Where genes meet environment—integrating the role of gut luminal contents, immunity and pancreas in type 1 diabetes

Translational Research

Volumn 179, Issue , 2017, Pages 183-198

  Scott, Fraser W ^a,b   Pound, Lynley D ^a   Patrick, Christopher ^a   Eberhard, Chandra E ^a,b   Crookshank, Jennifer A ^a  

^a OTTAWA HOSPITAL RESEARCH INSTITUTE   (Canada)

^b UNIVERSITY OF OTTAWA   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBIOTIC AGENT; CATHELICIDIN; POLYPEPTIDE ANTIBIOTIC AGENT;

DIET; DYSBIOSIS; GENE; GENETIC RISK; GENOTYPE ENVIRONMENT INTERACTION; HUMAN; IMMUNITY; IMMUNOGENETICS; IMMUNOLOGICAL TOLERANCE; IMMUNOMODULATION; INFLAMMATION; INSULIN DEPENDENT DIABETES MELLITUS; INTESTINE FLORA; MACROPHAGE; NONHUMAN; PANCREAS; PANCREAS ISLET BETA CELL; PATHOGENESIS; PRIORITY JOURNAL; REVIEW; ANIMAL; BIOLOGICAL MODEL; GASTROINTESTINAL TRACT; GENETICS; METABOLISM; PATHOLOGY;

ANIMALS; DIABETES MELLITUS, TYPE 1; GASTROINTESTINAL TRACT; GENE-ENVIRONMENT INTERACTION; HUMANS; IMMUNITY; MODELS, BIOLOGICAL; PANCREAS;

EID: 85006001626     PISSN: 19315244     EISSN: 18781810     Source Type: Journal    
DOI: 10.1016/j.trsl.2016.09.001     Document Type: Review

References (151)

1. 1 Stene, L.C., Gaps in life expectancy for people with type 1 diabetes. Diabetologia 59 (2016), 1150–1152.
2. 2 Wentworth, J.M., Fourlanos, S., Harrison, L.C., Reappraising the stereotypes of diabetes in the modern diabetogenic environment. Nat Rev Endocrinol 5 (2009), 483–489.
3. 3 Lefebvre, D.E., Powell, K.L., Strom, A., Scott, F.W., Dietary proteins as environmental modifiers of type 1 diabetes mellitus. Annu Rev Nutr 26 (2006), 175–202.
4. 4 Atkinson, M.A., von Herrath, M., Powers, A.C., Clare-Salzler, M., Current concepts on the pathogenesis of type 1 diabetes–considerations for attempts to prevent and reverse the disease. Diabetes Care 38 (2015), 979–988.
5. 5 Pociot, F., Akolkar, B., Concannon, P., et al. Genetics of type 1 diabetes: what's next?. Diabetes 59 (2010), 1561–1571.
6. 6 Scalbert, A., Brennan, L., Manach, C., et al. The food metabolome: a window over dietary exposure. Am J Clin Nutr 99 (2014), 1286–1308.
7. 7 Kondrashova, A., Reunanen, A., Romanov, A., et al. A six-fold gradient in the incidence of type 1 diabetes at the eastern border of Finland. Ann Med 37 (2005), 67–72.
8. 8 Scott, F.W., Food-induced type 1 diabetes in the BB rat. Diabetes Metab Rev 12 (1996), 341–359.
9. 9 Scott, F.W., Cloutier, H.E., Kleemann, R., et al. Potential mechanisms by which certain foods promote or inhibit the development of spontaneous diabetes in BB rats: dose, timing, early effect on islet area, and switch in infiltrate from Th1 to Th2 cells. Diabetes 46 (1997), 589–598.
10. 10 Scott, F.W., Rowsell, P., Wang, G.S., Burghardt, K., Kolb, H., Flohe, S., Oral exposure to diabetes-promoting food or immunomodulators in neonates alters gut cytokines and diabetes. Diabetes 51 (2002), 73–78.
11. 11 Houston, S.A., Cerovic, V., Thomson, C., Brewer, J., Mowat, A.M., Milling, S., The lymph nodes draining the small intestine and colon are anatomically separate and immunologically distinct. Mucosal Immunol 9 (2016), 468–478.
12. 12 Patrick, C., Wang, G.S., Lefebvre, D.E., 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 62 (2013), 2036–2047.
