Integrative metagenomics and metabolomics reveal age-associated gut microbiota and metabolite alterations in a hamster model of COVID-19

Aging is a key contributor of morbidity and mortality during acute viral pneumonia. The potential role of age-associated dysbiosis on disease outcomes is still elusive. In the current study, we used high-resolution shotgun metagenomics and targeted metabolomics to characterize SARS-CoV-2-associated...

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Main Authors: Patrícia Brito Rodrigues, Vinícius de Rezende Rodovalho, Valentin Sencio, Nicolas Benech, Marybeth Creskey, Fabiola Silva Angulo, Lou Delval, Cyril Robil, Philippe Gosset, Arnaud Machelart, Joel Haas, Amandine Descat, Jean François Goosens, Delphine Beury, Florence Maurier, David Hot, Isabelle Wolowczuk, Harry Sokol, Xu Zhang, Marco Aurélio Ramirez Vinolo, François Trottein
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Gut Microbes
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Online Access:https://www.tandfonline.com/doi/10.1080/19490976.2025.2486511
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author Patrícia Brito Rodrigues
Vinícius de Rezende Rodovalho
Valentin Sencio
Nicolas Benech
Marybeth Creskey
Fabiola Silva Angulo
Lou Delval
Cyril Robil
Philippe Gosset
Arnaud Machelart
Joel Haas
Amandine Descat
Jean François Goosens
Delphine Beury
Florence Maurier
David Hot
Isabelle Wolowczuk
Harry Sokol
Xu Zhang
Marco Aurélio Ramirez Vinolo
François Trottein
author_facet Patrícia Brito Rodrigues
Vinícius de Rezende Rodovalho
Valentin Sencio
Nicolas Benech
Marybeth Creskey
Fabiola Silva Angulo
Lou Delval
Cyril Robil
Philippe Gosset
Arnaud Machelart
Joel Haas
Amandine Descat
Jean François Goosens
Delphine Beury
Florence Maurier
David Hot
Isabelle Wolowczuk
Harry Sokol
Xu Zhang
Marco Aurélio Ramirez Vinolo
François Trottein
author_sort Patrícia Brito Rodrigues
collection DOAJ
description Aging is a key contributor of morbidity and mortality during acute viral pneumonia. The potential role of age-associated dysbiosis on disease outcomes is still elusive. In the current study, we used high-resolution shotgun metagenomics and targeted metabolomics to characterize SARS-CoV-2-associated changes in the gut microbiota from young (2-month-old) and aged (22-month-old) hamsters, a valuable model of COVID-19. We show that age-related dysfunctions in the gut microbiota are linked to disease severity and long-term sequelae in older hamsters. Our data also reveal age-specific changes in the composition and metabolic activity of the gut microbiota during both the acute phase (day 7 post-infection, D7) and the recovery phase (D22) of infection. Aged hamsters exhibited the most notable shifts in gut microbiota composition and plasma metabolic profiles. Through an integrative analysis of metagenomics, metabolomics, and clinical data, we identified significant associations between bacterial taxa, metabolites and disease markers in the aged group. On D7 (high viral load and lung epithelial damage) and D22 (body weight loss and fibrosis), numerous amino acids, amino acid-related molecules, and indole derivatives were found to correlate with disease markers. In particular, a persistent decrease in phenylalanine, tryptophan, glutamic acid, and indoleacetic acid in aged animals positively correlated with poor recovery of body weight and/or lung fibrosis by D22. In younger hamsters, several bacterial taxa (Eubacterium, Oscillospiraceae, Lawsonibacter) and plasma metabolites (carnosine and cis-aconitic acid) were associated with mild disease outcomes. These findings support the need for age-specific microbiome-targeting strategies to more effectively manage acute viral pneumonia and long-term disease outcomes.
