Sunjae Lee1,2,18, Theo Portlock3,18, Emmanuelle Le Chatelier4,18, Fernando Garcia-Guevara1,3,18, Frederick Clasen1, Florian Plaza Oñate4, Nicolas Pons4, Neelu Begum1, Azadeh Harzandi1, Ceri Proffitt1, Dorines Rosario1, Stefania Vaga1, Junseok Park5, Kalle von Feilitzen3, Fredric Johansson3, Cheng Zhang3, Lindsey A. Edwards1,6, Vincent Lombard7,8, Franck Gauthier4, Claire J. Steves9, David Gomez-Cabrero1,10,11, Bernard Henrissat12,13, Doheon Lee5, Lars Engstrand14, Debbie L. Shawcross6, Gordon Proctor1, Mathieu Almeida4, Jens Nielsen15,16, Adil Mardinoglu1,3, David L. Moyes1, Stanislav Dusko Ehrlich4,17, Mathias Uhlen3 and Saeed Shoaie1,3 1Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, SE1 9RT, United Kingdom; 2School of Life Sciences, Gwangju Institute of Science and Technology (GIST), 61005, Gwangju, Republic of Korea; 3Science for Life Laboratory, KTH–Royal Institute of Technology, Stockholm, SE-171 21, Sweden; 4University Paris-Saclay, INRAE, MetaGenoPolis, 78350 Jouy-en-Josas, France; 5Department of Bio and Brain Engineering, KAIST, Yuseong-gu, Daejeon 305-701, Republic of Korea; 6Institute of Liver Studies, Department of Inflammation Biology, School of Immunology and Microbial Sciences, King's College London, London SE5 9NU, United Kingdom; 7INRAE, USC1408 Architecture et Fonction des Macromolécules Biologiques (AFMB), Marseille 13288, France; 8Architecture et Fonction des Macromolécules Biologiques (AFMB), CNRS, Aix-Marseille University, Marseille 13288, France; 9Department of Twin Research & Genetic Epidemiology, King's College London, London WC2R 2LS, United Kingdom; 10Translational Bioinformatics Unit, Navarrabiomed, Universidad Pública de Navarra (UPNA), IdiSNA, 31008 Pamplona, Spain; 11Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia; 12Department of Biological Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia; 13Department of Biotechnology and Biomedicine, Technical University of Denmark, DK-2800 Lyngby, Denmark; 14Centre for Translational Microbiome Research (CTMR), Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet, 171 65 Stockholm, Sweden; 15Department of Biology and Biological Engineering, Chalmers University of Technology, SE-412 96 Gothenburg, Sweden; 16BioInnovation Institute, DK-2200 Copenhagen N, Denmark; 17Department of Clinical and Movement Neurosciences, University College London, London NW3 2PF, United Kingdom

↵18 These authors contributed equally to this work.

Corresponding authors: mathias.uhlenscilifelab.se, saeed.shoaiekcl.ac.uk Abstract

The human gut microbiota is of increasing interest, with metagenomics a key tool for analyzing bacterial diversity and functionality in health and disease. Despite increasing efforts to expand microbial gene catalogs and an increasing number of metagenome-assembled genomes, there have been few pan-metagenomic association studies and in-depth functional analyses across different geographies and diseases. Here, we explored 6014 human gut metagenome samples across 19 countries and 23 diseases by performing compositional, functional cluster, and integrative analyses. Using interpreted machine learning classification models and statistical methods, we identified Fusobacterium nucleatum and Anaerostipes hadrus with the highest frequencies, enriched and depleted, respectively, across different disease cohorts. Distinct functional distributions were observed in the gut microbiomes of both westernized and nonwesternized populations. These compositional and functional analyses are presented in the open-access Human Gut Microbiome Atlas, allowing for the exploration of the richness, disease, and regional signatures of the gut microbiota across different cohorts.

Footnotes

[Supplemental material is available for this article.]

Article published online before print. Article, supplemental material, and publication date are at https://www.genome.org/cgi/doi/10.1101/gr.278637.123.

Freely available online through the Genome Research Open Access option.

Received October 19, 2023. Accepted June 5, 2024.