13. 13 Husseini, M., Wang, G.S., Patrick, C., et al. Heme Oxygenase-1 induction prevents autoimmune diabetes in association with pancreatic recruitment of M2-like macrophages, mesenchymal cells, and fibrocytes. Endocrinology 156 (2015), 3937–3949.
14. 14 Pound, L.D., Patrick, C., Eberhard, C.E., et al. Cathelicidin antimicrobial peptide: a novel regulator of islet function, islet regeneration, and selected gut bacteria. Diabetes 64 (2015), 4135–4147.
15. 15 Wild, C.P., Complementing the genome with an “exposome”: the outstanding challenge of environmental exposure measurement in molecular epidemiology. Cancer Epidemiol Biomarkers Prev 14 (2005), 1847–1850.
16. 16 Wild, C.P., The exposome: from concept to utility. Int J Epidemiol 41 (2012), 24–32.
17. 17 Floyel, T., Kaur, S., Pociot, F., Genes affecting beta-cell function in type 1 diabetes. Curr Diab Rep, 15, 2015, 97.
18. 18 Onengut-Gumuscu, S., Chen, W.M., Burren, O., et al. Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers. Nat Genet 47 (2015), 381–386.
19. 19 Bergholdt, R., Brorsson, C., Palleja, A., et al. Identification of novel type 1 diabetes candidate genes by integrating genome-wide association data, protein-protein interactions, and human pancreatic islet gene expression. Diabetes 61 (2012), 954–962.
20. 20 Eizirik, D.L., Sammeth, M., Bouckenooghe, T., et al. The human pancreatic islet transcriptome: expression of candidate genes for type 1 diabetes and the impact of pro-inflammatory cytokines. PLoS Genet, 8, 2012, e1002552.
21. 21 Lysy, P.A., Weir, G.C., Bonner-Weir, S., Concise review: pancreas regeneration: recent advances and perspectives. Stem Cells Transl Med 1 (2012), 150–159.
22. 22 Kaddis, J.S., Pugliese, A., Atkinson, M.A., A run on the biobank: what have we learned about type 1 diabetes from the nPOD tissue repository?. Curr Opin Endocrinol Diabetes Obes 22 (2015), 290–295.
23. 23 Leete, P., Willcox, A., Krogvold, L., et al. Differential insulitic profiles determine the extent of beta cell destruction and the age at onset of type 1 diabetes. Diabetes 65 (2016), 1362–1369.
24. 24 Campbell-Thompson, M.L., Atkinson, M.A., Butler, A.E., et al. The diagnosis of insulitis in human type 1 diabetes. Diabetologia 56 (2013), 2541–2543.
25. 25 Campbell-Thompson, M., Fu, A., Kaddis, J.S., et al. Insulitis and beta-cell mass in the natural history of type 1 diabetes. Diabetes 65 (2016), 719–731.
26. 26 Campbell-Thompson, M., Wasserfall, C., Montgomery, E.L., Atkinson, M.A., Kaddis, J.S., Pancreas organ weight in individuals with disease-associated autoantibodies at risk for type 1 diabetes. JAMA 308 (2012), 2337–2339.
27. 27 Foulis, A.K., Stewart, J.A., The pancreas in recent-onset type 1 (insulin-dependent) diabetes mellitus: insulin content of islets, insulitis and associated changes in the exocrine acinar tissue. Diabetologia 26 (1984), 456–461.
28. 28 Gepts, W., Pathologic anatomy of the pancreas in juvenile diabetes mellitus. Diabetes 14 (1965), 619–633.
29. 29 Rodriguez-Calvo, T., Ekwall, O., Amirian, N., Zapardiel-Gonzalo, J., von Herrath, M.G., Increased immune cell infiltration of the exocrine pancreas: a possible contribution to the pathogenesis of type 1 diabetes. Diabetes 63 (2014), 3880–3890.
30. 30 Koskinen, M.K., Helminen, O., Matomaki, J., et al. Reduced beta-cell function in early preclinical type 1 diabetes. Eur J Endocrinol 174 (2016), 251–259.
31. 31 Brorsson, C.A., Onengut, S., Chen, W.M., et al. Novel association between immune-mediated susceptibility loci and persistent autoantibody positivity in type 1 diabetes. Diabetes 64 (2015), 3017–3027.
32. 32 Frederiksen, B.N., Steck, A.K., Kroehl, M., et al. Evidence of stage- and age-related heterogeneity of non-HLA SNPs and risk of islet autoimmunity and type 1 diabetes: the diabetes autoimmunity study in the young. Clin Dev Immunol, 2013, 2013, 417657.
