Details

Autor(en) / Beteiligte

• Kemppainen, Kaisa Mari

Titel

Microbial Connections to Autoimmunity for Type 1 Diabetes and Celiac Disease

Ort / Verlag

ProQuest Dissertations & Theses

Erscheinungsjahr

2016

Quelle

ProQuest Dissertations & Theses A&I

Beschreibungen/Notizen

• Type 1 diabetes (Ti D) and celiac disease (CD) are autoimmune diseases characterized by a T-cell mediated destruction of pancreatic islet-cells and intestinal epithelial cells, respectively. The incidence of both diseases has increased in the last half century. A strong genetic component explains part of the heritability of both disorders, but the reasons for increasing incidence remains unexplained. Numerous environmental factors are thought to play a role in the development of both Ti D and CD, including microbial players such as pathogenic microbes and commensal bacteria inhabiting the gut, collectively known as the microbiome. The aim of this dissertation work is to investigate the effects of microbial exposures in early life on the development of autoimmunity, specifically that of Ti D and CD. The Environmental Determinants of Diabetes in the Young (TEDDY) study was designed to investigate the environmental and genetic factors that contribute to the development of Ti D and/or CD. This multinational prospective study follows over 8,000 children from birth until adolescence. This dissertation work examines the early life microbiome of healthy children enrolled in the TEDDY study, to establish a baseline for early life exposures. Then the association between antibiotic use and development of autoimmunity is explored, to decipher the effects of bacterial depletion on the risk of autoimmunity. Lastly, the effects of childhood infection on the development of CD autoimmunity are determined. The results of this work suggest that geographical location has a definitive impact on the developing microbiome of infants with similar HLA-genotypes. It also provides further proof that the use of 13-lactam antibiotic and macrolides is not a risk factor for the development of autoimmunity for Ti D or CD and antibiotic-induced changes to the microbiome do not affect disease risk. Lastly these results supports the role of viral infections in the development of CD in early life, as gastrointestinal infections occurring several months prior to seroconversion increase the risk of CD autoimmunity in nonHLA-DQ2 children who experience short duration of breastfeeding, and in those children born in the fall who are introduced to gluten early in life. (Full text of this dissertation may be available via the University of Florida Libraries web site. Please check http://www.uflib.ufl.edu/etd.html)