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UBC Theses and Dissertations

Early-life gut microbiota dysbiosis in children with atopic dermatitis Cutler, Chelsea


Introduction: Atopic dermatitis (AD) is a prevalent, heterogeneous allergic disease of the skin, impacting quality of life and often a prelude to other incurable allergic diseases. Microbes residing in the gut in early-life play an important role in shaping the function of the immune system and may be critical in the prevention or treatment of AD. Characterizing the early-life gut microbiota in children with AD may lead to new therapeutic and preventative measures involving alteration of the gut microbiota. Hypotheses: The specific hypotheses tested in this study are: 1) there is dysbiosis (or imbalance) in the gut microbiota of infants with clinically relevant AD phenotypes; and 2) there are differences in gut microbiota composition between extrinsic and intrinsic AD endotypes. Methods: Leveraging stool samples and data from the Canadian Healthy Infant Longitudinal Development (CHILD) study, early-life gut microbiota of deeply phenotyped children with AD was assessed. AD at five years of age, moderate/severe AD, and persistent AD phenotypes and intrinsic and extrinsic AD endotypes were formalized. 16S rRNA gene sequencing was used to analyze stool samples to assess gut microbial diversity, maturation and taxa abundance between phenotypes and healthy controls. Results: Gut microbial diversity and maturation was significantly decreased in children with AD at five years of age compared to healthy controls. Epulopiscium, Aggregatibacter, Turicibater, Phascolarctobacterium, Citrobacter and Prevotella were detected at significantly different levels in the early-life gut microbiota of infants with clinically-relevant AD and healthy controls. Microbial diversity and gut maturation indices in children with extrinsic AD were significantly decreased compared to healthy controls, whereas children with intrinsic AD had no differences in diversity or gut maturation compared to healthy controls. Taxa abundance were different between intrinsic and extrinsic AD endotypes. Conclusion: There are differences in the early-life gut microbiota of children with various clinically-relevant AD phenotypes compared to children without AD. Thoroughly phenotyping AD is important for proper treatment or prevention, particularly for considering gut microbiota alteration as a therapeutic method. This knowledge contributes to the process of profiling the gut microbiota of children with AD with the goal of creating live biotherapeutics for prevention of AD.

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