Abstract

The intestinal microbiome may trigger celiac disease (CD) in individuals with a genetic disposition when exposed to dietary gluten. Research demonstrates that nutrition during infancy is crucial to the intestinal microbiome engraftment. Very few studies to date have focused on the breast milk composition of subjects with a history of CD on a gluten-free diet. Here, we utilize a multi-omics approach with shotgun metagenomics to analyze the breast milk microbiome integrated with metabolome profiling of 36 subjects, 20 with CD on a gluten-free diet and 16 healthy controls. These analyses identified significant differences in bacterial and viral species/strains and functional pathways but no difference in metabolite abundance. Specifically, three bacterial strains with increased abundance were identified in subjects with CD on a gluten-free diet of which one (Rothia mucilaginosa) has been previously linked to autoimmune conditions. We also identified five pathways with increased abundance in subjects with CD on a gluten-free diet. We additionally found four bacterial and two viral species/strains with increased abundance in healthy controls. Overall, the differences observed in bacterial and viral species/strains and in functional pathways observed in our analysis may influence microbiome engraftment in neonates, which may impact their future clinical outcomes.

Highlights

  • Celiac disease (CD) is an autoimmune enteropathy triggered by ingestion of gluten, a protein found in wheat, rye, and barley [1]

  • All subjects included in our analysis provided a breast milk sample at 7–14 days after parturition

  • Thirty-six subjects with transitional breast milk samples available at 7–14 days after parturition were selected for analysis

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Summary

Introduction

Celiac disease (CD) is an autoimmune enteropathy triggered by ingestion of gluten, a protein found in wheat, rye, and barley [1]. This disease occurs only in individuals with specific human leukocyte antigen (HLA) DQ haplotypes (DQ2, DQ8) [1]. While 30% of the population carries these compatible genetics, only 2–3% of these individuals develop CD [2]. This implies that genetic predisposition and exposure to dietary gluten are necessary but not sufficient to develop CD. While early studies suggest that formula feeding during infancy is associated with an increased risk of developing CD [8], subsequent prospective studies have not found that breastfeeding was protective against developing CD [3,4]

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