{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T22:23:43Z","timestamp":1767911023464,"version":"3.49.0"},"reference-count":173,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T00:00:00Z","timestamp":1663113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["CEECIND\/02373\/2020"],"award-info":[{"award-number":["CEECIND\/02373\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Alteration in gut microbiota has been associated with COVID-19. However, the underlying mechanisms remain poorly understood. Here, we outlined three potential interconnected mechanistic pathways leading to gut dysbiosis as an adverse outcome following SARS-CoV-2 presence in the gastrointestinal tract. Evidence from the literature and current uncertainties are reported for each step of the different pathways. One pathway investigates evidence that intestinal infection by SARS-CoV-2 inducing intestinal inflammation alters the gut microbiota. Another pathway links the binding of viral S protein to angiotensin-converting enzyme 2 (ACE2) to the dysregulation of this receptor, essential in intestinal homeostasis\u2014notably for amino acid metabolism\u2014leading to gut dysbiosis. Additionally, SARS-CoV-2 could induce gut dysbiosis by infecting intestinal bacteria. Assessing current evidence within the Adverse Outcome Pathway framework justifies confidence in the proposed mechanisms to support disease management and permits the identification of inconsistencies and knowledge gaps to orient further research.<\/jats:p>","DOI":"10.3390\/jcm11185400","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T23:16:36Z","timestamp":1663197396000},"page":"5400","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Mechanisms Leading to Gut Dysbiosis in COVID-19: Current Evidence and Uncertainties Based on Adverse Outcome Pathways"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2707-482X","authenticated-orcid":false,"given":"Laure-Alix","family":"Clerbaux","sequence":"first","affiliation":[{"name":"European Commission, Joint Research Centre (JRC), 21027 Ispra, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7395-214X","authenticated-orcid":false,"given":"Julija","family":"Filipovska","sequence":"additional","affiliation":[{"name":"Independent Researcher, 6000 Ohrid, North Macedonia"}]},{"given":"Amalia","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"European Commission, Joint Research Centre (JRC), 2440 Geel, Belgium"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6782-4704","authenticated-orcid":false,"given":"Mauro","family":"Petrillo","sequence":"additional","affiliation":[{"name":"Seidor Italy SRL, 20219 Milano, Italy"}]},{"given":"Sandra","family":"Coecke","sequence":"additional","affiliation":[{"name":"European Commission, Joint Research Centre (JRC), 21027 Ispra, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4129-6659","authenticated-orcid":false,"given":"Maria-Joao","family":"Amorim","sequence":"additional","affiliation":[{"name":"Instituto Gulbenkian de Ci\u00eancia, 2780-156 Oerias, Portugal"},{"name":"Cat\u00f3lica Medical School, Cat\u00f3lica Biomedical Research Centre, Universidade Cat\u00f3lica Portuguesa, 1649-023 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5560-1717","authenticated-orcid":false,"given":"Lucia","family":"Grenga","sequence":"additional","affiliation":[{"name":"D\u00e9partement M\u00e9dicaments et Technologies pour la Sant\u00e9, Commissariat \u00e0 l\u2019\u00c9nergie Atomique et Aux \u00c9nergies Alternatives (CEA), Institut National de Recherche pour l\u2019Agriculture, l\u2019Alimentation et l\u2019Environnement (INRAE), Universit\u00e9 Paris-Saclay, 30200 Bagnols-sur-C\u00e8ze, France"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/s41586-020-2521-4","article-title":"Factors associated with COVID-19-related death using OpenSAFELY","volume":"584","author":"Williamson","year":"2020","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Chidambaram, V., Tun, N.L., Haque, W.Z., Majella, M.G., Sivakumar, R.K., Kumar, A., Hsu, A.T.-W., Ishak, I.A., Nur, A.A., and Ayeh, S.K. 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