Understanding the role of Clostridioides difficile and Vitamin D supplementation in shaping the gut microbiome of Canadian infants
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.002 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".