN; INSULIN DEPENDENT DIABETES MELLITUS; INTESTINE FLORA; INTESTINE MUCOSA PERMEABILITY; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; REVIEW; ANIMAL; AUTOIMMUNITY; DIET; DYSBIOSIS; IMMUNOLOGY; INTESTINE; MICROBIOLOGY; MICROFLORA; PANCREAS ISLET BETA CELL; PATHOLOGY; PATHOPHYSIOLOGY; PERMEABILITY; PHYSIOLOGY;

ANIMALS; AUTOIMMUNITY; DIABETES MELLITUS, TYPE 1; DIET; DYSBIOSIS; GASTROINTESTINAL MICROBIOME; HUMANS; INSULIN-SECRETING CELLS; INTESTINES; MICROBIOTA; MODELS, ANIMAL; PERMEABILITY; PROBIOTICS;

EID: 84999792377     PISSN: 07853890     EISSN: 13652060     Source Type: Journal    
DOI: 10.1080/07853890.2016.1222449     Document Type: Review

References (113)

1. Hollister EB, Gao C, Versalovic J., Compositional and functional features of the gastrointestinal microbiome and their effects on human health. Gastroenterology. 2014;146:1449–58.
2. Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, et al. Diversity of the human intestinal microbial flora. Science. 2005;308:1635–8.
3. Marchesi J, Shanahan F., The normal intestinal microbiota. Curr Opin Infect Dis. 2007;20:508–13.
4. Cani PD., Metabolism in 2013:the gut microbiota manages host metabolism. Nat Rev Endocrinol. 2014;10:74–6.
5. Sekirov I, Russell SL, Antunes LC, Finlay BB., Gut microbiota in health and disease. Physiol Rev. 2010;90:859–904.
6. Longman RS, Yang Y, Diehl GE, Kim SV, Littman DR., Microbiota:host interactions in mucosal homeostasis and systemic autoimmunity. Cold Spring Harb Symp Quant Biol. 2013;78:193–201.
7. Ianiro G, Bibbo S, Gasbarrini A, Cammarota G., Therapeutic modulation of gut microbiota:current clinical applications and future perspectives. Curr Drug Targets. 2014;15:762–70.
8. Cammarota G, Ianiro G, Cianci R, Bibbo S, Gasbarrini A, Curro D., The involvement of gut microbiota in inflammatory bowel disease pathogenesis:potential for therapy. Pharmacol Ther. 2015;149:191–212.
9. Bibbo S, Lopetuso LR, Ianiro G, Di Rienzo T, Gasbarrini A, Cammarota G., Role of microbiota and innate immunity in recurrent Clostridium difficile infection. J Immun Res. 2014:462740.
10. Nieuwdorp M, Gilijamse PW, Pai N, Kaplan LM., Role of the microbiome in energy regulation and metabolism. Gastroenterology. 2014;146:1525–33.
11. Kamada N, Nunez G., Regulation of the immune system by the resident intestinal bacteria. Gastroenterology. 2014;146:1477–88.
12. Vatanen T, Kostic AD, d'Hennezel E, Siljander H, Franzosa EA, Yassour M, et al. Variation in microbiome lps immunogenicity contributes to autoimmunity in humans. Cell. 2016;165:842–53.
13. Kamada N, Seo SU, Chen GY, Nunez G., Role of the gut microbiota in immunity and inflammatory disease. Nat Rev Immunol.2013;13:321–35.
14. Irvine WJ, McCallum CJ, Gray RS, Duncan LJ., Clinical and pathogenic significance of pancreatic-islet-cell antibodies in diabetics treated with oral hypoglycaemic agents. Lancet. 1977;1:1025–7.
15. Pozzilli P, Di Mario U., Autoimmune diabetes not requiring insulin at diagnosis (latent autoimmune diabetes of the adult):definition, characterization, and potential prevention. Diabetes Care. 2001;24:1460–7.
16. Zimmet PZ., The pathogenesis and prevention of diabetes in adults. Genes, autoimmunity, and demography. Diabetes Care. 1995;18:1050–64.
17. Turner R, Stratton I, Horton V, Manley S, Zimmet P, Mackay IR, et al. UKPDS 25:autoantibodies to islet-cell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes. UK Prospective Diabetes Study Group. Lancet. 1997;350:1288–93.
