Gut microbiota dysbiosis is associated with altered tryptophan metabolism and dysregulated inflammatory response in COVID-19

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 metagenomic, metabolomic, cytokine, and transcriptomic 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.

Morgan Essex, Belén Millet Pascual-Leone, Ulrike Löber, Matthias Kuhring, Bowen Zhang, Ulrike Brüning, Raphaela Fritsche-Guenther, Marta Krzanowski, Facundo Fiocca Verneño, Sophia Brumhard, Ivo Röwekamp, Agata Anna Bielecka, Till Robin Lesker, Emanuel Wyler, Markus Landthaler, Andrej Mantei, Christian Meisel, Sandra Caesar, Charlotte Thibault, Victor M. Corman, Lajos Marko, Norbert Suttorp, Till Strowig, Florian Kurth, Leif E. Sander, Yang Li, Jennifer A. Kirwan, Sofia K. Forslund, Bastian Opitz