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Gut microbiota dysbiosis is associated with altered tryptophan metabolism and dysregulated inflammatory response in severe COVID-19
| Item Type: | Preprint |
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| Title: | Gut microbiota dysbiosis is associated with altered tryptophan metabolism and dysregulated inflammatory response in severe COVID-19 |
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| Creators Name: | Essex, M. and Pascual-Leone, B.M. and Löber, U. and Kuhring, M. and Zhang, B. and Bruening, U. and Fritsche-Guenther, R. and Krzanowski, M. and Vernengo, F.F. and Brumhard, S. and Röwekamp, I. and Bielecka, A.A. and Lesker, T.R. and Wyler, E. and Landthaler, M. and Mantei, A. and Meisel, C. and Caesar, S. and Thiebeault, C. and Corman, V. and Marko, L. and Suttorp, N. and Strowig, T. and Kurth, F. and Sander, L.E. and Li, Y. and Kirwan, J.A. and Forslund, S.K. and Opitz, B. |
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| Abstract: | The clinical course of the 2019 coronavirus disease (COVID-19) is variable and to a substantial degree still unpredictable, especially in persons who have neither been vaccinated nor recovered from previous infection. We hypothesized that disease progression and inflammatory responses were associated with alterations in the microbiome and metabolome. To test this, we integrated metagenome, metabolome, cytokine, and transcriptome profiles of longitudinally collected samples from hospitalized COVID-19 patients at the beginning of the pandemic (before vaccines or variants of concern) and non-infected controls, and leveraged detailed clinical information and post-hoc confounder analysis to identify robust within- and cross-omics associations. Severe COVID-19 was directly associated with a depletion of potentially beneficial intestinal microbes mainly belonging to Clostridiales, whereas oropharyngeal microbiota disturbance appeared to be mainly driven by antibiotic use. COVID-19 severity was also associated with enhanced plasma concentrations of kynurenine, and reduced levels of various other tryptophan metabolites, lysophosphatidylcholines, and secondary bile acids. Decreased abundance of Clostridiales potentially mediated the observed reduction in 5-hydroxytryptophan levels. Moreover, altered plasma levels of various tryptophan metabolites and lower abundances of Clostridiales explained significant increases in the production of IL-6, IFNγ and/or TNFα. Collectively, our study identifies correlated microbiome and metabolome alterations as a potential contributor to inflammatory dysregulation in severe COVID-19. |
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| Keywords: | COVID-19, Multi-omics, Metabolomics, Microbiota, Immune Response, Inflammation |
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| Source: | bioRxiv |
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| Publisher: | Cold Spring Harbor Laboratory Press |
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| Article Number: | 2022.12.02.518860 |
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| Date: | 2 December 2022 |
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| Official Publication: | https://doi.org/10.1101/2022.12.02.518860 |
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| Related to: | |
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