33. 33 Keenan, H.A., Sun, J.K., Levine, J., et al. Residual insulin production and pancreatic ss-cell turnover after 50 years of diabetes: Joslin Medalist Study. Diabetes 59 (2011), 2846–2853.
34. 34 Kauri, L.M., Wang, G.S., Patrick, C., Bareggi, M., Hill, D.J., Scott, F.W., Increased islet neogenesis without increased islet mass precedes autoimmune attack in diabetes-prone rats. Lab Invest 87 (2007), 1240–1251.
35. 35 Wang, G.S., Karamchandani, J., Pulido, O., Rosenberg, L., Scott, F.W., Altered islet homeostasis before classic insulitis in BB rats. Diabetes Metab, 28, 2002 3S90–3S97.
36. 36 Wang, G.S., Rosenberg, L., Scott, F.W., Tubular complexes as a source for islet neogenesis in the pancreas of diabetes-prone BB rats. Lab Invest 85 (2005), 675–688.
37. 37 Seemayer, T.A., Colle, E., Tannenbaum, G.S., Oligny, L.L., Guttmann, R.D., Goldman, H., Spontaneous diabetes mellitus syndrome in the rat. III. Pancreatic alterations in aglycosuric and untreated diabetic BB Wistar-derived rats. Metabolism 32 (1983), 26–32.
38. 38 Hattori, M., Fukuda, M., Ichikawa, T., Baumgartl, H.J., Katoh, H., Makino, S., A single recessive non-MHC diabetogenic gene determines the development of insulitis in the presence of an MHC-linked diabetogenic gene in NOD mice. J Autoimmun 3 (1990), 1–10.
39. 39 Parsa, R., Andresen, P., Gillett, A., et al. Adoptive transfer of immunomodulatory M2 macrophages prevents type 1 diabetes in NOD mice. Diabetes 61 (2012), 2881–2892.
40. 40 Herold, K.C., Vignali, D.A., Cooke, A., Bluestone, J.A., Type 1 diabetes: translating mechanistic observations into effective clinical outcomes. Nat Rev Immunol 13 (2013), 243–256.
41. 41 Morgan, N.G., Leete, P., Foulis, A.K., Richardson, S.J., Islet inflammation in human type 1 diabetes mellitus. IUBMB Life 66 (2015), 723–734.
42. 42 Vegas, A.J., Veiseh, O., Gurtler, M., et al. Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice. Nat Med 22 (2016), 306–311.
43. 43 Keeney, K.M., Yurist-Doutsch, S., Arrieta, M.C., Finlay, B.B., Effects of antibiotics on human microbiota and subsequent disease. Annu Rev Microbiol 68 (2014), 217–235.
44. 44 Dunne, J.L., Triplett, E.W., Gevers, D., et al. The intestinal microbiome in type 1 diabetes. Clin Exp Immunol 177 (2014), 30–37.
45. 45 Hu, C., Wong, F.S., Wen, L., Type 1 diabetes and gut microbiota: Friend or foe?. Pharmacol Res 98 (2015), 9–15.
46. 46 McLean, M.H., Dieguez, D. Jr., Miller, L.M., Young, H.A., Does the microbiota play a role in the pathogenesis of autoimmune diseases?. Gut 64 (2015), 332–341.
47. 47 Neu, J., Lorca, G., Kingma, S.D., Triplett, E.W., The intestinal microbiome: relationship to type 1 diabetes. Endocrinol Metab Clin North Am 39 (2010), 563–571.
48. 48 Nielsen, D.S., Krych, L., Buschard, K., Hansen, C.H., Hansen, A.K., Beyond genetics. Influence of dietary factors and gut microbiota on type 1 diabetes. FEBS Lett 588 (2014), 4234–4243.
49. 49 Paun, A., Danska, J.S., Immuno-ecology: how the microbiome regulates tolerance and autoimmunity. Curr Opin Immunol 37 (2015), 34–39.
50. 50 Giongo, A., Gano, K.A., Crabb, D.B., et al. Toward defining the autoimmune microbiome for type 1 diabetes. ISME J 5 (2011), 82–91.
51. 51 Knip, M., Siljander, H., The role of the intestinal microbiota in type 1 diabetes mellitus. Nat Rev Endocrinol 12 (2016), 154–167.