18. Delitala AP, Fanciulli G, Zoledziewska M, Pitzalis M, Pusceddu P, Frongia P, et al. Allelic variant in CTLA4 is associated with thyroid failure and faster β-cell exhaustion in latent autoimmune diabetes in adults. J Diabetes 2015;7:68–73.
19. Pes GM, Delitala AP, Delitala G, Errigo A, Costantino S, Fanciulli G., Phenotypic heterogeneity of latent autoimmune diabetes in adults identified by body composition analysis. Diabetol Metab Syndr. 2014;6:128.
20. Todd JA., Etiology of type 1 diabetes. Immunity. 2010;32:457–67.
21. Bodansky HJ, Staines A, Stephenson C, Haigh D, Cartwright R., Evidence for an environmental effect in the aetiology of insulin dependent diabetes in a transmigratory population. BMJ. 1992;304:1020–2.
22. Dahlquist GG., Viruses and other perinatal exposures as initiating events for beta-cell destruction. Ann Med. 1997;29:413–17.
23. Steck AK, Rewers MJ., Genetics of type 1 diabetes. Clin Chem. 2011;57:176–85.
24. Barrett JC, Clayton DG, Concannon P, Akolkar B, Cooper JD, Erlich HA, et al. Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nature Genet. 2009;41:703–7.
25. Cardwell CR, Stene LC, Ludvigsson J, Rosenbauer J, Cinek O, Svensson J, et al. Breast-feeding and childhood-onset type 1 diabetes:a pooled analysis of individual participant data from 43 observational studies. Diabetes Care. 2012;35:2215–25.
26. Emani R, Asghar MN, Toivonen R, Lauren L, Soderstrom M, Toivola DM, et al. Casein hydrolysate diet controls intestinal T cell activation, free radical production and microbial colonisation in NOD mice. Diabetologia. 2013;56:1781–91.
27. Knip M, Virtanen SM, Seppa K, Ilonen J, Savilahti E, Vaarala O, et al. Dietary intervention in infancy and later signs of beta-cell autoimmunity. N Engl J Med. 2010;363:1900–8.
28. Knip M, Akerblom HK, Becker D, Dosch HM, Dupre J, Fraser W, et al. Hydrolyzed infant formula and early β-cell autoimmunity:a randomized clinical trial. JAMA.2014;311:2279–87.
29. Vahasalo P, Petays T, Knip M, Miettinen A, Saukkonen T, Karjalainen J, et al. Relation between antibodies to islet cell antigens, other autoantigens and cow's milk proteins in diabetic children and unaffected siblings at the clinical manifestation of IDDM. The Childhood Diabetes in Finland Study Group. Autoimmunity. 1996;23:165–74.
30. Saukkonen T, Virtanen SM, Karppinen M, Reijonen H, Ilonen J, Rasanen L, et al. Significance of cow's milk protein antibodies as risk factor for childhood IDDM:interactions with dietary cow's milk intake and HLA-DQB1 genotype. Childhood Diabetes in Finland Study Group. Diabetologia. 1998;41:72–8.
31. Martin JM, Trink B, Daneman D, Dosch HM, Robinson B., Milk proteins in the etiology of insulin-dependent diabetes mellitus (IDDM). Ann Med. 1991;23:447–52.
32. Merriman TR., Type 1 diabetes, the A1 milk hypothesis and vitamin D deficiency. Diabetes Res Clin Prac. 2009;83:149–56.
33. Elliott RB, Reddy SN, Bibby NJ, Kida K., Dietary prevention of diabetes in the non-obese diabetic mouse. Diabetologia. 1988;31:62–4.
34. Muntoni S, Cocco P, Aru G, Cucca F., Nutritional factors and worldwide incidence of childhood type 1 diabetes. Am J Clin Nutr. 2000;71:1525–9.
35. Muntoni S, Muntoni S., Epidemiological association between some dietary habits and the increasing incidence of type 1 diabetes worldwide. Ann Nutr Metab. 2006;50:11–9.
36. Savilahti E, Saarinen KM., Early infant feeding and type 1 diabetes. Europ J Nutr. 2009;48:243–9.
37. Ziegler AG, Schmid S, Huber D, Hummel M., Bonifacio E. Early infant feeding and risk of developing type 1 diabetes-associated autoantibodies. JAMA. 2003;290:1721–8.
