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Published November 3, 2022 | Version v1
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Immunomodulatory fecal metabolites are associated with mortality in COVID-19 patients with respiratory failure

Creators

  • 1. University of Chicago

Description

Respiratory failure and mortality from COVID-19 result from virus- and inflammation-induced lung tissue damage. The intestinal microbiome and associated metabolites are implicated in immune responses to respiratory viral infections, however their impact on progression of severe COVID-19 remains unclear. We prospectively enrolled 71 patients with COVID-19 associated critical illness, collected fecal specimens within 3 days of medical intensive care unit admission, defined microbiome compositions by shotgun metagenomic sequencing, and quantified microbiota-derived metabolites (NCT #04552834). Of the 71 patients, 39 survived and 32 died. Mortality was associated with increased representation of Proteobacteria in the fecal microbiota and decreased concentrations of fecal secondary bile acids and desaminotyrosine (DAT). A microbiome metabolic profile (MMP) that accounts for fecal secondary bile acids and desaminotyrosine concentrations was independently associated with progression of respiratory failure leading to mechanical ventilation. Our findings demonstrate that fecal microbiota composition and microbiota-derived metabolite concentrations can predict the trajectory of respiratory function and death in patients with severe SARS-Cov-2 infection and suggest that the gut-lung axis plays an important role in the recovery from COVID-19.

Data availability

All data are available to the public. Raw sequencing data generated in this study have been deposited onto the National Center for Biotechnology Information (NCBI) Sequence Read Archive (SRA) under accession number PRJNA842425. Raw metabolomic data generated in this study have been deposited onto Metabolights under accession number MTBLS5288. All processed data in this study are hosted on both GitHub (https://github.com/DFI-Bioinformatics/SARS-CoV-2) as well as Zenodo (https://doi.org/10.5281/zenodo.6858446).

All code used in this study for analyses and to generate figures is available both at GitHub (https://github.com/DFI-Bioinformatics/SARS-CoV-2) and Zenodo ( https://doi.org/10.5281/zenodo.6858446https://doi.org/10.5281/zenodo.6858446).

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Immunomodulatory-fecal-metabolites-are-associated-with-mortality-in-COVID-19-patients-with-respiratory-failure.pdf

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Additional details

Identifiers

DOI
10.1038/s41467-022-34260-2
Other
oai:uchicago.tind.io:5447

Funding

National Institutes of Health
T32 HL-007605
National Institutes of Health
P01 CA023766
National Institutes of Health
NHLBI K23 HL148387

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Medicine, Public Health Sciences
Center(s) or Institute(s)
Duchossois Family Institute