52. 52 Tai, N., Wong, F.S., Wen, L., The role of gut microbiota in the development of type 1, type 2 diabetes mellitus and obesity. Rev Endocr Metab Disord 16 (2015), 55–65.
53. 53 Daft, J.G., Lorenz, R.G., Role of the gastrointestinal ecosystem in the development of type 1 diabetes. Pediatr Diabetes 16 (2015), 407–418.
54. 54 Gulden, E., Wong, F.S., Wen, L., The gut microbiota and Type 1 Diabetes. Clin Immunol 159 (2015), 143–153.
55. 55 Mejia-Leon, M.E., Barca, A.M., Diet, microbiota and immune system in type 1 diabetes development and Evolution. Nutrients 7 (2015), 9171–9184.
56. 56 Ji, B., Nielsen, J., From next-generation sequencing to systematic modeling of the gut microbiome. Front Genet, 6, 2015, 219.
57. 57 Roesch, L.F., Lorca, G.L., Casella, G., et al. Culture-independent identification of gut bacteria correlated with the onset of diabetes in a rat model. ISME J 3 (2009), 536–548.
58. 58 Brugman, S., Klatter, F.A., Visser, J.T., et al. Antibiotic treatment partially protects against type 1 diabetes in the Bio-Breeding diabetes-prone rat. Is the gut flora involved in the development of type 1 diabetes?. Diabetologia 49 (2006), 2105–2108.
59. 59 Markle, J.G., Frank, D.N., Mortin-Toth, S., et al. Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity. Science 339 (2013), 1084–1088.
60. 60 Wen, L., Ley, R.E., Volchkov, P.Y., et al. Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature 455 (2008), 1109–1113.
61. 61 Yurkovetskiy, L., Burrows, M., Khan, A.A., et al. Gender bias in autoimmunity is influenced by microbiota. Immunity 39 (2013), 400–412.
62. 62 Alam, C., Bittoun, E., Bhagwat, D., et al. Effects of a germ-free environment on gut immune regulation and diabetes progression in non-obese diabetic (NOD) mice. Diabetologia 54 (2011), 1398–1406.
63. 63 King, C., Sarvetnick, N., The incidence of type-1 diabetes in NOD mice is modulated by restricted flora not germ-free conditions. PLoS One, 6, 2011, e17049.
64. 64 Kugelberg, E., Mucosal immunology: bacteria get T(Reg) cells into shape. Nat Rev Immunol 14 (2014), 2–3.
65. 65 Kostic, A.D., Gevers, D., Siljander, H., et al. The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes. Cell Host Microbe 17 (2015), 260–273.
66. 66 Auricchio, R., Paparo, F., Maglio, M., et al. In vitro-deranged intestinal immune response to gliadin in type 1 diabetes. Diabetes 53 (2004), 1680–1683.
67. 67 Sapone, A., de Magistris, L., Pietzak, M., et al. Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes 55 (2006), 1443–1449.
68. 68 Secondulfo, M., Iafusco, D., Carratu, R., et al. Ultrastructural mucosal alterations and increased intestinal permeability in non-celiac, type I diabetic patients. Dig Liver Dis 36 (2004), 35–45.
69. 69 Westerholm-Ormio, M., Vaarala, O., Pihkala, P., Ilonen, J., Savilahti, E., Immunologic activity in the small intestinal mucosa of pediatric patients with type 1 diabetes. Diabetes 52 (2003), 2287–2295.
70. 70 Benson, A.K., Kelly, S.A., Legge, R., et al. Individuality in gut microbiota composition is a complex polygenic trait shaped by multiple environmental and host genetic factors. Proc Natl Acad Sci U S A 107 (2010), 18933–18938.
71. 71 Carmody, R.N., Gerber, G.K., Luevano, J.M. Jr., et al. Diet dominates host genotype in shaping the murine gut microbiota. Cell Host Microbe 17 (2015), 72–84.
72. 72 Org, E., Parks, B.W., Joo, J.W., et al. Genetic and environmental control of host-gut microbiota interactions. Genome Res 25 (2015), 1558–1569.
73. 73 Snell-Bergeon, J.K., Smith, J., Dong, F., et al. Early childhood infections and the risk of islet autoimmunity: the diabetes autoimmunity study in the young (DAISY). Diabetes Care 35 (2012), 2553–2558.
