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Gut microbiota composition during hospitalization is associated with 60-day mortality after severe COVID-19

BACKGROUND: Gut microbiota alterations have been reported in hospitalized COVID-19 patients, with reduced alpha diversity and altered microbiota composition related to respiratory failure. However, data regarding gut microbiota and mortality are scarce. METHODS: Rectal swabs for gut microbiota analy...

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Autores principales: Trøseid, Marius, Holter, Jan Cato, Holm, Kristian, Vestad, Beate, Sazonova, Taisiia, Granerud, Beathe K., Dyrhol-Riise, Anne Ma, Holten, Aleksander R., Tonby, Kristian, Kildal, Anders Benjamin, Heggelund, Lars, Tveita, Anders, Bøe, Simen, Müller, Karl Erik, Jenum, Synne, Hov, Johannes R., Ueland, Thor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9946863/
https://www.ncbi.nlm.nih.gov/pubmed/36814280
http://dx.doi.org/10.1186/s13054-023-04356-2
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author Trøseid, Marius
Holter, Jan Cato
Holm, Kristian
Vestad, Beate
Sazonova, Taisiia
Granerud, Beathe K.
Dyrhol-Riise, Anne Ma
Holten, Aleksander R.
Tonby, Kristian
Kildal, Anders Benjamin
Heggelund, Lars
Tveita, Anders
Bøe, Simen
Müller, Karl Erik
Jenum, Synne
Hov, Johannes R.
Ueland, Thor
author_facet Trøseid, Marius
Holter, Jan Cato
Holm, Kristian
Vestad, Beate
Sazonova, Taisiia
Granerud, Beathe K.
Dyrhol-Riise, Anne Ma
Holten, Aleksander R.
Tonby, Kristian
Kildal, Anders Benjamin
Heggelund, Lars
Tveita, Anders
Bøe, Simen
Müller, Karl Erik
Jenum, Synne
Hov, Johannes R.
Ueland, Thor
author_sort Trøseid, Marius
collection PubMed
description BACKGROUND: Gut microbiota alterations have been reported in hospitalized COVID-19 patients, with reduced alpha diversity and altered microbiota composition related to respiratory failure. However, data regarding gut microbiota and mortality are scarce. METHODS: Rectal swabs for gut microbiota analyses were collected within 48 h after hospital admission (baseline; n = 123) and three-month post-admission (n = 50) in a subset of patients included in the Norwegian SARS-CoV2 cohort study. Samples were analysed by sequencing the 16S rRNA gene. Gut microbiota diversity and composition at baseline were assessed in relation to need for intensive care unit (ICU) admission during hospitalization. The primary objective was to investigate whether the ICU-related gut microbiota was associated with 60-day mortality. RESULTS: Gut microbiota diversity (Shannon index) at baseline was lower in COVID-19 patients requiring ICU admission during hospitalization than in those managed in general wards. A dysbiosis index representing a balance of enriched and reduced taxa in ICU compared with ward patients, including decreased abundance of butyrate-producing microbes and enrichment of a partly oral bacterial flora, was associated with need of ICU admission independent of antibiotic use, dexamethasone use, chronic pulmonary disease, PO(2)/FiO(2) ratio, C-reactive protein, neutrophil counts or creatinine levels (adjusted p < 0.001). The ICU-related dysbiosis index at baseline correlated with systemic inflammation and was associated with 60-day mortality in univariate analyses (Hazard ratio 3.70 [2.00–8.6], p < 0.001), as well as after separate adjustment for covariates. At the three-month follow-up, the dysbiosis index remained elevated in ICU patients compared with ward patients (adjusted p = 0.007). CONCLUSIONS: Although our data should be regarded as exploratory due to low number of clinical end points, they suggest that gut microbiota alterations during hospitalization could be related to poor prognosis after severe COVID-19. Larger studies of gut involvement during COVID-19 in relation to long-term clinical outcome are warranted. Trial registration NCT04381819. Retrospectively registered May 11, 2020. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13054-023-04356-2.
