{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:03:17Z","timestamp":1790834597507,"version":"4.1.0"},"reference-count":121,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T00:00:00Z","timestamp":1615248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006595","name":"Unitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii","doi-asserted-by":"publisher","award":["224\/2021"],"award-info":[{"award-number":["224\/2021"]}],"id":[{"id":"10.13039\/501100006595","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Globally, we are facing a worrying increase in type 1 diabetes mellitus (T1DM) incidence, with onset at younger age shedding light on the need to better understand the mechanisms of disease and step-up prevention. Given its implication in immune system development and regulation of metabolism, there is no surprise that the gut microbiota is a possible culprit behind T1DM pathogenesis. Additionally, microbiota manipulation by probiotics, prebiotics, dietary factors and microbiota transplantation can all modulate early host\u2013microbiota interactions by enabling beneficial microbes with protective potential for individuals with T1DM or at high risk of developing T1DM. In this review, we discuss the challenges and perspectives of translating microbiome data into clinical practice. Nevertheless, this progress will only be possible if we focus our interest on developing numerous longitudinal, multicenter, interventional and double-blind randomized clinical trials to confirm their efficacy and safety of these therapeutic approaches.<\/jats:p>","DOI":"10.3390\/ijms22052763","type":"journal-article","created":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T06:22:32Z","timestamp":1615270952000},"page":"2763","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Dysbiosis in the Development of Type I Diabetes and Associated Complications: From Mechanisms to Targeted Gut Microbes Manipulation Therapies"],"prefix":"10.3390","volume":"22","author":[{"given":"Gratiela","family":"Gradisteanu Pircalabioru","sequence":"first","affiliation":[{"name":"Research Institute of University of Bucharest (ICUB), 300645 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3011-3108","authenticated-orcid":false,"given":"Nicolae","family":"Corcionivoschi","sequence":"additional","affiliation":[{"name":"Bacteriology Branch, Veterinary Sciences Division, Agri-Food and Biosciences Institute, Belfast BT9 5PX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3550-0545","authenticated-orcid":false,"given":"Ozan","family":"Gundogdu","sequence":"additional","affiliation":[{"name":"Faculty of Infectious &amp; Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6098-1857","authenticated-orcid":false,"given":"Mariana-Carmen","family":"Chifiriuc","sequence":"additional","affiliation":[{"name":"Research Institute of University of Bucharest (ICUB), 300645 Bucharest, Romania"},{"name":"Academy of Romanian Scientists, 050045 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luminita Gabriela","family":"Marutescu","sequence":"additional","affiliation":[{"name":"Research Institute of University of Bucharest (ICUB), 300645 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogdan","family":"Ispas","sequence":"additional","affiliation":[{"name":"Research Institute of University of Bucharest (ICUB), 300645 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5674-3810","authenticated-orcid":false,"given":"Octavian","family":"Savu","sequence":"additional","affiliation":[{"name":"\u201cN.C. Paulescu\u201d National Institute of Diabetes, Nutrition and Metabolic Diseases, 2nd District, 020042 Bucharest, Romania"},{"name":"Department of Doctoral School, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 5th District, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1542\/peds.2005-2824","article-title":"Factors influencing the composition of the intestinal microbiota in early infancy","volume":"118","author":"Penders","year":"2006","journal-title":"Pediatrics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3389\/fnut.2019.00021","article-title":"Gut microbiota, host organism, and diet trialogue in diabetes and obesity","volume":"6","author":"Lazar","year":"2019","journal-title":"Front. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.cell.2016.04.007","article-title":"Variation in microbiome lps immunogenicity contributes to autoimmunity in humans","volume":"165","author":"Vatanen","year":"2016","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.diabres.2013.11.005","article-title":"Diabetes in the young\u2014A global view and worldwide estimates of numbers of children with type 1 diabetes","volume":"103","author":"Patterson","year":"2014","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1097\/MED.0000000000000483","article-title":"The gut microbiota in type 1 diabetes","volume":"26","author":"Gavin","year":"2019","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_6","unstructured":"American-Diabetes-Association (2020). Standards of medical care in diabetes. Diabetes Care, 43, S1\u2013S207."