74. 74 Yurkovetskiy, L.A., Pickard, J.M., Chervonsky, A.V., Microbiota and autoimmunity: exploring new avenues. Cell Host Microbe 17 (2015), 548–552.
75. 75 Hummel, S., Pfluger, M., Hummel, M., Bonifacio, E., Ziegler, A.G., 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 34 (2011), 1301–1305.
76. 76 Endesfelder, D., zu Castell, W., Ardissone, A., et al. Compromised gut microbiota networks in children with anti-islet cell autoimmunity. Diabetes 63 (2014), 2006–2014.
77. 77 Tormo-Badia, N., Hakansson, A., Vasudevan, K., Molin, G., Ahrne, S., Cilio, C.M., Antibiotic treatment of pregnant non-obese diabetic mice leads to altered gut microbiota and intestinal immunological changes in the offspring. Scand J Immunol 80 (2014), 250–260.
78. 78 Hansen, C.H., Krych, L., Nielsen, D.S., et al. Early life treatment with vancomycin propagates Akkermansia muciniphila and reduces diabetes incidence in the NOD mouse. Diabetologia 55 (2012), 2285–2294.
79. 79 Brown, K., Godovannyi, A., Ma, C., et al. Prolonged antibiotic treatment induces a diabetogenic intestinal microbiome that accelerates diabetes in NOD mice. ISME J 10 (2015), 321–332.
80. 80 Hara, N., Alkanani, A.K., Ir, D., et al. Prevention of virus-induced type 1 diabetes with antibiotic therapy. J Immunol 189 (2012), 3805–3814.
81. 81 Rossini, A.A., Williams, R.M., Mordes, J.P., Appel, M.C., Like, A.A., Spontaneous diabetes in the gnotobiotic BB/W rat. Diabetes 28 (1979), 1031–1032.
82. 82 Funda D, Fundova P, Harrison LC. Microflora-dependency of selective diabetes-preventive diets: germ-free and ex-germ-free monocolonized NOD mice as models for studying environmental factors in type 1 diabetes. Proc 13th Int Congress Immunology MS-114 16 2007.
83. 83 EURODIAB. Infections and vaccinations as risk factors for childhood type I (insulin-dependent) diabetes mellitus: a multicentre case-control investigation. EURODIAB Substudy 2 Study Group. Diabetologia 43 (2000), 47–53.
84. 84 Cardwell, C.R., Carson, D.J., Patterson, C.C., No association between routinely recorded infections in early life and subsequent risk of childhood-onset Type 1 diabetes: a matched case-control study using the UK General Practice Research Database. Diabet Med 25 (2008), 261–267.
85. 85 Hviid, A., Svanstrom, H., Antibiotic use and type 1 diabetes in childhood. Am J Epidemiol 169 (2009), 1079–1084.
86. 86 Abela, A.G., Fava, S., Association of incidence of type 1 diabetes with mortality from infectious disease and with antibiotic susceptibility at a country level. Acta Diabetol 50 (2013), 859–865.
87. 87 Boursi, B., Mamtani, R., Haynes, K., Yang, Y.X., The effect of past antibiotic exposure on diabetes risk. Eur J Endocrinol 172 (2015), 639–648.
88. 88 Uusitalo, U., Liu, X., Yang, J., et al. Association of early exposure of probiotics and islet autoimmunity in the TEDDY study. JAMA Pediatr 170 (2016), 20–28.
89. 89 Fazeli Farsani, S., Souverein, P.C., van der Vorst, M.M., Knibbe, C.A., de Boer, A., Mantel-Teeuwisse, A.K., Population-based cohort study of anti-infective medication use before and after the onset of type 1 diabetes in children and adolescents. Antimicrob Agents Chemother 58 (2014), 4666–4674.
90. 90 Muegge, B.D., Kuczynski, J., Knights, D., et al. Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans. Science 332 (2011), 970–974.
91. 91 Walter, J., Murine gut microbiota-diet trumps genes. Cell Host Microbe 17 (2015), 3–5.
92. 92 Yatsunenko, T., Rey, F.E., Manary, M.J., et al. Human gut microbiome viewed across age and geography. Nature 486 (2012), 222–227.
93. 93 Kemppainen, K.M., Ardissone, A.N., Davis-Richardson, A.G., et al. Early childhood gut microbiomes show strong geographic differences among subjects at high risk for type 1 diabetes. Diabetes Care 38 (2015), 329–332.