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spelling doaj-art-fb677420f21c4b4eb1a6f2ae110e59de2025-08-20T03:06:17ZengTaylor & Francis GroupGut Microbes1949-09761949-09842025-12-0117110.1080/19490976.2025.2486511Integrative metagenomics and metabolomics reveal age-associated gut microbiota and metabolite alterations in a hamster model of COVID-19Patrícia Brito Rodrigues0Vinícius de Rezende Rodovalho1Valentin Sencio2Nicolas Benech3Marybeth Creskey4Fabiola Silva Angulo5Lou Delval6Cyril Robil7Philippe Gosset8Arnaud Machelart9Joel Haas10Amandine Descat11Jean François Goosens12Delphine Beury13Florence Maurier14David Hot15Isabelle Wolowczuk16Harry Sokol17Xu Zhang18Marco Aurélio Ramirez Vinolo19François Trottein20U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, FranceLaboratory of Immunoinflammation, Institute of Biology, University of Campinas (UNICAMP), Campinas, BrazilU1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, FranceGastroenterology Department, Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Saint Antoine Hospital, Paris, FranceRegulatory Research Division, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada, University of Ottawa, Ottawa, CanadaU1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, FranceU1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, FranceU1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, FranceU1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, FranceU1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, FranceU1011-EGID, University of Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, FranceEA 7365 - GRITA - Groupe de Recherche sur les formes Injectables et les Technologies Associées, University of Lille, CHU Lille, Lille, FranceEA 7365 - GRITA - Groupe de Recherche sur les formes Injectables et les Technologies Associées, University of Lille, CHU Lille, Lille, FranceUS 41 - UAR 2014 - PLBS, University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, FranceUS 41 - UAR 2014 - PLBS, University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, FranceUS 41 - UAR 2014 - PLBS, University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, FranceU1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, FranceGastroenterology Department, Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Saint Antoine Hospital, Paris, FranceRegulatory Research Division, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada, University of Ottawa, Ottawa, CanadaLaboratory of Immunoinflammation, Institute of Biology, University of Campinas (UNICAMP), Campinas, BrazilU1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, FranceAging is a key contributor of morbidity and mortality during acute viral pneumonia. The potential role of age-associated dysbiosis on disease outcomes is still elusive. In the current study, we used high-resolution shotgun metagenomics and targeted metabolomics to characterize SARS-CoV-2-associated changes in the gut microbiota from young (2-month-old) and aged (22-month-old) hamsters, a valuable model of COVID-19. We show that age-related dysfunctions in the gut microbiota are linked to disease severity and long-term sequelae in older hamsters. Our data also reveal age-specific changes in the composition and metabolic activity of the gut microbiota during both the acute phase (day 7 post-infection, D7) and the recovery phase (D22) of infection. Aged hamsters exhibited the most notable shifts in gut microbiota composition and plasma metabolic profiles. Through an integrative analysis of metagenomics, metabolomics, and clinical data, we identified significant associations between bacterial taxa, metabolites and disease markers in the aged group. On D7 (high viral load and lung epithelial damage) and D22 (body weight loss and fibrosis), numerous amino acids, amino acid-related molecules, and indole derivatives were found to correlate with disease markers. In particular, a persistent decrease in phenylalanine, tryptophan, glutamic acid, and indoleacetic acid in aged animals positively correlated with poor recovery of body weight and/or lung fibrosis by D22. In younger hamsters, several bacterial taxa (Eubacterium, Oscillospiraceae, Lawsonibacter) and plasma metabolites (carnosine and cis-aconitic acid) were associated with mild disease outcomes. These findings support the need for age-specific microbiome-targeting strategies to more effectively manage acute viral pneumonia and long-term disease outcomes.https://www.tandfonline.com/doi/10.1080/19490976.2025.2486511Viral pneumoniaSARS-CoV-2gut microbiotaagingmetagenomicsmetabolomics
spellingShingle Patrícia Brito Rodrigues
Vinícius de Rezende Rodovalho
Valentin Sencio
Nicolas Benech
Marybeth Creskey
Fabiola Silva Angulo
Lou Delval
Cyril Robil
Philippe Gosset
Arnaud Machelart
Joel Haas
Amandine Descat
Jean François Goosens
Delphine Beury
Florence Maurier
David Hot
Isabelle Wolowczuk
Harry Sokol
Xu Zhang
Marco Aurélio Ramirez Vinolo
François Trottein
Integrative metagenomics and metabolomics reveal age-associated gut microbiota and metabolite alterations in a hamster model of COVID-19
Gut Microbes
Viral pneumonia
SARS-CoV-2
gut microbiota
aging
metagenomics
metabolomics
title Integrative metagenomics and metabolomics reveal age-associated gut microbiota and metabolite alterations in a hamster model of COVID-19
title_full Integrative metagenomics and metabolomics reveal age-associated gut microbiota and metabolite alterations in a hamster model of COVID-19
title_fullStr Integrative metagenomics and metabolomics reveal age-associated gut microbiota and metabolite alterations in a hamster model of COVID-19
title_full_unstemmed Integrative metagenomics and metabolomics reveal age-associated gut microbiota and metabolite alterations in a hamster model of COVID-19
title_short Integrative metagenomics and metabolomics reveal age-associated gut microbiota and metabolite alterations in a hamster model of COVID-19
title_sort integrative metagenomics and metabolomics reveal age associated gut microbiota and metabolite alterations in a hamster model of covid 19
topic Viral pneumonia
SARS-CoV-2
gut microbiota
aging
metagenomics
metabolomics
url https://www.tandfonline.com/doi/10.1080/19490976.2025.2486511
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