AUTHOR=Li Sijia , Yang Siyuan , Zhou Yuzheng , Disoma Cyrollah , Dong Zijun , Du Ashuai , Zhang Yongxing , Chen Yong , Huang Weiliang , Chen Junru , Song Deqiang , Chen Zongpeng , Liu Pinjia , Li Shiqin , Zheng Rong , Liu Sixu , Razzaq Aroona , Chen Xuan , Tao Siyi , Yu Chengping , Feng Tianxu , Liao Wenyan , Peng Yousong , Jiang Taijiao , Huang Jufang , Wu Wei , Hu Liqiang , Wang Linghang , Li Shanni , Xia Zanxian 

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

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.712081

DOI=10.3389/fmicb.2021.712081

ISSN=1664-302X

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