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spelling pubmed-99468632023-02-23 Gut microbiota composition during hospitalization is associated with 60-day mortality after severe COVID-19 Trøseid, Marius Holter, Jan Cato Holm, Kristian Vestad, Beate Sazonova, Taisiia Granerud, Beathe K. Dyrhol-Riise, Anne Ma Holten, Aleksander R. Tonby, Kristian Kildal, Anders Benjamin Heggelund, Lars Tveita, Anders Bøe, Simen Müller, Karl Erik Jenum, Synne Hov, Johannes R. Ueland, Thor Crit Care Research BACKGROUND: Gut microbiota alterations have been reported in hospitalized COVID-19 patients, with reduced alpha diversity and altered microbiota composition related to respiratory failure. However, data regarding gut microbiota and mortality are scarce. METHODS: Rectal swabs for gut microbiota analyses were collected within 48 h after hospital admission (baseline; n = 123) and three-month post-admission (n = 50) in a subset of patients included in the Norwegian SARS-CoV2 cohort study. Samples were analysed by sequencing the 16S rRNA gene. Gut microbiota diversity and composition at baseline were assessed in relation to need for intensive care unit (ICU) admission during hospitalization. The primary objective was to investigate whether the ICU-related gut microbiota was associated with 60-day mortality. RESULTS: Gut microbiota diversity (Shannon index) at baseline was lower in COVID-19 patients requiring ICU admission during hospitalization than in those managed in general wards. A dysbiosis index representing a balance of enriched and reduced taxa in ICU compared with ward patients, including decreased abundance of butyrate-producing microbes and enrichment of a partly oral bacterial flora, was associated with need of ICU admission independent of antibiotic use, dexamethasone use, chronic pulmonary disease, PO(2)/FiO(2) ratio, C-reactive protein, neutrophil counts or creatinine levels (adjusted p < 0.001). The ICU-related dysbiosis index at baseline correlated with systemic inflammation and was associated with 60-day mortality in univariate analyses (Hazard ratio 3.70 [2.00–8.6], p < 0.001), as well as after separate adjustment for covariates. At the three-month follow-up, the dysbiosis index remained elevated in ICU patients compared with ward patients (adjusted p = 0.007). CONCLUSIONS: Although our data should be regarded as exploratory due to low number of clinical end points, they suggest that gut microbiota alterations during hospitalization could be related to poor prognosis after severe COVID-19. Larger studies of gut involvement during COVID-19 in relation to long-term clinical outcome are warranted. Trial registration NCT04381819. Retrospectively registered May 11, 2020. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13054-023-04356-2. BioMed Central 2023-02-23 /pmc/articles/PMC9946863/ /pubmed/36814280 http://dx.doi.org/10.1186/s13054-023-04356-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, 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 changes were made. 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/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Trøseid, Marius
Holter, Jan Cato
Holm, Kristian
Vestad, Beate
Sazonova, Taisiia
Granerud, Beathe K.
Dyrhol-Riise, Anne Ma
Holten, Aleksander R.
Tonby, Kristian
Kildal, Anders Benjamin
Heggelund, Lars
Tveita, Anders
Bøe, Simen
Müller, Karl Erik
Jenum, Synne
Hov, Johannes R.
Ueland, Thor
Gut microbiota composition during hospitalization is associated with 60-day mortality after severe COVID-19
title Gut microbiota composition during hospitalization is associated with 60-day mortality after severe COVID-19
title_full Gut microbiota composition during hospitalization is associated with 60-day mortality after severe COVID-19
title_fullStr Gut microbiota composition during hospitalization is associated with 60-day mortality after severe COVID-19
title_full_unstemmed Gut microbiota composition during hospitalization is associated with 60-day mortality after severe COVID-19
title_short Gut microbiota composition during hospitalization is associated with 60-day mortality after severe COVID-19
title_sort gut microbiota composition during hospitalization is associated with 60-day mortality after severe covid-19
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9946863/
https://www.ncbi.nlm.nih.gov/pubmed/36814280
http://dx.doi.org/10.1186/s13054-023-04356-2
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