Aron Arzoomand, MD: No financial relationships to disclose
Introduction/Rationale: Breastfeeding provides infants – globally – with a uniform nutritional foundation that selectively promotes gut microbes that guide immune development. Breast milk (BM) derived microbial breakdown products in stool and plasma are today still largely unexplored, and likely play a major role in mediating the immunoprotective effects associated with BM.
Methods: We aimed to characterize these products using a carefully curated cohort of BM and exclusively formula (F) fed infants (nbreastmilk = 54, nformula = 17) in stool and plasma at both 3 months and 6 months of age using untargeted MS/MS protocols. Stool metagenomes were also generated and annotated for metabolic pathways. Blood was also processed for bulk mRNA sequencing, cell population frequencies, plasma proteome, and immunoglobulin glycosylations.
Results: Applying supervised discriminatory models we identified > 11’000 metabolites in stool and plasma collectively that could accurately discriminate BM and F fed infants at 3 months of age, with BM effects persisting at 6 months of age even after the introduction solid food. In the gut BM fed infants were selectively colonized with Bacteroides and Bifidobacterium species which we show harbor enzymes to liberate fucose from milk saccharides and mucins. Consistently these infants show increased concentrations of fucose in plasma and a parallell increases in core-fucosylated plasma IgA. The role of circulating IgA remains to be dissected but preliminarily our data suggests gut microbial regulation of humoral IgA responses in BM fed infants via altered glycosylation patterns.
Conclusion: Immune-microbe interactions must be established early after birth. Here we report on a symbiotic nutritional dialogue largely reserved to BM fed infants, and parallell changes to their circulating and fucosylated IgA repository. This offers a novel perspective into how breastmilk and microbial interactions shape the developing immune system, and how absence of these mechanisms could influence disease susceptibility.