38. Norris JM, Barriga K, Klingensmith G, Hoffman M, Eisenbarth GS, Erlich HA, et al. Timing of initial cereal exposure in infancy and risk of islet autoimmunity. JAMA. 2003;290:1713–20.
39. Hummel S, Pfluger M, Hummel M, Bonifacio E, Ziegler AG., Primary dietary intervention study to reduce the risk of islet autoimmunity in children at increased risk for type 1 diabetes:the BABYDIET study. Diabetes Care. 2011;34:1301–5.
40. Hummel S, Ziegler AG., Early determinants of type 1 diabetes:experience from the BABYDIAB and BABYDIET studies. Am J Clin Nutr. 2011;94:1821S–3S.
41. Funda DP, Kaas A, Bock T, Tlaskalova-Hogenova H, Buschard K., Gluten-free diet prevents diabetes in NOD mice. Diabetes/Metab Res Rev. 1999;15:323–7.
42. Marietta EV, Gomez AM, Yeoman C, Tilahun AY, Clark CR, Luckey DH, et al. Low incidence of spontaneous type 1 diabetes in non-obese diabetic mice raised on gluten-free diets is associated with changes in the intestinal microbiome. PLoS One. 2013;8:e78687.
43. Flohe SB, Wasmuth HE, Kerad JB, Beales PE, Pozzilli P, Elliott RB, et al. A wheat-based, diabetes-promoting diet induces a Th1-type cytokine bias in the gut of NOD mice. Cytokine. 2003;21:149–54.
44. Patrick C, Wang GS, Lefebvre DE, Crookshank JA, Sonier B, Eberhard C, et al. Promotion of autoimmune diabetes by cereal diet in the presence or absence of microbes associated with gut immune activation, regulatory imbalance, and altered cathelicidin antimicrobial Peptide. Diabetes. 2013;62:2036–47.
45. Kahaly GJ, Hansen MP., Type 1 diabetes associated autoimmunity. Autoimmun Rev. 2016;15:644–648.
46. Virtanen SM, Jaakkola L, Rasanen L, Ylonen K, Aro A, Lounamaa R, et al. Nitrate and nitrite intake and the risk for type 1 diabetes in Finnish children. Childhood Diabetes in Finland Study Group. Diabetic Med. 1994;11:656–62.
47. von Herrath MG, Fujinami RS, Whitton JL., Microorganisms and autoimmunity:making the barren field fertile? Nat Rev Microbiol. 2003;1:151–7.
48. Coppieters KT, Wiberg A, von Herrath MG., Viral infections and molecular mimicry in type 1 diabetes. APMIS. 2012;120:941–9.
49. Kondrashova A, Hyoty H., Role of viruses and other microbes in the pathogenesis of type 1 diabetes. Int Rev Immunol. 2014;33:284–95.
50. Gale EA., A missing link in the hygiene hypothesis? Diabetologia. 2002;45:588–94.
51. Saunders KA, Raine T, Cooke A, Lawrence CE., Inhibition of autoimmune type 1 diabetes by gastrointestinal helminth infection. Infect Immun. 2007;75:397–407.
52. Zaccone P, Cooke A., Vaccine against autoimmune disease:can helminths or their products provide a therapy? Curr Opin Immunol. 2013;25:418–23.
53. Hubner MP, Shi Y, Torrero MN, Mueller E, Larson D, Soloviova K, et al. Helminth protection against autoimmune diabetes in nonobese diabetic mice is independent of a type 2 immune shift and requires TGF-beta. J Immunol. 2012;188:559–68.
54. Viggiano D, Ianiro G, Vanella G, Bibbo S, Bruno G, Simeone G, et al. Gut barrier in health and disease:focus on childhood. Europ Rev Med Pharmacol Sci. 2015;19:1077–85.
55. Li X, Atkinson MA., The role for gut permeability in the pathogenesis of type 1 diabetes-a solid or leaky concept? Pediatr Diabetes. 2015;16:485–92.
56. Gomes AC, Bueno AA, de Souza RG, Mota JF., Gut microbiota, probiotics and diabetes. Nutr J. 2014;13:60.
57. Guilloteau P, Martin L, Eeckhaut V, Ducatelle R, Zabielski R, Van Immerseel F., From the gut to the peripheral tissues:the multiple effects of butyrate. Nutr Res Rev. 2010;23:366–84.
