The Effects of IgA Deficiency and Maternal Dysbiosis on Type I Diabetes Incidence

• Author / Creator

  Strachan, Erin R

• There is a growing appreciation for the role of gastrointestinal (GI) health in promoting whole body wellbeing. Key features of a healthy gut include a balanced microbiota and their interaction with host immune defense mechanisms such as the production of Immunoglobulin A (IgA). Synergistically, the microbiota and IgA work to preserve the integrity of the gut barrier and regulate immune responses both locally and
  systemically. During infancy, both the microbiota and immune system undergo rapid development and are strongly influenced by maternal factors, conveyed largely via events in the neonatal GI tract. When these events fail to occur at appropriate times, the long term detrimental effects resulting from suboptimal immune development can contribute to subsequent development of pathologies such as Type 1 Diabetes (T1D), where the erroneous activation of autoreactive lymphocytes leads to the destruction of the pancreatic beta cells. Despite the well-documented importance of maternal factors on infant immune development, whether maternal immune dysregulation and dysbiosis can perpetuate the same in offspring remains largely unknown. To gain an understanding of how these maternal factors impact infant disease development, I used IgA-deficiency induced maternal dysbiosis in Non-Obese Diabetic (NOD) dams to study T1D development in their offspring. I found that maternal dysbiosis arising from IgA deficiency results in numerous neonatal changes in IgA-sufficient offspring, including increased GI immune cell numbers and
  cytokine production, increased gut inflammation, altered gut microbiome composition and a modified GI metabolomic profile. In adulthood, IgA-sufficient offspring born to IgA-deficient dams show lessened insulitis and a lower incidence of T1D overall as compared to those reared by IgA-sufficient dams. Cross-fostering experiments indicate this protective effect is mediated post-natally, leading me to hypothesize that maternal microbiome transfer plays a significant role. I am currently exploring various characteristics of breast milk from IgA deficient dams as well as conducting fecal microbiota transfer experiments to explore how this protective effect may be mediated.

• Subjects / Keywords

  • type 1 diabetes
  • maternal dysbiosis
  • autoimmunity
  • neonatal immunity
  • immunoglobulin A

• Graduation date

  Spring 2024

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/r3-qne7-ee34

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.