94. 94 Mojibian, M., Chakir, H., Lefebvre, D.E., et al. A diabetes-specific HLA-DR restricted pro-inflammatory T cell response to wheat polypeptides in tissue transglutaminase antibody negative patients with type 1 diabetes. Diabetes 58 (2009), 1789–1796.
95. 95 Alam, C., Valkonen, S., Palagani, V., Jalava, J., Eerola, E., Hanninen, A., Inflammatory tendencies and overproduction of IL-17 in the colon of young NOD mice are counteracted with diet change. Diabetes 59 (2010), 2237–2246.
96. 96 Courtois, P., Nsimba, G., Jijakli, H., Sener, A., Scott, F.W., Malaisse, W.J., Gut permeability and intestinal mucins, invertase, and peroxidase in control and diabetes-prone BB rats fed either a protective or a diabetogenic diet. Dig Dis Sci 50 (2005), 266–275.
97. 97 Watts, T., Berti, I., Sapone, A., et al. Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats. Proc Natl Acad Sci U S A 102 (2005), 2916–2921.
98. 98 Courtois, P., Jurysta, C., Sener, A., Scott, F.W., Malaisse, W.J., Quantitative and qualitative alterations of intestinal mucins in BioBreeding rats. Int J Mol Med 15 (2005), 105–108.
99. 99 Emani, R., Alam, C., Pekkala, S., Zafar, S., Emani, M.R., Hanninen, A., Peritoneal cavity is a route for gut-derived microbial signals to promote autoimmunity in non-obese diabetic mice. Scand J Immunol 81 (2015), 102–109.
100. 100 Visser, J.T., Lammers, K., Hoogendijk, A., 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 53 (2010), 2621–2628.
101. 101 Beyan, H., Wen, L., Leslie, R.D., Guts, germs, and meals: the origin of type 1 diabetes. Curr Diab Rep 12 (2012), 456–462.
102. 102 Gale, E.A., The rise of childhood type 1 diabetes in the 20th century. Diabetes 51 (2002), 3353–3361.
103. 103 Knip, M., Akerblom, H.K., Becker, D., et al. Hydrolyzed infant formula and early beta-cell autoimmunity: a randomized clinical trial. JAMA 311 (2015), 2279–2287.
104. 104 Knip, M., Virtanen, S.M., Seppa, K., et al. Dietary intervention in infancy and later signs of beta-cell autoimmunity. N Engl J Med 363 (2010), 1900–1908.
105. 105 Ziegler, A.G., Nepom, G.T., Prediction and pathogenesis in type 1 diabetes. Immunity 32 (2010), 468–478.
106. 106 Caicedo, R.A., Li, N., Des Robert, C., et al. Neonatal formula feeding leads to immunological alterations in an animal model of type 1 diabetes. Pediatr Res 63 (2008), 303–307.
107. 107 Frederiksen, B.N., Kroehl, M., Baron, A., et al. Assessing age-related etiologic heterogeneity in the onset of islet autoimmunity. Biomed Res Int, 2015, 2015, 708289.
108. 108 Ray, K., Going against the grain. Nat Rev Gastroenterol Hepatol, 12, 2015, 547.
109. 109 Scott, F.W., Sarwar, G., Cloutier, H.E., Diabetogenicity of various protein sources in the diet of the diabetes-prone BB rat. Adv Exp Med Biol 246 (1988), 277–285.
110. 110 Funda, D.P., Kaas, A., Bock, T., Tlaskalova-Hogenova, H., Buschard, K., Gluten-free diet prevents diabetes in NOD mice. Diabetes Metab Res Rev 15 (1999), 323–327.
111. 111 Barbeau, W.E., What is the key environmental trigger in type 1 diabetes–is it viruses, or wheat gluten, or both?. Autoimmun Rev 12 (2012), 295–299.
112. 112 Barbeau, W.E., Hontecillas, R., Horne, W., Carbo, A., Koch, M.H., Bassaganya-Riera, J., Elevated CD8 T cell responses in type 1 diabetes patients to a 13 amino acid coeliac-active peptide from alpha-gliadin. Clin Exp Immunol 175 (2014), 167–171.
113. 113 Norris, J.M., Barriga, K., Klingensmith, G., et al. Timing of initial cereal exposure in infancy and risk of islet autoimmunity. JAMA 290 (2003), 1713–1720.
