{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:45:17Z","timestamp":1790401517605,"version":"4.1.0"},"reference-count":79,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2019,7,16]],"date-time":"2019-07-16T00:00:00Z","timestamp":1563235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2019,7,16]],"date-time":"2019-07-16T00:00:00Z","timestamp":1563235200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2019,7,16]],"date-time":"2019-07-16T00:00:00Z","timestamp":1563235200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,9,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Alterations in the composition of the intestinal microbiota have been associated with development of type 1 diabetes (T1D), but little is known about changes in intestinal homeostasis that contribute to disease pathogenesis. Here, we analyzed oral tolerance induction, components of the intestinal barrier, fecal microbiota, and immune cell phenotypes in non-obese diabetic (NOD) mice during disease progression compared to non-obese diabetes resistant (NOR) mice. NOD mice failed to develop oral tolerance and had defective protective\/regulatory mechanisms in the intestinal mucosa, including decreased numbers of goblet cells, diminished mucus production, and lower levels of total and bacteria-bound secretory IgA, as well as an altered IEL profile. These disturbances correlated with bacteria translocation to the pancreatic lymph node possibly contributing to T1D onset. The composition of the fecal microbiota was altered in pre-diabetic NOD mice, and cross-fostering of NOD mice by NOR mothers corrected their defect in mucus production, indicating a role for NOD microbiota in gut barrier dysfunction. NOD mice had a reduction of CD103+ dendritic cells (DCs) in the MLNs, together with an increase of effector Th17 cells and ILC3, as well as a decrease of Th2 cells, ILC2, and Treg cells in the small intestine. Importantly, most of these gut alterations precede the onset of insulitis. Disorders in the intestinal mucosa of NOD mice can potentially interfere with the development of T1D due the close relationship between the gut and the pancreas. Understanding these early alterations is important for the design of novel therapeutic strategies for T1D prevention.<\/jats:p>","DOI":"10.1002\/jlb.3hi0119-024rr","type":"journal-article","created":{"date-parts":[[2019,7,17]],"date-time":"2019-07-17T00:31:08Z","timestamp":1563323468000},"page":"513-529","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["Frontline Science: Abnormalities in the gut mucosa of non-obese diabetic mice precede the onset of type 1 diabetes"],"prefix":"10.1093","volume":"106","author":[{"given":"Mariana Camila Gon\u00e7alves","family":"Miranda","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael Pires","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Instituto Federal do Paran\u00e1 , Palmas, Paran\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00edcia","family":"Torres","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah Le\u00e3o Fiorini","family":"Aguiar","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Pinheiro-Rosa","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu\u00edsa","family":"Lemos","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro Andrade","family":"Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Reis","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiany","family":"Silveira","sequence":"additional","affiliation":[{"name":"Departamento de Patologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00canio","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Departamento de Patologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tha\u00eds Garcias","family":"Moreira","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise Carmona","family":"Cara","sequence":"additional","affiliation":[{"name":"Departamento de Morfologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiani Uceli","family":"Maioli","sequence":"additional","affiliation":[{"name":"Departamento de Nutri\u00e7\u00e3o, Escola de Enfermagem, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L","family":"Kelsall","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, NIAID, National Institutes of Health , Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Carlos","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Universidade de S\u00e3o Paulo , Ribeir\u00e3o Preto, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Maria Caetano","family":"Faria","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais, Brazil"},{"name":"Instituto de Investiga\u00e7\u00e3o em Imunologia (iii) , S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,7,16]]},"reference":[{"issue":"9446","key":"2023032406301941200_jlb10458-cit-0001","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1016\/S0140-6736(04)17357-1","article-title":"The rising incidence of childhood type 1 diabetes and reduced contribution of high-risk HLA 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