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 1 H-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.
Summary Supplementation with members of the early-life microbiota as “probiotics” is increasingly used in attempts to beneficially manipulate the preterm infant gut microbiota. We performed a large observational longitudinal study comprising two preterm groups: 101 infants orally supplemented with Bifidobacterium and Lactobacillus (Bif/Lacto) and 133 infants non-supplemented (control) matched by age, sex, and delivery method. 16S rRNA gene profiling on fecal samples (n = 592) showed a predominance of Bifidobacterium and a lower abundance of pathobionts in the Bif/Lacto group. Metabolomic analysis showed higher fecal acetate and lactate and a lower fecal pH in the Bif/Lacto group compared to the control group. Fecal acetate positively correlated with relative abundance of Bifidobacterium, consistent with the ability of the supplemented Bifidobacterium strain to metabolize human milk oligosaccharides into acetate. This study demonstrates that microbiota supplementation is associated with a Bifidobacterium -dominated preterm microbiota and gastrointestinal environment more closely resembling that of full-term infants.
Accurate classification of a microbial mock community using MinION sequencing. We benchmarked MinION technology by profiling a bacterial mock community using R7.3 flow cells. Reads were analysed with NanoOK 18 and produced alignments to the 20 microbial reference sequences with 82-89% identity 19. Coverage ranged from almost 0 × (8 reads) of Actinomyces odontolyticus to 13 × (7,695 reads) of Streptococcus mutans, which is consistent with expected mock concentrations (Supplementary Table 1). Benchmarking to Illumina sequencing demonstrated high correlation with expected proportions (Fig. 1a, log-transformed Pearson's r = 0.94 for MinION and 0.97 for Illumina), and with each other (log-transformed Pearson's r = 0.98). Broadly similar abundance levels across both platforms were observed, with some differences in assignment to species versus genus/family (Fig. 1b). This is probable since the longer length Nanopore reads should provide
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