},{"key":"ref_7","unstructured":"Department of Health and Human Services: Centers for Disease Control and Prevention (2011). Ndfs_2011, National Diabetes Fact Sheet: National Estimates General Information Diabetes Prediabetes USA."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1111\/j.1464-5491.2011.03288.x","article-title":"Trends in type 1 diabetes incidence in the UK in 0- to 14-year-olds and in 15- to 34-year-olds, 1991\u20132008","volume":"28","author":"Imkampe","year":"2011","journal-title":"Diabet. Med."},{"key":"ref_9","first-page":"1","article-title":"Global epidemiology of type 1 diabetes in young adults and adults: A systematic review","volume":"15","author":"Valleron","year":"2015","journal-title":"BMC Public Health"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/pedi.12773","article-title":"ISPAD clinical practice consensus guidelines 2018: Definition, epidemiology, and classification of diabetes in children and adolescents","volume":"19","author":"Kahkoska","year":"2018","journal-title":"Pediatr. Diabetes"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"nrdp201716","DOI":"10.1038\/nrdp.2017.16","article-title":"Type 1 diabetes mellitus","volume":"3","author":"Katsarou","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1007\/s11892-013-0433-5","article-title":"The emerging global epidemic of type 1 diabetes","volume":"13","author":"Tuomilehto","year":"2013","journal-title":"Curr. Diabetes Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1159\/000329169","article-title":"Pathogenesis of type 1 diabetes: Implications for incidence trends","volume":"76","author":"Knip","year":"2011","journal-title":"Horm. Res. Paediatr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1126\/science.1223490","article-title":"Interactions between the microbiota and the immune system","volume":"336","author":"Hooper","year":"2012","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1007\/s00394-015-0900-7","article-title":"Markers of systemic exposures to products of intestinal bacteria in a dietary intervention study","volume":"55","author":"Umoh","year":"2016","journal-title":"Eur. J. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"587","DOI":"10.3389\/fmicb.2014.00587","article-title":"From lifetime to evolution: Timescales of human gut microbiota adaptation","volume":"5","author":"Quercia","year":"2014","journal-title":"Front. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.ebiom.2019.06.031","article-title":"Microbiome and type 1 diabetes","volume":"46","author":"Siljander","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Candon, S., Perez-Arroyo, A., Marquet, C., Valette, F., Foray, A.-P., Pelletier, B., Milani, C., Ventura, M., Bach, J.-F., and Chatenoud, L. (2015). Antibiotics in early life alter the gut microbiome and increase disease incidence in a spontaneous mouse model of autoimmune insulin-dependent diabetes. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0125448"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.jaut.2016.05.001","article-title":"Different immunological responses to early-life antibiotic exposure affecting autoimmune diabetes development in NOD mice","volume":"72","author":"Hu","year":"2016","journal-title":"J. Autoimmun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1007\/s00125-012-2564-7","article-title":"Early life treatment with vancomycin propagates Akkermansia muciniphila and reduces diabetes incidence in the NOD mouse","volume":"55","author":"Hansen","year":"2012","journal-title":"Diabetologia"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4176","DOI":"10.4049\/jimmunol.1500884","article-title":"Maternal antibiotic treatment protects offspring from diabetes development in nonobese diabetic mice by generation of tolerogenic APCs","volume":"195","author":"Hu","year":"2015","journal-title":"J. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/nmicrobiol.2016.140","article-title":"Antibiotic-mediated gut microbiome perturbation accelerates development of type 1 diabetes in mice","volume":"1","author":"Livanos","year":"2016","journal-title":"Nat. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"619","DOI":"10.2337\/db13-1007","article-title":"Induction of Diabetes in the RIP-B7.1 Mouse Model Is Critically Dependent on TLR3 and MyD88 Pathways and Is Associated With Alterations in the Intestinal Microbiome","volume":"63","author":"Alkanani","year":"2013","journal-title":"Diabetes"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"G\u00fclden, E., Ihira, M., Ohashi, A., Reinbeck, A.L., Freudenberg, M.A., Kolb, H., and Burkart, V. (2013). Toll-like receptor 4 deficiency accelerates the development of insulin-deficient diabetes in non-obese diabetic mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0075385"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5645","DOI":"10.4049\/jimmunol.0901814","article-title":"TLR9 blockade inhibits activation of diabetogenic CD8+ T cells and delays autoimmune diabetes","volume":"184","author":"Zhang","year":"2010","journal-title":"J. Immunol."