Microbiota and Metabolomic Patterns in the Breast Milk of Subjects with Celiac Disease on a Gluten-Free Diet

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.

Interrogating the role of the milk microbiome in mastitis in the multi-omics era

“…While this approach can provide information on taxonomic composition, metagenomics can go beyond this application and provide insight into both species and subspecies diversity and functional potential by examining the gene sequences that encode for proteins or functional RNAs (e.g., mRNAs and noncoding RNA). A handful of studies have utilized metagenomic sequencing to characterize the composition of the milk microbiome in bovine ( Bhatt et al, 2012 ; Patel et al, 2017 ; Kusumawati et al, 2021 ) and human ( Jiménez et al, 2015 ; Kordy et al, 2020 ; Seferovic et al, 2020 ; Olshan et al, 2021 ) milk but very few have interrogated the functional potential of the microbial communities. Metagenomic deep sequencing was used to compare the microbiomes of milk obtained from cows with clinical mastitis and healthy control cows where functional annotation of the metagenomic sequences was performed to identify differences in metabolic pathways ( Hoque et al, 2019 ).…”

“…Some recent studies have looked at the milk metabolome and microbiome composition in the context of infant health and maternal diet. Shotgun metagenomics and metabolomics were used to identify significant differences in bacterial and viral species/strains and pathways in the breast milk of subjects with celiac disease on a gluten free diet ( Olshan et al, 2021 ). In another study, metabolome and microbiome profiles of milk produced by women across several countries were compared using NMR and 16S rRNA gene sequencing to reveal specific metabolite profile associations with geographical locations ( Gomez-Gallego et al, 2018 ).…”

Cohort profile: Celiac disease genomic, environmental, microbiome and metabolome study; a prospective longitudinal birth cohort study of children at-risk for celiac disease

“…In other work we utilized a multi-omic approach to examine the microbiota and metabolome of breast milk from mothers enrolled in the CDGEMM study with CD compared to those without CD [20]. We identified differences in bacterial and viral species/strains and in functional pathways between these two groups.…”

Manipulation of the gut microbiome in gluten-intolerance

“…Theoretically, these microbiota taxa could be vertically transmitted from mothers-to-infants during breastfeeding, thereby influencing CeD risk [5]. More recently, the analysis of the breast milk microbiota from mothers with CeD detected an increase in the relative abundance of Acinetobacter ursingii , Rothia mucilaginosa , and Acintobacteria, and reductions in Faecalibacterium prausnitzii , Clostridiales , and Gemella [11].…”