114. 114 Sildorf, S.M., Fredheim, S., Svensson, J., Buschard, K., Remission without insulin therapy on gluten-free diet in a 6-year old boy with type 1 diabetes mellitus. BMJ Case Rep, 2012, 2012, 10.1136/bcr.1102.2012.5878.
115. 115 Ziegler, A.G., Schmid, S., Huber, D., Hummel, M., Bonifacio, E., Early infant feeding and risk of developing type 1 diabetes-associated autoantibodies. JAMA 290 (2003), 1721–1728.
116. 116 Svensson, J., Sildorf, S.M., Pipper, C.B., et al. Potential beneficial effects of a gluten-free diet in newly diagnosed children with type 1 diabetes: a pilot study. Springerplus, 5, 2016, 994.
117. 117 Hamari, S., Kirveskoski, T., Glumoff, V., et al. CD4(+) T-cell proliferation responses to wheat polypeptide stimulation in children at different stages of type 1 diabetes autoimmunity. Pediatr Diabetes 16 (2015), 177–188.
118. 118 Catassi, C., Guerrieri, A., Bartolotta, E., Coppa, G.V., Giorgi, P.L., Antigliadin antibodies at onset of diabetes in children. Lancet, 2, 1987, 158.
119. 119 Chmiel, R., Beyerlein, A., Knopff, A., Hummel, S., Ziegler, A.G., Winkler, C., Early infant feeding and risk of developing islet autoimmunity and type 1 diabetes. Acta Diabetol 52 (2015), 621–624.
120. 120 Funda, D.P., Fundova, P., Hansen, A.K., Buschard, K., Prevention or early cure of type 1 diabetes by intranasal administration of gliadin in NOD mice. PLoS One, 9, 2014, e94530.
121. 121 Pabst, O., Mowat, A.M., Oral tolerance to food protein. Mucosal Immunol 5 (2012), 232–239.
122. 122 Hanenberg, H., Kolb-Bachofen, V., Kantwerk-Funke, G., Kolb, H., Macrophage infiltration precedes and is a prerequisite for lymphocytic insulitis in pancreatic islets of pre-diabetic BB rats. Diabetologia 32 (1989), 126–134.
123. 123 Ihm, S.H., Yoon, J.W., Studies on autoimmunity for initiation of beta-cell destruction. VI. Macrophages essential for development of beta-cell-specific cytotoxic effectors and insulitis in NOD mice. Diabetes 39 (1990), 1273–1278.
124. 124 Jorns, A., Gunther, A., Hedrich, H.J., Wedekind, D., Tiedge, M., Lenzen, S., Immune cell infiltration, cytokine expression, and beta-cell apoptosis during the development of type 1 diabetes in the spontaneously diabetic LEW.1AR1/Ztm-iddm rat. Diabetes 54 (2005), 2041–2052.
125. 125 Jun, H.S., Yoon, C.S., Zbytnuik, L., van Rooijen, N., Yoon, J.W., The role of macrophages in T cell-mediated autoimmune diabetes in nonobese diabetic mice. J Exp Med 189 (1999), 347–358.
126. 126 Kolb-Bachofen, V., Schraermeyer, U., Hoppe, T., Hanenberg, H., Kolb, H., Diabetes manifestation in BB rats is preceded by pan-pancreatic presence of activated inflammatory macrophages. Pancreas 7 (1992), 578–584.
127. 127 Cabrera, S.M., Chen, Y.G., Hagopian, W.A., Hessner, M.J., Blood-based signatures in type 1 diabetes. Diabetologia 59 (2016), 414–425.
128. 128 Cabrera, S.M., Henschel, A.M., Hessner, M.J., Innate inflammation in type 1 diabetes. Transl Res 167 (2016), 214–227.
129. 129 Mantovani, A., Sica, A., Sozzani, S., Allavena, P., Vecchi, A., Locati, M., The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 25 (2004), 677–686.
130. 130 Sica, A., Mantovani, A., Macrophage plasticity and polarization: in vivo veritas. J Clin Invest 122 (2012), 787–795.
131. 131 Martinez, F.O., Helming, L., Gordon, S., Alternative activation of macrophages: an immunologic functional perspective. Annu Rev Immunol 27 (2009), 451–483.
132. 132 Scaglia, L., Cahill, C.J., Finegood, D.T., Bonner-Weir, S., Apoptosis participates in the remodeling of the endocrine pancreas in the neonatal rat. Endocrinology 138 (1997), 1736–1741.