},{"key":"ref_26","first-page":"1109","article-title":"Innate immunity and intestinal microbiota in the development of type 1 diabetes","volume":"455","author":"Wen","year":"2008","journal-title":"Nat. Cell Biol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Brown, C.T., Davis-Richardson, A.G., Giongo, A., Gano, K.A., Crabb, D.B., Mukherjee, N., Casella, G., Drew, J.C., Ilonen, J., and Knip, M. (2011). Gut Microbiome Metagenomics Analysis Suggests a Functional Model for the Development of Autoimmunity for type 1 diabetes. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0025792"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.2337\/db12-0526","article-title":"Fecal microbiota composition differs between children with \u03b2-cell autoimmunity and those without","volume":"62","author":"Knip","year":"2013","journal-title":"Diabetes"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1007\/s00125-014-3274-0","article-title":"Aberrant gut microbiota composition at the onset of type 1 diabetes in young children","volume":"57","author":"Fuentes","year":"2014","journal-title":"Diabetologia"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"De Groot, P.F., Belzer, C., Aydin, \u00d6., Levin, E., Levels, J.H., Aalvink, S., Boot, F., Holleman, F., Van Raalte, D.H., and Scheithauer, T.P. (2017). Distinct fecal and oral microbiota composition in human type 1 diabetes, an observational study. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0188475"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4706","DOI":"10.3390\/nu6114706","article-title":"The influence of early life nutrition on epigenetic regulatory mechanisms of the immune system","volume":"6","author":"Paparo","year":"2014","journal-title":"Nutrients"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/nature12726","article-title":"Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation","volume":"504","author":"Arpaia","year":"2013","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/nature12721","article-title":"Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells","volume":"504","author":"Furusawa","year":"2013","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1080\/19490976.2015.1134082","article-title":"Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism","volume":"7","author":"Morrison","year":"2016","journal-title":"Gut Microbes"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1002\/dmrr.2790","article-title":"Association between intestinal permeability and faecal microbiota composition in Italian children with beta cell autoimmunity at risk for type 1 diabetes","volume":"32","author":"Maffeis","year":"2016","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.chom.2015.01.001","article-title":"The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes","volume":"17","author":"Kostic","year":"2015","journal-title":"Cell Host Microbe"},{"key":"ref_37","first-page":"589","article-title":"The human gut microbiome in early-onset type 1 diabetes from the TEDDY study","volume":"562","author":"Vatanen","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1111\/j.1399-5448.2011.00774.x","article-title":"The environmental determinants of diabetes in the young (TEDDY): Genetic criteria and international diabetes risk screening of 421,000 infants","volume":"12","author":"Hagopian","year":"2011","journal-title":"Pediatr. Diabetes"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1126\/science.1104816","article-title":"Host-bacterial mutualism in the human intestine","volume":"307","author":"Ley","year":"2005","journal-title":"Science"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Durazzo, M., Ferro, A., and Gruden, G. (2019). Gastrointestinal microbiota and type 1 diabetes mellitus: The state of art. J. Clin. Med., 8.","DOI":"10.3390\/jcm8111843"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Murri, M., Leiva, I., Gomez-Zumaquero, J.M., Tinahones, F.J., Cardona, F., Soriguer, F., and Queipo-Ortu\u00f1o, M.I. (2013). Gut microbiota in children with type 1 diabetes differs from that in healthy children: A case-control study. BMC Med., 11.","DOI":"10.1186\/1741-7015-11-46"},{"key":"ref_42","first-page":"3814","article-title":"Fecal microbiota imbalance in Mexican children with type 1 diabetes","volume":"4","author":"Petrosino","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.2337\/dc18-0253","article-title":"Gut microbiota differs in composition and functionality between children with type 1 diabetes and MODY2 and healthy control subjects: A case-control study","volume":"41","author":"Tinahones","year":"2018","journal-title":"Diabetes Care"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1099\/mic.0.000412","article-title":"The intestinal proteome of diabetic and control children is enriched with different microbial and host proteins","volume":"163","author":"Pinto","year":"2017","journal-title":"Microbiology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1042\/BJ20082222","article-title":"The regulation of intestinal mucin MUC2 expression by short-chain fatty acids: Implications for epithelial protection","volume":"420","author":"Paassen","year":"2009","journal-title":"Biochem. J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"289","DOI":"10.4161\/gmic.19897","article-title":"Microbial degradation of complex carbohydrates in the gut","volume":"3","author":"Flint","year":"2012","journal-title":"Gut Microbes"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1079\/PNS19960090","article-title":"The role of butyrate in human colonic epithelial cells: An energy source or inducer of differentiation and apoptosis?","volume":"55","author":"Hague","year":"1996","journal-title":"Proc. Nutr. Soc."