Abstract

Diet-microbe interactions play an important role in modulating the early-life microbiota, with Bifidobacterium strains and species dominating the gut of breast-fed infants. Here, we sought to explore how infant diet drives distinct bifidobacterial community composition and dynamics within individual infant ecosystems. Genomic characterisation of 19 strains isolated from breast-fed infants revealed a diverse genomic architecture enriched in carbohydrate metabolism genes, which was distinct to each strain, but collectively formed a pangenome across infants. Presence of gene clusters implicated in digestion of human milk oligosaccharides (HMOs) varied between species, with growth studies indicating that within single infants there were differences in the ability to utilise 2′FL and LNnT HMOs between strains. Cross-feeding experiments were performed with HMO degraders and non-HMO users (using spent or ‘conditioned’ media and direct co-culture). Further 1H-NMR analysis identified fucose, galactose, acetate, and N-acetylglucosamine as key by-products of HMO metabolism; as demonstrated by modest growth of non-HMO users on spend media from HMO metabolism. These experiments indicate how HMO metabolism permits the sharing of resources to maximise nutrient consumption from the diet and highlights the cooperative nature of bifidobacterial strains and their role as ‘foundation’ species in the infant ecosystem. The intra- and inter-infant bifidobacterial community behaviour may contribute to the diversity and dominance of Bifidobacterium in early life and suggests avenues for future development of new diet and microbiota-based therapies to promote infant health.

Highlights

  • When human milk oligosaccharides (HMOs) utilisation was tested in type strains for B. longum, B. infantis, and B. pseudocatenulatum we found there was not a global ability of all strains within a species of Bifidobacterium to utilise HMOs (Fig. S5B), demonstrating that HMO utilisation is dependent on the type of HMO and the strain tested

  • Bifidobacterium spp. are central players in the early-life microbiota and healthy infant development. We show that this genus is present at very high levels in breast-fed infants, and that distinct bifidobacterial communities exist within an individual infant, consistent with other findings [47]

  • Our data indicate differences in genomic content for these individual strains, which links to their ability to thrive on breast milk-associated dietary components like HMOs by multiple members of Bifidobacterium within a single infant (‘community’)

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Summary

Present address

APC Microbiome Ireland, University College Cork, Biosciences Building, Cork, Ireland. Previous work has indicated that multiple Bifidobacterium strains coexist in a single infant GI tract, rather than one strain dominating and competitively excluding all other strains [21] To investigate these key community dynamic questions, we have probed the genomic and phenotypic similarities between bifidobacterial strains that coexist in the same individual, including their responses to specific early-life diet components, namely HMOs. By examining microbial interactions on a strain-level we provide important insights into how multiple species of Bifidobacterium coexist within a single infant in early life, which may have implications for design of diet- and microbial-based early-life therapies

Results
Discussion
Methods
Compliance with ethical standards

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