Modulating the developing gut microbiota with 2fucosyllactose and pooled human milk oligosaccharides

Background:Synthetic human milk oligosaccharide (HMO) structures, such as 2fucosyllactose (2FL), are being used to supplement commercially available infant formula, despite limited research into their impact on the child gut microbiota. As such, this study sought to investigate the impact of 4 g/L pooled HMOs (pHMOs) and 0.5 g/L 2FL on the composition and activity of microbial communities derived from the stool of seven infant donors. Furthermore, 330 bacterial isolates, spanning 157 species, were isolated from the aforementioned microbial communities and evaluable for their ability to metabolize HMOs in monocultures.Results:16S rRNA sequencing demonstrated significant shifts in the composition of the communities when treated with pHMOs, including increased absolute abundance of several genera, notably Bacteroides. Communities also increased production of health-associated metabolites, such as acetate, as measured by NMR-based metabolomics, when exposed to pHMOs. In contrast, 2FL continuously yielded results similar to the control. Monoculture treatment of the bacterial isolates with pHMOs revealed the enhanced growth of members of 101 non-Bifidobacterium species. Finally, a high degree of intraspecies variation was observed in the ability to metabolize HMOs.Conclusion:Our study highlights the considerable inter-individual variability in the ability to derive health benefits from exogenously administered HMOs. By analyzing HMO usage in a large gut bacteria collection, we have demonstrated that HMOs interact with wide diversity of non-Bifidobacterium species. Overall, this study has considerably expanded our knowledge of HMO/gut microbiota interactions and has provided deeper insights into early life dietary supplementation with HMOs.