Gastroenterology

Gastroenterology

Volume 162, Issue 2, February 2022, Pages 548-561.e4
Gastroenterology

Original Research
Full Report: Basic and Translational—Alimentary Tract
Prolonged Impairment of Short-Chain Fatty Acid and L-Isoleucine Biosynthesis in Gut Microbiome in Patients With COVID-19

https://doi.org/10.1053/j.gastro.2021.10.013Get rights and content

Background and Aims

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with altered gut microbiota composition. Phylogenetic groups of gut bacteria involved in the metabolism of short chain fatty acids (SCFAs) were depleted in SARS-CoV-2–infected patients. We aimed to characterize a functional profile of the gut microbiome in patients with COVID-19 before and after disease resolution.

Methods

We performed shotgun metagenomic sequencing on fecal samples from 66 antibiotics-naïve patients with COVID-19 and 70 non–COVID-19 controls. Serial fecal samples were collected (at up to 6 times points) during hospitalization and beyond 1 month after discharge. We assessed gut microbial pathways in association with disease severity and blood inflammatory markers. We also determined changes of microbial functions in fecal samples before and after disease resolution and validated these functions using targeted analysis of fecal metabolites.

Results

Compared with non–COVID-19 controls, patients with COVID-19 with severe/critical illness showed significant alterations in gut microbiome functionality (P < .001), characterized by impaired capacity of gut microbiome for SCFA and L-isoleucine biosynthesis and enhanced capacity for urea production. Impaired SCFA and L-isoleucine biosynthesis in gut microbiome persisted beyond 30 days after recovery in patients with COVID-19. Targeted analysis of fecal metabolites showed significantly lower fecal concentrations of SCFAs and L-isoleucine in patients with COVID-19 before and after disease resolution. Lack of SCFA and L-isoleucine biosynthesis significantly correlated with disease severity and increased plasma concentrations of CXCL-10, NT- proB-type natriuretic peptide, and C-reactive protein (all P < .05).

Conclusions

Gut microbiome of patients with COVID-19 displayed impaired capacity for SCFA and L-isoleucine biosynthesis that persisted even after disease resolution. These 2 microbial functions correlated with host immune response underscoring the importance of gut microbial functions in SARS-CoV-2 infection pathogenesis and outcome.

Keywords

Coronavirus
Gut Microbiome
Microbial Functions
SCFAs

Abbreviations used in this paper

COVID-19
coronavirus disease 2019
CRP
C-reactive protein
FDR
false discovery rate
IQR
interquartile range
LDH
lactate dehydrogenase
MaAsLin
multivariate analysis by linear models
NT-proBNP
N-terminal B-type natriuretic peptide
PLT
levels of platelet count
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SCFA
short chain fatty acid

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Conflicts of interest The authors disclose no conflicts.

Funding This study was supported by a donation from Koon Wah Mirror Group and was additionally supported in part by InnoHK, The Government of Hong Kong, Special Administrative Region of the People’s Republic of China.

Data availability Raw sequence data generated for this study are available in the Sequence Read (archive under BioProject accession PRJNA689961;. https://www.ncbi.nlm.nih.gov/bioproject/ PRJNA689961).

Authors share co-first authorship.

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