Rakoff-Nahoum, SethDebelius, JustineVallès Colomer, MireiaNoordzij, Hanna TheodoraEsteban-Torres, MaríaZhernakova, AlexandraBrusselaers, NelePettersen, Veronika Kuchařová2025-11-102025-11-102025Rakoff-Nahoum S, Debelius J, Valles-Colomer M, Noordzij HT, Esteban-Torres M, Zhernakova A, Brusselaers N, Pettersen VK. A reconceptualized framework for human microbiome transmission in early life. Nat Commun. 2025 Aug 14;16(1):7546. DOI: 10.1038/s41467-025-61998-22041-1723http://hdl.handle.net/10230/71835Human 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.application/pdfeng© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.info:eu-repo/semantics/article2025-11-10http://dx.doi.org/10.1038/s41467-025-61998-2Microbial ecologyMicrobiomeinfo:eu-repo/semantics/openAccess