A reconceptualized framework for human microbiome transmission in early life

Seth Rakoff-Nahoum (), Justine Debelius, Mireia Valles-Colomer, Hanna Theodora Noordzij, Maria Esteban-Torres, Alexandra Zhernakova, Nele Brusselaers and Veronika Kuchařová Pettersen ()
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Seth Rakoff-Nahoum: Boston Children’s Hospital
Justine Debelius: Johns Hopkins Bloomberg School of Public Health
Mireia Valles-Colomer: Universitat Pompeu Fabra
Hanna Theodora Noordzij: University of Oslo
Maria Esteban-Torres: Institute of Agrochemistry and Food Technology- Spanish National Research Council (IATA-CSIC)
Alexandra Zhernakova: University Medical Center Groningen
Nele Brusselaers: University of Antwerp
Veronika Kuchařová Pettersen: UiT The Arctic University of Norway

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Human development and physiology are fundamentally linked with the microbiome. This is particularly true during early life, a critical period for microbiome assembly and its impact on the host. Understanding microbial acquisition in early life is thus central to both our basic understanding of the human microbiome and strategies for disease prevention and treatment. Here, we review the historical approaches to categorize microbial transmission originating from the fields of infectious disease epidemiology and evolutionary biology and discuss how this lexicon has influenced our approach to studying the early-life microbiome, often leading to confusion and misinterpretation. We then present a conceptual framework to capture the multifaceted nature of human microbiome acquisition based on four key components: what, where, who, and when. We present ways these parameters may be assigned, with a particular focus on the ‘transmitted strain’ through metagenomics to capture these elements. We end with a discussion of approaches for implementing this framework toward defining each component of microbiome acquisition.

Date: 2025
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DOI: 10.1038/s41467-025-61998-2

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