eprintid: 10160371 rev_number: 7 eprint_status: archive userid: 699 dir: disk0/10/16/03/71 datestamp: 2022-11-25 17:19:55 lastmod: 2022-11-25 17:19:55 status_changed: 2022-11-25 17:19:55 type: article metadata_visibility: show sword_depositor: 699 creators_name: Lymberopoulos, Eva creators_name: Gentili, Giorgia Isabella creators_name: Budhdeo, Sanjay creators_name: Sharma, Nikhil title: COVID-19 severity is associated with population-level gut microbiome variations ispublished: pub divisions: UCL divisions: B02 divisions: C07 divisions: D07 divisions: F84 keywords: gut microbiome, COVID-19, population health, topological data analysis, probiotics note: Copyright © 2022 Lymberopoulos, Gentili, Budhdeo and Sharma. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. abstract: The human gut microbiome interacts with many diseases, with recent small studies suggesting a link with COVID-19 severity. Exploring this association at the population-level may provide novel insights and help to explain differences in COVID-19 severity between countries. We explore whether there is an association between the gut microbiome of people within different countries and the severity of COVID-19, measured as hospitalisation rate. We use data from the large (n = 3,055) open-access gut microbiome repository curatedMetagenomicData, as well as demographic and country-level metadata. Twelve countries were placed into two groups (high/low) according to COVID-19 hospitalisation rate before December 2020 (ourworldindata.com). We use an unsupervised machine learning method, Topological Data Analysis (TDA). This method analyses both the local geometry and global topology of a high-dimensional dataset, making it particularly suitable for population-level microbiome data. We report an association of distinct baseline population-level gut microbiome signatures with COVID-19 severity. This was found both with a PERMANOVA, as well as with TDA. Specifically, it suggests an association of anti-inflammatory bacteria, including Bifidobacteria species and Eubacterium rectale, with lower severity, and pro-inflammatory bacteria such as Prevotella copri with higher severity. This study also reports a significant impact of country-level confounders, specifically of the proportion of over 70-year-olds in the population, GDP, and human development index. Further interventional studies should examine whether these relationships are causal, as well as considering the contribution of other variables such as genetics, lifestyle, policy, and healthcare system. The results of this study support the value of a population-level association design in microbiome research in general and for the microbiome-COVID-19 relationship, in particular. Finally, this research underscores the potential of TDA for microbiome studies, and in identifying novel associations. date: 2022-08-23 date_type: published publisher: FRONTIERS MEDIA SA official_url: https://doi.org/10.3389/fcimb.2022.963338 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1982370 doi: 10.3389/fcimb.2022.963338 medium: Electronic-eCollection lyricists_name: Budhdeo, Sanjay lyricists_id: SBUDH52 actors_name: Flynn, Bernadette actors_id: BFFLY94 actors_role: owner funding_acknowledgements: [Reta Lila Weston Trust]; EP/S021612/1 [~EPSRC]; 566701 [Wellcome Trust]; [National Institute for Health Research University College London Hospitals Biomedical Research Centre] full_text_status: public publication: Frontiers in Cellular and Infection Microbiology volume: 12 article_number: 963338 pages: 17 event_location: Switzerland issn: 2235-2988 citation: Lymberopoulos, Eva; Gentili, Giorgia Isabella; Budhdeo, Sanjay; Sharma, Nikhil; (2022) COVID-19 severity is associated with population-level gut microbiome variations. Frontiers in Cellular and Infection Microbiology , 12 , Article 963338. 10.3389/fcimb.2022.963338 <https://doi.org/10.3389/fcimb.2022.963338>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10160371/1/fcimb-12-963338.pdf