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Specific roles of gut microbes in COVID‐19 progression are critical. However, the circumstantial mechanism remains elusive. In this study, shotgun metagenomic or metatranscriptomic sequencing was performed on fecal samples collected from 13 COVID‐19 patients and controls. We analyzed the structure of gut microbiota, identified the characteristic bacteria, and selected biomarkers. Further, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations were employed to correlate the taxon alterations and corresponding functions. The gut microbiota of COVID‐19 patients was characterized by the enrichment of opportunistic pathogens and depletion of commensals. The abundance of Bacteroides spp. displayed an inverse relationship with COVID‐19 severity, whereas Actinomyces oris , Escherichia coli , and Streptococcus parasanguini were positively correlated with disease severity. The genes encoding oxidoreductase were significantly enriched in gut microbiome of COVID‐19 group. KEGG annotation indicated that the expression of ABC transporter was upregulated, while the synthesis pathway of butyrate was aberrantly reduced. Furthermore, increased metabolism of lipopolysaccharide, polyketide sugar, sphingolipids, and neutral amino acids were found. These results suggested the gut microbiome of COVID‐19 patients was in a state of oxidative stress. Healthy gut microbiota may enhance antiviral defenses via butyrate metabolism, whereas the accumulation of opportunistic and inflammatory bacteria may exacerbate COVID‐19 progression.

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