133. 133 Stoffels, K., Overbergh, L., Giulietti, A., et al. NOD macrophages produce high levels of inflammatory cytokines upon encounter of apoptotic or necrotic cells. J Autoimmun 23 (2004), 9–15.
134. 134 O'Brien, B.A., Fieldus, W.E., Field, C.J., Finegood, D.T., Clearance of apoptotic beta-cells is reduced in neonatal autoimmune diabetes-prone rats. Cell Death Differ 9 (2002), 457–464.
135. 135 Devaraj, S., Glaser, N., Griffen, S., Wang-Polagruto, J., Miguelino, E., Jialal, I., Increased monocytic activity and biomarkers of inflammation in patients with type 1 diabetes. Diabetes 55 (2006), 774–779.
136. 136 Calderon, B., Suri, A., Pan, X.O., Mills, J.C., Unanue, E.R., IFN-gamma-dependent regulatory circuits in immune inflammation highlighted in diabetes. J Immunol 181 (2008), 6964–6974.
137. 137 Thayer, T.C., Delano, M., Liu, C., et al. Superoxide production by macrophages and T cells is critical for the induction of autoreactivity and type 1 diabetes. Diabetes 60 (2011), 2144–2151.
138. 138 Valle, A., Giamporcaro, G.M., Scavini, M., et al. Reduction of circulating neutrophils precedes and accompanies type 1 diabetes. Diabetes 62 (2013), 2072–2077.
139. 139 Sun, J., Xu, M., Ortsater, H., et al. Cathelicidins positively regulate pancreatic beta-cell functions. FASEB J 30 (2016), 884–894.
140. 140 Sun, J., Furio, L., Mecheri, R., et al. Pancreatic beta-cells limit autoimmune diabetes via an immunoregulatory antimicrobial peptide expressed under the influence of the gut microbiota. Immunity 43 (2015), 304–317.
141. 141 Shaykhiev, R., Beisswenger, C., Kandler, K., et al. Human endogenous antibiotic LL-37 stimulates airway epithelial cell proliferation and wound closure. Am J Physiol Lung Cell Mol Physiol 289 (2005), L842–L848.
142. 142 Mathews, C.E., Utility of murine models for the study of spontaneous autoimmune type 1 diabetes. Pediatr Diabetes 6 (2005), 165–177.
143. 143 Jorns, A., Arndt, T., Meyer zu Vilsendorf, A., et al. Islet infiltration, cytokine expression and beta cell death in the NOD mouse, BB rat, Komeda rat, LEW.1AR1-iddm rat and humans with type 1 diabetes. Diabetologia 57 (2014), 512–521.
144. 144 Cardozo, A.K., Proost, P., Gysemans, C., Chen, M.C., Mathieu, C., Eizirik, D.L., IL-1beta and IFN-gamma induce the expression of diverse chemokines and IL-15 in human and rat pancreatic islet cells, and in islets from pre-diabetic NOD mice. Diabetologia 46 (2003), 255–266.
145. 145 Nica, A.C., Ongen, H., Irminger, J.C., et al. Cell-type, allelic, and genetic signatures in the human pancreatic beta cell transcriptome. Genome Res 23 (2013), 1554–1562.
146. 146 Marinkovic, T., Oresic, M., Modeling strategies to study metabolic pathways in progression to type 1 diabetes–Challenges and opportunities. Arch Biochem Biophys 589 (2015), 131–137.
147. 147 Zeevi, D., Korem, T., Zmora, N., et al. Personalized nutrition by prediction of glycemic responses. Cell 163 (2015), 1079–1094.
148. 148 Sonnenburg, E.D., Sonnenburg, J.L., Nutrition: a personal forecast. Nature 528 (2015), 484–486.
149. 149 Kaldunski, M., Jia, S., Geoffrey, R., et al. Identification of a serum-induced transcriptional signature associated with type 1 diabetes in the BioBreeding rat. Diabetes 59 (2010), 2375–2385.
150. 150 Chen, Y.G., Cabrera, S.M., Jia, S., et al. Molecular signatures differentiate immune states in type 1 diabetic families. Diabetes 63 (2014), 3960–3973.
151. 151 Cabrera, S.M., Wang, X., Chen, Y.G., et al. Interleukin-1 antagonism moderates the inflammatory state associated with Type 1 diabetes during clinical trials conducted at disease onset. Eur J Immunol 46 (2016), 1030–1046.