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.3945\/jn.109.104638","article-title":"Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers","volume":"139","author":"Peng","year":"2009","journal-title":"J. Nutr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/j.jpeds.2004.06.068","article-title":"Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis","volume":"145","author":"Rosenfeldt","year":"2004","journal-title":"J. Pediatr."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Valladares, R., Sankar, D., Li, N., Williams, E., Lai, K.-K., Abdelgeliel, A.S., Gonzalez, C.F., Wasserfall, C.H., Larkin, J., and Schatz, D. (2010). Lactobacillus johnsonii N6.2 Mitigates the development of type 1 diabetes in BB-DP rats. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010507"},{"key":"ref_51","first-page":"G851","article-title":"Regulation of human epithelial tight junction proteins by lactobacillus plantarum in vivo and protective effects on the epithelial barrier","volume":"298","author":"Karczewski","year":"2010","journal-title":"Am. J. Physiol. Liver Physiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.earlhumdev.2006.12.002","article-title":"The effect of a bifidobacter supplemented bovine milk on intestinal permeability of preterm infants","volume":"83","author":"Stratiki","year":"2007","journal-title":"Early Hum. Dev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"5810","DOI":"10.1128\/AEM.70.10.5810-5817.2004","article-title":"Lactate-utilizing bacteria, isolated from human feces, that produce butyrate as a major fermentation product","volume":"70","author":"Duncan","year":"2004","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"11","DOI":"10.3389\/fendo.2020.00125","article-title":"Evaluating the causal role of gut microbiota in type 1 diabetes and its possible pathogenic mechanisms","volume":"11","author":"Zhou","year":"2020","journal-title":"Front. Endocrinol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/ismej.2010.92","article-title":"Toward defining the autoimmune microbiome for type 1 diabetes","volume":"5","author":"Giongo","year":"2010","journal-title":"ISME J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1001\/jamapediatrics.2015.2757","article-title":"Association of early exposure of probiotics and islet autoimmunity in the TEDDY study","volume":"170","author":"Uusitalo","year":"2016","journal-title":"JAMA Pediatr."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4427","DOI":"10.1210\/jc.2019-00481","article-title":"Effect of prebiotic on microbiota, intestinal permeability and glycemic control in children with type 1 diabetes","volume":"104","author":"Ho","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_58","first-page":"56","article-title":"Diet\u2013microbiota interactions as moderators of human metabolism","volume":"535","author":"Sonnenburg","year":"2016","journal-title":"Nat. Cell Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13073-016-0299-7","article-title":"An expansion of rare lineage intestinal microbes characterizes rheumatoid arthritis","volume":"8","author":"Chen","year":"2016","journal-title":"Genome Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"12015","DOI":"10.1038\/ncomms12015","article-title":"Alterations of the human gut microbiome in multiple sclerosis","volume":"7","author":"Jangi","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"471","DOI":"10.3945\/ajcn.111.018879","article-title":"Food consumption and advanced \u03b2 cell autoimmunity in young children with HLA-conferred susceptibility to type 1 diabetes: A nested case-control design","volume":"95","author":"Virtanen","year":"2012","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1007\/s00125-015-3614-8","article-title":"A model for the role of gut bacteria in the development of autoimmunity for type 1 diabetes","volume":"58","author":"Triplett","year":"2015","journal-title":"Diabetologia"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/pedi.12115","article-title":"The effect of childhood cow\u2019s milk intake and HLA-DR genotype on risk of islet autoimmunity and type 1 diabetes: The Diabetes autoimmunity study in the young","volume":"16","author":"Lamb","year":"2015","journal-title":"Pediatr. Diabetes"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1007\/BF02221682","article-title":"Concordance for type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus in a population-based cohort of twins in Finland","volume":"35","author":"Kaprio","year":"1992","journal-title":"Diabetologia"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1016\/j.cell.2018.10.029","article-title":"US immigration westernizes the human gut microbiome","volume":"175","author":"Vangay","year":"2018","journal-title":"Cell"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12967-017-1175-y","article-title":"Influence of diet on the gut microbiome and implications for human health","volume":"15","author":"Singh","year":"2017","journal-title":"J. Transl. Med."