58. Flint HJ, Duncan SH, Scott KP, Louis P., Interactions and competition within the microbial community of the human colon:links between diet and health. Environ Microbiol. 2007;9:1101–11.
59. Brown CT, Davis-Richardson AG, Giongo A, Gano KA, Crabb DB, Mukherjee N, et al. Gut microbiome metagenomics analysis suggests a functional model for the development of autoimmunity for type 1 diabetes. PLoS One. 2011;6:e25792.
60. Mejia-Leon ME, Petrosino JF, Ajami NJ, Dominguez-Bello MG, de la Barca AM., Fecal microbiota imbalance in Mexican children with type 1 diabetes. Sci Rep. 2014;4:3814.
61. de Goffau MC, Fuentes S, van den Bogert B, Honkanen H, de Vos WM, Welling GW, et al. Aberrant gut microbiota composition at the onset of type 1 diabetes in young children. Diabetologia. 2014;57:1569–77.
62. Van den Abbeele P, Belzer C, Goossens M, Kleerebezem M, De Vos WM, Thas O, et al. Butyrate-producing Clostridium cluster XIVa species specifically colonize mucins in an in vitro gut model. ISME J. 2013;7:949–61.
63. Meddings JB, Jarand J, Urbanski SJ, Hardin J, Gall DG., Increased gastrointestinal permeability is an early lesion in the spontaneously diabetic BB rat. Am J Physiol. 1999;276:G951–7.
64. Graham S, Courtois P, Malaisse WJ, Rozing J, Scott FW, Mowat AM., Enteropathy precedes type 1 diabetes in the BB rat. Gut. 2004;53:1437–44.
65. Lee AS, Gibson DL, Zhang Y, Sham HP, Vallance BA, Dutz JP., Gut barrier disruption by an enteric bacterial pathogen accelerates insulitis in NOD mice. Diabetologia. 2010;53:741–8.
66. Neu J, Reverte CM, Mackey AD, Liboni K, Tuhacek-Tenace LM, Hatch M, et al. Changes in intestinal morphology and permeability in the biobreeding rat before the onset of type 1 diabetes. J Pediatr Gastroenterol Nutr. 2005;40:589–95.
67. Watts T, Berti I, Sapone A, Gerarduzzi T, Not T, Zielke R, et al. Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats. Proc Nat Acad Sci USA. 2005;102:2916–21.
68. Visser JT, Lammers K, Hoogendijk A, Boer MW, Brugman S, Beijer-Liefers S, et al. Restoration of impaired intestinal barrier function by the hydrolysed casein diet contributes to the prevention of type 1 diabetes in the diabetes-prone BioBreeding rat. Diabetologia. 2010;53:2621–8.
69. Bosi E, Molteni L, Radaelli MG, Folini L, Fermo I, Bazzigaluppi E, et al. Increased intestinal permeability precedes clinical onset of type 1 diabetes. Diabetologia. 2006;49:2824–7.
70. Secondulfo M, Iafusco D, Carratu R, deMagistris L, Sapone A, Generoso M, et al. Ultrastructural mucosal alterations and increased intestinal permeability in non-celiac, type I diabetic patients. Dig Liver Dis.2004;36:35–45.
71. Kuitunen M, Saukkonen T, Ilonen J, Akerblom HK, Savilahti E., Intestinal permeability to mannitol and lactulose in children with type 1 diabetes with the HLA-DQB1*02 allele. Autoimmunity. 2002;35:365–8.
72. Sapone A, de Magistris L, Pietzak M, Clemente MG, Tripathi A, Cucca F, et al. Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes. 2006;55:1443–9.
73. Mejia-Leon ME, Barca AM., Diet, Microbiota and Immune System in Type 1 Diabetes Development and Evolution. Nutrients. 2015;7:9171–84.
74. Gulden E, Wong FS, Wen L., The gut microbiota and Type 1 Diabetes. Clin Immunol.2015;159:143–53.
75. McLean MH, Dieguez D, Jr., Miller LM, Young HA., Does the microbiota play a role in the pathogenesis of autoimmune diseases? Gut. 2015;64:332–41.
76. Knip M, Siljander H., The role of the intestinal microbiota in type 1 diabetes mellitus. Nat Rev Endocrinol. 2016;12:154–67.
