Human milk oligosaccharide mediates mutualism between Escherichia coli and Bifidobacterium bifidum

Seki, David, Pollak, Shaul, Kujawska, Magdalena, Kiu, Raymond, Acuna-Gonzalez, Antia, Crouch, Lucy I., Bakshani, Cassie R., Chivers, Peter T., Mommers, Monique, van Best, Nils, Penders, John and Hall, Lindsay J. (2026) Human milk oligosaccharide mediates mutualism between Escherichia coli and Bifidobacterium bifidum. Nature Communications, 17 (1). ISSN 2041-1723

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Abstract

Infant gut microbiota development involves frequent colonization by Enterobacteriaceae, particularly Escherichia coli, yet their ecological role in healthy infants is unclear. Here, we analyse longitudinal stool samples from healthy, term-born, breastfed infants (n = 41) and related mothers (n = 30) using shotgun metagenomics and novel computational approaches. Strain-resolved profiling indicates that Bifidobacterium species are frequently shared within families, whereas E. coli derive from external sources, but often persist within individuals. Despite differing ecological strategies, these genera co-exist and share evolutionary adaptations related to lactose acquisition in the infant gut. In vitro, we demonstrate that interactions between E. coli and Bifidobacterium bifidum are mutualistic in co-culture, where E. coli supplies cysteine to its auxotrophic partner, facilitating cooperative degradation of 2′-fucosyllactose, the predominant human milk oligosaccharide. In turn, the liberated monosaccharides sustain E. coli growth, highlighting a cooperative cross-feeding interaction that may contribute to regulating E. coli abundance within the infant host.

Item Type: Article
Additional Information: Data availability: Source data are provided with this paper. Further information for resources and reagents should be directed to and will be fulfilled by lead contacts David Seki (david.seki@univie.ac.at) or Lindsay J. Hall (l.hall.3@bham.ac.uk). Infant fecal sample metagenome sequencing raw reads are publicly available in the NCBI Sequence Read Archive (SRA) under accession no. PRJNA1230889. All 458 MAGs recovered from gut metagenome samples are available via Zenodo108 (https://doi.org/10.5281/zenodo.18848062), and all high-quality MAGs with completeness > 95% (n = 279) are also available via PRJNA1230889. Source data are provided with this paper. Code availability: The code for analysis of the data109 can be accessed via https://github.com/sekid666/MAJIC and https://doi.org/10.5281/zenodo.18833415.
Uncontrolled Keywords: general chemistry,general biochemistry,genetics and molecular biology,general,general physics and astronomy,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1600/1600
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Depositing User: LivePure Connector
Date Deposited: 12 May 2026 13:33
Last Modified: 14 May 2026 15:16
URI: https://ueaeprints.uea.ac.uk/id/eprint/102963
DOI: 10.1038/s41467-026-71764-7

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