},{"key":"ref_67","first-page":"181","article-title":"Artificial sweeteners induce glucose intolerance by altering the gut microbiota","volume":"514","author":"Suez","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"589","DOI":"10.2337\/diab.46.4.589","article-title":"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","volume":"46","author":"Scott","year":"1997","journal-title":"Diabetes"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.2337\/diacare.17.12.1381","article-title":"Environmental factors in childhood IDDM: A population-based, case-control study","volume":"17","author":"Verge","year":"1994","journal-title":"Diabetes Care"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1053\/j.gastro.2008.03.023","article-title":"Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3","volume":"135","author":"Lammers","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Haupt-Jorgensen, M., Holm, L.J., Josefsen, K., and Buschard, K. (2018). Possible prevention of diabetes with a gluten-free diet. Nutrients, 10.","DOI":"10.3390\/nu10111746"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fendo.2020.00078","article-title":"The role of gut microbiota and environmental factors in type 1 diabetes pathogenesis","volume":"11","author":"Dedrick","year":"2020","journal-title":"Front. Endocrinol."},{"key":"ref_73","first-page":"1445","article-title":"Akkermansia muciniphila induces gut microbiota remodelling and controls islet autoimmunity in NOD mice","volume":"67","author":"Toivonen","year":"2017","journal-title":"Gut"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1001\/jama.290.13.1721","article-title":"Early infant feeding and risk of developing type 1 diabetes\u2013Associated autoantibodies","volume":"290","author":"Ziegler","year":"2003","journal-title":"JAMA"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1001\/jama.290.13.1713","article-title":"Timing of initial cereal exposure in infancy and risk of islet autoimmunity","volume":"290","author":"Norris","year":"2003","journal-title":"JAMA"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1159\/000073710","article-title":"Pathomechanisms in celiac disease","volume":"132","author":"Dieterich","year":"2003","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1136\/adc.2002.012799","article-title":"Effect of gluten-free diet and adherence on growth and diabetic control in diabetics with coeliac disease","volume":"89","author":"Saadah","year":"2004","journal-title":"Arch. Dis. Child."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1002\/dmrr.609","article-title":"Diabetes preventive gluten-free diet decreases the number of caecal bacteria in non-obese diabetic mice","volume":"22","author":"Hansen","year":"2006","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1097\/01.mpg.0000174846.67797.87","article-title":"Screening detected celiac disease in children with type 1 diabetes mellitus: Effect on the clinical course (A case control study)","volume":"41","author":"Rami","year":"2005","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1515\/JPEM.1999.12.3.433","article-title":"Children with coeliac disease and insulin dependent diabetes mellitus\u2014Growth, diabetes control and dietary intake","volume":"12","author":"Westman","year":"1999","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"984","DOI":"10.2337\/diacare.16.7.984","article-title":"The childhood diabetes in Finland study group increased levels of cow\u2019s milk and -lactoglobulin antibodies in young children with newly diagnosed IDDM","volume":"16","author":"Savilahti","year":"1993","journal-title":"Diabetes Care"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Robertson, L., and Harrild, K. (2010). Maternal and neonatal risk factors for childhood type 1 diabetes: A matched case-control study. BMC Public Health, 10.","DOI":"10.1186\/1471-2458-10-281"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s00394-009-0008-z","article-title":"Early infant feeding and type 1 diabetes","volume":"48","author":"Savilahti","year":"2009","journal-title":"Eur. J. Nutr."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1001\/archpediatrics.2011.1559","article-title":"Removal of bovine insulin from cow\u2019s milk formula and early initiation of beta-cell autoimmunity in the FINDIA pilot study","volume":"166","author":"Vaarala","year":"2012","journal-title":"Arch. Pediatr. Adolesc. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1001\/jamapediatrics.2017.0378","article-title":"Association between breast milk bacterial communities and establishment and development of the infant gut microbiome","volume":"171","author":"Pannaraj","year":"2017","journal-title":"JAMA Pediatr."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.molmed.2014.12.002","article-title":"The infant microbiome development: Mom matters","volume":"21","author":"Mueller","year":"2015","journal-title":"Trends Mol. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1159\/000220416","article-title":"Influence of early nutritional components on the development of murine autoimmune diabetes","volume":"54","author":"Mueller","year":"2009","journal-title":"Ann. Nutr. Metab."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1089\/bfm.2011.0009","article-title":"Breastfeeding protects against type 1 diabetes mellitus: A case\u2013sibling study","volume":"7","author":"Alves","year":"2012","journal-title":"Breastfeed. Med."},{"key":"ref_89","first-page":"257","article-title":"Infant feeding in relation to islet autoimmunity and type 1 diabetes in genetically susceptible children: The MIDIA study","volume":"38","author":"Stene","year":"2014","journal-title":"Diabetes Care"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1017\/S0007114507210189","article-title":"For the ABIS study group short duration of breast-feeding as a risk-factor for \u03b2-cell autoantibodies in 5-year-old children from the general population","volume":"97","author":"Holmberg","year":"2007","journal-title":"Br. J. Nutr."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1002\/dmrr.425","article-title":"Longer breastfeeding is an independent protective factor against development of type 1 diabetes mellitus in childhood","volume":"20","author":"Ludvigsson","year":"2004","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Mishra, S.P., Wang, S., Nagpal, R., Miller, B., Singh, R., Taraphder, S., and Yadav, H. (2019). Probiotics and prebiotics for the amelioration of type 1 diabetes: Present and future perspectives. Microorganism, 7.","DOI":"10.3390\/microorganisms7030067"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1111\/cei.12293","article-title":"Intestinal microbiota and faecal transplantation as treatment modality for insulin resistance and type 2 diabetes mellitus","volume":"177","author":"Udayappan","year":"2014","journal-title":"Clin. Exp. Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13099-019-0332-7","article-title":"Is there any association between gut microbiota and type 1 diabetes? A systematic review","volume":"11","author":"Jamshidi","year":"2019","journal-title":"Gut Pathog."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1111\/1753-0407.12915","article-title":"Current understanding of the role of gut dysbiosis in type 1 diabetes","volume":"11","author":"Abdellatif","year":"2019","journal-title":"J. Diabetes"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"e3043","DOI":"10.1002\/dmrr.3043","article-title":"Gut microbiome in type 1 diabetes: A comprehensive review","volume":"34","author":"Zheng","year":"2018","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Han, H., Li, Y., Fang, J., Liu, G., Yin, J., Li, T., and Yin, Y. (2018). Gut microbiota and type 1 diabetes. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19040995"},{"key":"ref_98","first-page":"36","article-title":"Kidney function improvement by soy milk containing lactobacillus plantarum A7 in type 2 diabetic patients with nephropathy: A double-blinded randomized controlled trial","volume":"11","author":"Abbasi","year":"2017","journal-title":"Iran. J. Kidney Dis."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Firouzi, S., Mohd-Yusof, B.-N., Majid, H.-A., Ismail, A., and Kamaruddin, N.-A. (2015). Effect of microbial cell preparation on renal profile and liver function among type 2 diabetics: A randomized controlled trial. BMC Complementary Altern. Med., 15.","DOI":"10.1186\/s12906-015-0952-5"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"4763","DOI":"10.1039\/C8FO00888D","article-title":"Metabolic and genetic response to probiotics supplementation in patients with diabetic nephropathy: A randomized, double-blind, placebo-controlled trial","volume":"9","author":"Mafi","year":"2018","journal-title":"Food Funct."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.kint.2016.09.040","article-title":"Probiotic supplementation in diabetic hemodialysis patients has beneficial metabolic effects","volume":"91","author":"Soleimani","year":"2017","journal-title":"Kidney Int."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1007\/s12602-018-9468-x","article-title":"The effects of pro-biotic honey consumption on metabolic status in patients with diabetic nephropathy: A randomized, double-blind, controlled trial","volume":"11","author":"Tavakolipour","year":"2019","journal-title":"Probiotics Antimicrob Proteins"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1053\/j.jrn.2017.04.004","article-title":"The impact of probiotic soy milk consumption on oxidative stress among type 2 diabetic kidney disease patients: A randomized controlled clinical trial","volume":"27","author":"Miraghajani","year":"2017","journal-title":"J. Ren. Nutr."},{"key":"ref_104","first-page":"4961","article-title":"Effects of probiotic on the development of diabetic retinopathy","volume":"61","author":"Homme","year":"2020","journal-title":"ARVO Annu. Meet."