npj Biofilms and Microbiomes (Aug 2024)
Gut microbiota dysbiosis is associated with altered tryptophan metabolism and dysregulated inflammatory response in COVID-19
- Morgan Essex,
- Belén Millet Pascual-Leone,
- Ulrike Löber,
- Mathias Kuhring,
- Bowen Zhang,
- Ulrike Brüning,
- Raphaela Fritsche-Guenther,
- Marta Krzanowski,
- Facundo Fiocca Vernengo,
- Sophia Brumhard,
- Ivo Röwekamp,
- Agata Anna Bielecka,
- Till Robin Lesker,
- Emanuel Wyler,
- Markus Landthaler,
- Andrej Mantei,
- Christian Meisel,
- Sandra Caesar,
- Charlotte Thibeault,
- Victor M. Corman,
- Lajos Marko,
- Norbert Suttorp,
- Till Strowig,
- Florian Kurth,
- Leif E. Sander,
- Yang Li,
- Jennifer A. Kirwan,
- Sofia K. Forslund,
- Bastian Opitz
Affiliations
- Morgan Essex
- Experimental and Clinical Research Center (ECRC), a cooperation of the Max Delbrück Center and Charité–Universitätsmedizin
- Belén Millet Pascual-Leone
- Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charité–Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
- Ulrike Löber
- Experimental and Clinical Research Center (ECRC), a cooperation of the Max Delbrück Center and Charité–Universitätsmedizin
- Mathias Kuhring
- Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC)
- Bowen Zhang
- Department of Computational Biology for Individualized Infection Medicine, Center for Individualized Infection Medicine (CiiM), a joint venture between the Helmholtz-Center for Infection Research (HZI) and the Hannover Medical School (MHH)
- Ulrike Brüning
- Berlin Institute of Health (BIH) at Charité, BIH Metabolomics Platform
- Raphaela Fritsche-Guenther
- Berlin Institute of Health (BIH) at Charité, BIH Metabolomics Platform
- Marta Krzanowski
- Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charité–Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
- Facundo Fiocca Vernengo
- Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charité–Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
- Sophia Brumhard
- Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charité–Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
- Ivo Röwekamp
- Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charité–Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
- Agata Anna Bielecka
- Department of Microbial Immune Regulation, Helmholtz Center for Infection Research (HZI)
- Till Robin Lesker
- Department of Microbial Immune Regulation, Helmholtz Center for Infection Research (HZI)
- Emanuel Wyler
- Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC)
- Markus Landthaler
- Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC)
- Andrej Mantei
- Labor Berlin-Charité Vivantes GmbH
- Christian Meisel
- Labor Berlin-Charité Vivantes GmbH
- Sandra Caesar
- Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charité–Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
- Charlotte Thibeault
- Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charité–Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
- Victor M. Corman
- Labor Berlin-Charité Vivantes GmbH
- Lajos Marko
- Experimental and Clinical Research Center (ECRC), a cooperation of the Max Delbrück Center and Charité–Universitätsmedizin
- Norbert Suttorp
- Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charité–Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
- Till Strowig
- Department of Computational Biology for Individualized Infection Medicine, Center for Individualized Infection Medicine (CiiM), a joint venture between the Helmholtz-Center for Infection Research (HZI) and the Hannover Medical School (MHH)
- Florian Kurth
- Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charité–Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
- Leif E. Sander
- Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charité–Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
- Yang Li
- Department of Computational Biology for Individualized Infection Medicine, Center for Individualized Infection Medicine (CiiM), a joint venture between the Helmholtz-Center for Infection Research (HZI) and the Hannover Medical School (MHH)
- Jennifer A. Kirwan
- Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC)
- Sofia K. Forslund
- Experimental and Clinical Research Center (ECRC), a cooperation of the Max Delbrück Center and Charité–Universitätsmedizin
- Bastian Opitz
- Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charité–Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
- DOI
- https://doi.org/10.1038/s41522-024-00538-0
- Journal volume & issue
-
Vol. 10,
no. 1
pp. 1 – 15
Abstract
Abstract The clinical course of COVID-19 is variable and often unpredictable. To test the hypothesis that disease progression and inflammatory responses associate with alterations in the microbiome and metabolome, we analyzed metagenome, metabolome, cytokine, and transcriptome profiles of repeated samples from hospitalized COVID-19 patients and uninfected controls, and leveraged clinical information and post-hoc confounder analysis. Severe COVID-19 was associated with a depletion of beneficial intestinal microbes, whereas oropharyngeal microbiota disturbance was mainly linked to antibiotic use. COVID-19 severity was also associated with enhanced plasma concentrations of kynurenine and reduced levels of several other tryptophan metabolites, lysophosphatidylcholines, and secondary bile acids. Moreover, reduced concentrations of various tryptophan metabolites were associated with depletion of Faecalibacterium, and tryptophan decrease and kynurenine increase were linked to enhanced production of inflammatory cytokines. Collectively, our study identifies correlated microbiome and metabolome alterations as a potential contributor to inflammatory dysregulation in severe COVID-19.
