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

Abstract

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 (<i>n</i> = 47) and compared it to healthy controls (<i>n</i> = 19). Using shotgun metagenomic sequencing, we have identified four microorganisms unique in COVID-19 patients, namely <i>Streptococcus thermophilus</i>, <i>Bacteroides oleiciplenus</i>, <i>Fusobacterium ulcerans</i>, and <i>Prevotella bivia</i>. The abundances of <i>Bacteroides stercoris</i>, <i>B. vulgatus</i>, <i>B. massiliensis</i>, <i>Bifidobacterium longum</i>, <i>Streptococcus thermophilus</i>, <i>Lachnospiraceae bacterium</i> 5163FAA, <i>Prevotella bivia</i>, <i>Erysipelotrichaceae bacterium</i> 6145, and <i>Erysipelotrichaceae bacterium</i> 2244A were enriched in COVID-19 patients, whereas the abundances of <i>Clostridium nexile</i>, <i>Streptococcus salivarius</i>, <i>Coprococcus catus</i>, <i>Eubacterium hallii</i>, <i>Enterobacter aerogenes</i>, and <i>Adlercreutzia equolifaciens</i> were decreased (<i>p</i> < 0.05). The relative abundance of butyrate-producing <i>Roseburia inulinivorans</i> is evidently depleted in COVID-19 patients, while the relative abundances of <i>Paraprevotella</i> sp. and the probiotic <i>Streptococcus thermophilus</i> 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 <i>Bacteroidetes</i> and decreased abundance of <i>Firmicutes</i> 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.