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Understanding the role of Clostridioides difficile and Vitamin D supplementation in shaping the gut microbiome of Canadian infants

  • Author / Creator
    Drall, Kelsea Michelle
  • Introduction: The gut microbiome is shaped during infancy and has an important role in the development of both the immune and metabolic systems. Many early life exposures and events contribute to the composition of this complex intestinal environment, notably early infant diet and breastfeeding. Clostridioides difficile colonization occurs in up to half of infants under the age of 3 months and is strongly predicted by formula feeding. Although this microbe does not appear to pose any immediate risks for infants (colonization is largely asymptomatic), its presence has been associated with susceptibility to chronic disease later in childhood, perhaps by promoting changes in the gut microbiome including increased opportunity for colonization with other pathogenic bacteria. Infant feeding (breast and formula) has an important role in shaping gut microbiome and predicting C. difficile colonization, yet little is known about the relationship between Vitamin D and the gut microbiome of young infants. Meanwhile, Vitamin D supplementation is recommended by pediatric health professionals in Canada for all breastfed infants, and many maternal multivitamins/prenatal vitamins contain Vitamin D which could influence the Vitamin D intake of infants during pregnancy and lactation. Vitamin D has also been associated with changes to the microbiome and C. difficile abundance in infancy, thus meriting further investigation. Objectives: This thesis aims to describe the differences in gut microbiome according to C. difficile colonization status and breastfeeding status (Study 1) and determine if maternal and infant intake of an important micronutrient, Vitamin D, is associated with C. difficile colonization in breastfed infants at 3 months of age (Study 2). Methods: Study 1 is a descriptive analysis conducted on 1562 infants whose mothers were enrolled at the Edmonton, Vancouver or Winnipeg Canadian Healthy Infant Longitudinal Development Study sites. Study 2 was a cross-sectional analysis conducted on 1157 mother/infant pairs. All participants had complete data describing breastfeeding status at 3 months and each provided a stool sample which was profiled using 16S rRNA sequencing and targeted detection of C. difficile with real time qPCR. Fecal metabolites and sIgA were also detected using NMR and an Immundiagnostik ELISA kit. Parametric and non-parametric tests, where appropriate, were used to describe the relationship between C. difficile colonization, Vitamin D supplement intake, metabolites, sIgA and gut microbiome diversity. Multivariate linear regression (MaAslin) was used to determine associations between C. difficile and the gut microbiota composition (Study 1) as well as Vitamin D supplementation and the gut microbiota composition (Study 2). PERMANOVA was used to determine the significance of global diversity changes (beta diversity) with C. difficile colonization. Logistic regression analyses were performed to determine the association between Vitamin D supplementation and C. difficile colonization, while adjusting for relevant covariates. Results: C. difficile colonization was differentially associated with gut microbiome changes in breastfed versus formula fed infants, with more notable differences among exclusively breastfed infants and very few among exclusively formula fed infants. These changes included increased alpha diversity, significant between sample heterogeneity (beta-diversity), decreased fecal sIgA, increased abundance of Firmicutes, decreased Bifidobacteriaceae and increased concentrations of SCFA’s in those colonized with C. difficile relative to non-carriers. Neither maternal (pre or post-natal) nor infant Vitamin D supplementation was associated with C. difficile colonization at 3 months of age.Conclusion: The findings of Study 1 provide evidence of important differences in the infant gut microbiome development between C. difficile carriers and non-carriers, particularly in exclusively breastfed infants. Upon exploring a possible predictor of C. difficile colonization in exclusively breastfed infants (Study 2), we found no significant association between Vitamin D supplementation and C. difficile carriage. Thus, current guidelines surrounding Vitamin D supplementation do not appear to influence C. difficile colonization.

  • Subjects / Keywords
  • Graduation date
    Spring 2019
  • Type of Item
    Thesis
  • Degree
    Master of Science
  • DOI
    https://doi.org/10.7939/r3-zdfs-4k55
  • License
    Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.