77. Borody TJ, Campbell J., Fecal microbiota transplantation:techniques, applications, and issues. Gastroenterol Clin North Am. 2012;41:781–803.
78. Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R., Diversity, stability and resilience of the human gut microbiota. Nature. 2012;489:220–30.
79. Shapiro H, Thaiss CA, Levy M, Elinav E., The cross talk between microbiota and the immune system:metabolites take center stage. Curr Opin Immunol. 2014;30:54–62.
80. Surana NK, Kasper DL., The yin yang of bacterial polysaccharides:lessons learned from B. fragilis PSA. Immunol Rev. 2012;245:13–26.
81. Hoorfar J, Buschard K, Dagnaes-Hansen F., Prophylactic nutritional modification of the incidence of diabetes in autoimmune non-obese diabetic (NOD) mice. Brit J Nutr. 1993;69:597–607.
82. Lau K, Benitez P, Ardissone A, Wilson TD, Collins EL, Lorca G, et al. Inhibition of type 1 diabetes correlated to a Lactobacillus johnsonii N6.2-mediated Th17 bias. J Immunol. 2011;186:3538–46.
83. Hara N, Alkanani AK, Ir D, Robertson CE, Wagner BD, Frank DN, et al. Prevention of virus-induced type 1 diabetes with antibiotic therapy. J Immunol. 2012;189:3805–14.
84. Roesch LF, Lorca GL, Casella G, Giongo A, Naranjo A, Pionzio AM, et al. Culture-independent identification of gut bacteria correlated with the onset of diabetes in a rat model. The ISME J. 2009;3:536–48.
85. Wolf KJ, Daft JG, Tanner SM, Hartmann R, Khafipour E, Lorenz RG., Consumption of acidic water alters the gut microbiome and decreases the risk of diabetes in NOD mice. J Histochem Cytochem.2014;62:237–50.
86. Toivonen RK, Emani R, Munukka E, Rintala A, Laiho A, Pietila S, et al. Fermentable fibres condition colon microbiota and promote diabetogenesis in NOD mice. Diabetologia. 2014;57:2183–92.
87. Hansen CH, Krych L, Nielsen DS, Vogensen FK, Hansen LH, Sorensen SJ, et al. Early life treatment with vancomycin propagates Akkermansia muciniphila and reduces diabetes incidence in the NOD mouse. Diabetologia. 2012;55:2285–94.
88. Kriegel MA, Sefik E, Hill JA, Wu HJ, Benoist C, Mathis D., Naturally transmitted segmented filamentous bacteria segregate with diabetes protection in nonobese diabetic mice. Proc Nat Acad Sci USA. 2011;108:11548–53.
89. Valladares R, Sankar D, Li N, Williams E, Lai KK, Abdelgeliel AS, et al. Lactobacillus johnsonii N6.2 mitigates the development of type 1 diabetes in BB-DP rats. PLoS One. 2010;5:e10507.
90. Krych L, Nielsen DS, Hansen AK, Hansen CH. Gut microbial markers are associated with diabetes onset, regulatory imbalance, and IFN-γ level in NOD mice. Gut Microbes. 2015;6:101–9.
91. Wirth R, Bodi N, Maroti G, Bagyanszki M, Talapka P, Fekete E, et al. Regionally distinct alterations in the composition of the gut microbiota in rats with streptozotocin-induced diabetes. PLoS One. 2014;9:e110440.
92. Wen L, Ley RE, Volchkov PY, Stranges PB, Avanesyan L, Stonebraker AC, et al. Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature. 2008;455:1109–13.
93. Thomas HE, McKenzie MD, Angstetra E, Campbell PD, Kay TW., Beta cell apoptosis in diabetes. Apoptosis. 2009;14:1389–404.
94. Tai N, Wong FS, Wen L., The role of gut microbiota in the development of type 1, type 2 diabetes mellitus and obesity. Rev Endocr Metab Disord. 2015;16:55–65.
95. Yang Y, Torchinsky MB, Gobert M, Xiong H, Xu M, Linehan JL, et al. Focused specificity of intestinal TH17 cells towards commensal bacterial antigens. Nature. 2014;510:152–6.
96. Geuking MB, McCoy KD, Macpherson AJ., The continuum of intestinal CD4+ T cell adaptations in host-microbial mutualism. Gut Microbes. 2011;2:353–7.
