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COVID-19 is mainly associated with respiratory distress syndrome, but a subset of patients often present gastrointestinal (GI) symptoms. Imbalances of gut microbiota have been previously linked to respiratory virus infection. Understanding how the gut–lung axis affects the progression of COVID-19 can provide a novel framework for therapies and management. In this study, we examined the gut microbiota of patients with COVID-19 ( n  = 47) and compared it to healthy controls ( n  = 19). Using shotgun metagenomic sequencing, we have identified four microorganisms unique in COVID-19 patients, namely  Streptococcus thermophilus ,  Bacteroides oleiciplenus ,  Fusobacterium ulcerans , and  Prevotella bivia . The abundances of  Bacteroides stercoris ,  B. vulgatus ,  B. massiliensis ,  Bifidobacterium longum ,  Streptococcus thermophilus ,  Lachnospiraceae bacterium  5163FAA,  Prevotella bivia ,  Erysipelotrichaceae bacterium  6145, and  Erysipelotrichaceae bacterium  2244A were enriched in COVID-19 patients, whereas the abundances of  Clostridium nexile ,  Streptococcus salivarius ,  Coprococcus catus ,  Eubacterium hallii ,  Enterobacter aerogenes , and  Adlercreutzia equolifaciens  were decreased ( p  < 0.05). The relative abundance of butyrate-producing  Roseburia inulinivorans  is evidently depleted in COVID-19 patients, while the relative abundances of  Paraprevotella  sp. and the probiotic  Streptococcus thermophilus  were increased. We further identified 30 KEGG orthology (KO) modules overrepresented, with 7 increasing and 23 decreasing modules. Notably, 15 optimal microbial markers were identified using the random forest model to have strong diagnostic potential in distinguishing COVID-19. Based on Spearman’s correlation, eight species were associated with eight clinical indices. Moreover, the increased abundance of  Bacteroidetes  and decreased abundance of  Firmicutes  were also found across clinical types of COVID-19. Our findings suggest that the alterations of gut microbiota in patients with COVID-19 may influence disease severity. Our COVID-19 classifier, which was cross-regionally verified, provides a proof of concept that a set of microbial species markers can distinguish the presence of COVID-19.

Microbiome Profiling Using Shotgun Metagenomic Sequencing Identified Unique Microorganisms in COVID-19 Patients With Altered Gut Microbiota