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13098-018-0353-2","article-title":"The effects of probiotic supplementation on metabolic status in type 2 diabetic patients with coronary heart disease","volume":"10","author":"Raygan","year":"2018","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"33","DOI":"10.2337\/db18-33-LB","article-title":"Recombinant probiotics expressing angiotensin-(1-7) improves glucose metabolism and diabetes-induced renal and retinal injury","volume":"67","author":"Li","year":"2018","journal-title":"Diabetes"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13063-016-1486-y","article-title":"Effect of prebiotic intake on gut microbiota, intestinal permeability and glycemic control in children with type 1 diabetes: Study protocol for a randomized controlled trial","volume":"17","author":"Ho","year":"2016","journal-title":"Trials"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1136\/gut.2008.165886","article-title":"Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability","volume":"58","author":"Cani","year":"2009","journal-title":"Gut"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1136\/gutjnl-2020-322630","article-title":"Faecal microbiota transplantation halts progression of human new-onset type 1 diabetes in a randomised controlled trial","volume":"70","author":"Nikolic","year":"2021","journal-title":"Gut"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1089\/omi.2018.0053","article-title":"Type 2 diabetes mellitus: Integrative analysis of multiomics data for biomarker discovery","volume":"22","author":"Ge","year":"2018","journal-title":"OMICS J. Integr. Biol."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Collares, C.V.A., Evangelista, A.F., Xavier, D.J., Rassi, D.M., Arns, T., Foss-Freitas, M.C., Foss, M.C., Puthier, D., Sakamoto-Hojo, E.T., and Passos, G.A. (2013). Identifying common and specific microRNAs expressed in peripheral blood mononuclear cell of type 1, type 2, and gestational diabetes mellitus patients. BMC Res. Notes, 6.","DOI":"10.1186\/1756-0500-6-491"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"e89656","DOI":"10.1172\/jci.insight.89656","article-title":"Profiling of circulating microRNAs in children with recent onset of type 1 diabetes","volume":"2","author":"Erener","year":"2017","journal-title":"JCI Insight"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mce.2019.03.008","article-title":"Post-transcriptional markers associated with clinical complications in type 1 and type 2 diabetes mellitus","volume":"490","author":"Massaro","year":"2019","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1021\/acs.jproteome.6b00354","article-title":"Tracking the antibody immunome in type 1 diabetes using protein arrays","volume":"16","author":"Bian","year":"2016","journal-title":"J. Proteome Res."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Gan, W.Z., Ramachandran, V., Lim, C.S.Y., and Koh, R.Y. (2019). Omics-based biomarkers in the diagnosis of diabetes. J. Basic Clin. Physiol. Pharmacol., 31.","DOI":"10.1515\/jbcpp-2019-0120"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1111\/1753-0407.12645","article-title":"Diabetes and branched-chain amino acids: What is the link?","volume":"10","author":"Bloomgarden","year":"2018","journal-title":"J. Diabetes"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"718","DOI":"10.2337\/db14-0509","article-title":"Metabolomics and diabetes: Analytical and computational approaches","volume":"64","author":"Sas","year":"2015","journal-title":"Diabetes"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2019\/2893041","article-title":"Metagenomics and faecal metabolomics integrative analysis towards the impaired glucose regulation and type 2 diabetes in uyghur-related omics","volume":"2019","author":"Nuli","year":"2019","journal-title":"J. Diabetes Res."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Li, B., He, X., Jia, W., and Li, H. (2017). Novel applications of metabolomics in personalized medicine: A mini-review. Molecules, 22.","DOI":"10.3390\/molecules22071173"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.aca.2011.01.034","article-title":"Plasma esterified and non-esterified fatty acids metabolic profiling using gas chromatography\u2013mass spectrometry and its application in the study of diabetic mellitus and diabetic nephropathy","volume":"689","author":"Han","year":"2011","journal-title":"Anal. Chim. Acta"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"791","DOI":"10.2337\/db13-0396","article-title":"BMI, RQ, diabetes, and sex affect the relationships between amino acids and clamp measures of insulin action in humans","volume":"63","author":"Ingram","year":"2014","journal-title":"Diabetes"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/5\/2763\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:35:26Z","timestamp":1760160926000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/5\/2763"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,9]]},"references-count":121,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["ijms22052763"],"URL":"https:\/\/doi.org\/10.3390\/ijms22052763","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,9]]}}}