97. Ochoa-Reparaz J, Mielcarz DW, Haque-Begum S, Kasper LH., Induction of a regulatory B cell population in experimental allergic encephalomyelitis by alteration of the gut commensal microflora. Gut Microbes. 2010;1:103–8.
98. Murri M, Leiva I, Gomez-Zumaquero JM, Tinahones FJ, Cardona F, Soriguer F, et al. Gut microbiota in children with type 1 diabetes differs from that in healthy children:a case-control study. BMC Medicine. 2013;11:46.
99. Giongo A, Gano KA, Crabb DB, Mukherjee N, Novelo LL, Casella G, et al. Toward defining the autoimmune microbiome for type 1 diabetes. ISME J. 2011;5:82–91.
100. de Goffau MC, Luopajarvi K, Knip M, Ilonen J, Ruohtula T, Harkonen T, et al. Fecal microbiota composition differs between children with beta-cell autoimmunity and those without. Diabetes. 2013;62:1238–44.
101. Davis-Richardson AG, Ardissone AN, Dias R, Simell V, Leonard MT, Kemppainen KM, et al. Bacteroides dorei dominates gut microbiome prior to autoimmunity in Finnish children at high risk for type 1 diabetes. Front Microbiol. 2014;5:678.
102. Kostic AD, Gevers D, Siljander H, Vatanen T, Hyotylainen T, Hamalainen AM, et al. The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes. Cell Host Microbe. 2015;17:260–73.
103. Alkanani AK, Hara N, Gottlieb PA, Ir D, Robertson CE, Wagner BD, et al. Alterations in intestinal microbiota correlate with susceptibility to type 1 diabetes. Diabetes. 2015;64:3510–20.
104. Endesfelder D, zu Castell W, Ardissone A, Davis-Richardson AG, Achenbach P, Hagen M, et al. Compromised gut microbiota networks in children with anti-islet cell autoimmunity. Diabetes. 2014;63:2006–14.
105. Soyucen E, Gulcan A, Aktuglu-Zeybek AC, Onal H, Kiykim E, Aydin A., Differences in the gut microbiota of healthy children and those with type 1 diabetes. Pediatr Int.: 2014;56:336–43.
106. Kondrashova A, Seiskari T, Ilonen J, Knip M, Hyoty H., The ‘Hygiene hypothesis’ and the sharp gradient in the incidence of autoimmune and allergic diseases between Russian Karelia and Finland. APMIS. 2013;121:478–93.
107. Delitala AP, Pes GM, Malaty HM, Pisanu G, Delitala G, Dore MP., Implication of cytotoxic helicobacter pylori infection in autoimmune diabetes. J Diabetes Res. 2016:7347065.
108. Peng J, Narasimhan S, Marchesi JR, Benson A, Wong FS, Wen L., Long term effect of gut microbiota transfer on diabetes development. J Autoimmun. 2014;53:85–94.
109. Takiishi T, Korf H, Van Belle TL, Robert S, Grieco FA, Caluwaerts S, et al. Reversal of autoimmune diabetes by restoration of antigen-specific tolerance using genetically modified Lactococcus lactis in mice. J Clin Invest. 2012;122:1717–25.
110. Robert S, Gysemans C, Takiishi T, Korf H, Spagnuolo I, Sebastiani G, et al. Oral delivery of glutamic acid decarboxylase (GAD)-65 and IL10 by Lactococcus lactis reverses diabetes in recent-onset NOD mice. Diabetes. 2014;63:2876–87.
111. Markle JG, Frank DN, Mortin-Toth S, Robertson CE, Feazel LM, Rolle-Kampczyk U, et al. Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity. Science. 2013;339:1084–8.
112. Calcinaro F, Dionisi S, Marinaro M, Candeloro P, Bonato V, Marzotti S, et al. Oral probiotic administration induces interleukin-10 production and prevents spontaneous autoimmune diabetes in the non-obese diabetic mouse. Diabetologia. 2005;48:1565–75.
113. Dolpady J, Sorini C, Di Pietro C, Cosorich I, Ferrarese R, Saita D, et al. Oral Probiotic VSL#3 Prevents Autoimmune Diabetes by Modulating Microbiota and Promoting Indoleamine 2,3-Dioxygenase-Enriched Tolerogenic Intestinal Environment. J Diabetes Res. 2016;2016:7569431.