Alteration of the gut microbiota’s composition and metabolic output correlates with COVID-19-like severity in obese NASH hamsters

Obese patientss with nonalcoholic steatohepatitis (NASH) are particularly prone to developing severe forms of coronavirus disease 19 (COVID-19). The gut-to-lung axis is critical during viral infections of the respiratory tract, and a change in the gut microbiota’s composition might have a critical r...

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Main Authors: Valentin Sencio, Nicolas Benech, Cyril Robil, Lucie Deruyter, Séverine Heumel, Arnaud Machelart, Thierry Sulpice, Antonin Lamazière, Corinne Grangette, François Briand, Harry Sokol, François Trottein
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Language:English
Published: Taylor & Francis Group 2022-12-01
Series:Gut Microbes
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Online Access:https://www.tandfonline.com/doi/10.1080/19490976.2022.2100200
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author Valentin Sencio
Nicolas Benech
Cyril Robil
Lucie Deruyter
Séverine Heumel
Arnaud Machelart
Thierry Sulpice
Antonin Lamazière
Corinne Grangette
François Briand
Harry Sokol
François Trottein
author_facet Valentin Sencio
Nicolas Benech
Cyril Robil
Lucie Deruyter
Séverine Heumel
Arnaud Machelart
Thierry Sulpice
Antonin Lamazière
Corinne Grangette
François Briand
Harry Sokol
François Trottein
author_sort Valentin Sencio
collection DOAJ
description Obese patientss with nonalcoholic steatohepatitis (NASH) are particularly prone to developing severe forms of coronavirus disease 19 (COVID-19). The gut-to-lung axis is critical during viral infections of the respiratory tract, and a change in the gut microbiota’s composition might have a critical role in disease severity. Here, we investigated the consequences of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the gut microbiota in the context of obesity and NASH. To this end, we set up a nutritional model of obesity with dyslipidemia and NASH in the golden hamster, a relevant preclinical model of COVID-19. Relative to lean non-NASH controls, obese NASH hamsters develop severe inflammation of the lungs and liver. 16S rRNA gene profiling showed that depending on the diet, SARS-CoV-2 infection induced various changes in the gut microbiota’s composition. Changes were more prominent and transient at day 4 post-infection in lean animals, alterations still persisted at day 10 in obese NASH animals. A targeted, quantitative metabolomic analysis revealed changes in the gut microbiota’s metabolic output, some of which were diet-specific and regulated over time. Our results showed that specifically diet-associated taxa are correlated with disease parameters. Correlations between infection variables and diet-associated taxa highlighted a number of potentially protective or harmful bacteria in SARS-CoV-2-infected hamsters. In particular, some taxa in obese NASH hamsters (e.g. Blautia and Peptococcus) were associated with pro-inflammatory parameters in both the lungs and the liver. These taxon profiles and their association with specific disease markers suggest that microbial patterns might influence COVID-19 outcomes.
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spelling doaj-art-a5f3a88364964b48ab00ce67879bbede2025-08-20T03:05:35ZengTaylor & Francis GroupGut Microbes1949-09761949-09842022-12-0114110.1080/19490976.2022.2100200Alteration of the gut microbiota’s composition and metabolic output correlates with COVID-19-like severity in obese NASH hamstersValentin Sencio0Nicolas Benech1Cyril Robil2Lucie Deruyter3Séverine Heumel4Arnaud Machelart5Thierry Sulpice6Antonin Lamazière7Corinne Grangette8François Briand9Harry Sokol10François Trottein11CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Univ. Lille, CNRS, Inserm, Lille, FranceInstitut National de la Santé et de la Recherche Médicale (Inserm) U1019, Lille, FranceCHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Univ. Lille, CNRS, Inserm, Lille, FranceCHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Univ. Lille, CNRS, Inserm, Lille, FranceCHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Univ. Lille, CNRS, Inserm, Lille, FranceCHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Univ. Lille, CNRS, Inserm, Lille, FrancePhysiogenex, Escalquens, FranceInserm, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Saint Antoine Hospital, Gastroenterology department, Sorbonne Université, Paris, FranceCHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Univ. Lille, CNRS, Inserm, Lille, FrancePhysiogenex, Escalquens, FranceInserm, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Saint Antoine Hospital, Gastroenterology department, Sorbonne Université, Paris, FranceCHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Univ. Lille, CNRS, Inserm, Lille, FranceObese patientss with nonalcoholic steatohepatitis (NASH) are particularly prone to developing severe forms of coronavirus disease 19 (COVID-19). The gut-to-lung axis is critical during viral infections of the respiratory tract, and a change in the gut microbiota’s composition might have a critical role in disease severity. Here, we investigated the consequences of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the gut microbiota in the context of obesity and NASH. To this end, we set up a nutritional model of obesity with dyslipidemia and NASH in the golden hamster, a relevant preclinical model of COVID-19. Relative to lean non-NASH controls, obese NASH hamsters develop severe inflammation of the lungs and liver. 16S rRNA gene profiling showed that depending on the diet, SARS-CoV-2 infection induced various changes in the gut microbiota’s composition. Changes were more prominent and transient at day 4 post-infection in lean animals, alterations still persisted at day 10 in obese NASH animals. A targeted, quantitative metabolomic analysis revealed changes in the gut microbiota’s metabolic output, some of which were diet-specific and regulated over time. Our results showed that specifically diet-associated taxa are correlated with disease parameters. Correlations between infection variables and diet-associated taxa highlighted a number of potentially protective or harmful bacteria in SARS-CoV-2-infected hamsters. In particular, some taxa in obese NASH hamsters (e.g. Blautia and Peptococcus) were associated with pro-inflammatory parameters in both the lungs and the liver. These taxon profiles and their association with specific disease markers suggest that microbial patterns might influence COVID-19 outcomes.https://www.tandfonline.com/doi/10.1080/19490976.2022.2100200SARS-CoV-2hamstersgut microbiotaobesityNASHCOVID-19
spellingShingle Valentin Sencio
Nicolas Benech
Cyril Robil
Lucie Deruyter
Séverine Heumel
Arnaud Machelart
Thierry Sulpice
Antonin Lamazière
Corinne Grangette
François Briand
Harry Sokol
François Trottein
Alteration of the gut microbiota’s composition and metabolic output correlates with COVID-19-like severity in obese NASH hamsters
Gut Microbes
SARS-CoV-2
hamsters
gut microbiota
obesity
NASH
COVID-19
title Alteration of the gut microbiota’s composition and metabolic output correlates with COVID-19-like severity in obese NASH hamsters
title_full Alteration of the gut microbiota’s composition and metabolic output correlates with COVID-19-like severity in obese NASH hamsters
title_fullStr Alteration of the gut microbiota’s composition and metabolic output correlates with COVID-19-like severity in obese NASH hamsters
title_full_unstemmed Alteration of the gut microbiota’s composition and metabolic output correlates with COVID-19-like severity in obese NASH hamsters
title_short Alteration of the gut microbiota’s composition and metabolic output correlates with COVID-19-like severity in obese NASH hamsters
title_sort alteration of the gut microbiota s composition and metabolic output correlates with covid 19 like severity in obese nash hamsters
topic SARS-CoV-2
hamsters
gut microbiota
obesity
NASH
COVID-19
url https://www.tandfonline.com/doi/10.1080/19490976.2022.2100200
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