Temporal dynamics and microbial interactions shaping the gut resistome in early infancy

Ioanna Chatzigiannidou, Pi L. Johansen, Rasmus K. Dehli, Janne Marie Moll, Carsten Eriksen, Pernille N. Myers, Henrik M. Roager, Lili Yang, Jakob Stokholm, Søren J. Sørensen, Karen A. Krogfelt, Martin F. Laursen, Urvish Trivedi, Annika Scheynius, Karsten Kristiansen, Axel Mie, Johan Alm and Susanne Brix ()
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Ioanna Chatzigiannidou: Technical University of Denmark
Pi L. Johansen: Technical University of Denmark
Rasmus K. Dehli: Technical University of Denmark
Janne Marie Moll: Technical University of Denmark
Carsten Eriksen: Technical University of Denmark
Pernille N. Myers: Technical University of Denmark
Henrik M. Roager: University of Copenhagen
Lili Yang: University of Copenhagen
Jakob Stokholm: University of Copenhagen
Søren J. Sørensen: University of Copenhagen
Karen A. Krogfelt: Statens Serum Institut
Martin F. Laursen: Technical University of Denmark
Urvish Trivedi: University of Copenhagen
Annika Scheynius: Södersjukhuset
Karsten Kristiansen: University of Copenhagen
Axel Mie: Södersjukhuset
Johan Alm: Södersjukhuset
Susanne Brix: Technical University of Denmark

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract Despite the critical role of the gut resistome in spreading of antimicrobial resistance (AMR), strategies to reduce the abundance of antibiotic resistance genes (ARGs) during microbiota development in infancy remain underexplored. Using longitudinal quantitative metagenomic data, we here show that ARGs are present in the gut microbiota from the first week of life, with a peak in absolute ARG abundance and richness at 6 months. Delivery mode significantly affects early ARG dynamics, and vaginally delivered infants exhibit higher ARG abundance due to maternal transmission of Escherichia coli strains harbouring extensive resistance repertoires. The abundance of E. coli and other ARG-rich taxa inversely correlates with aromatic lactic acid-producing bifidobacteria, and aromatic lactic acids strongly inhibit the in vitro growth of E. coli and other opportunistic ARG-rich taxa. Our results highlight temporal and critical microbial interactions shaping the gut resistome in early infancy, pointing to potential interventions to curb AMR during this vulnerable developmental window by promoting colonization of aromatic lactic acid-producing bifidobacteria.

Date: 2025
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DOI: 10.1038/s41467-025-63401-6

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