Emerging evidence indicates that the gut microbiome contributes to the host immune response to infectious diseases.Here,to explore the role of the gut microbiome in the host immune responses in COVID-19,we conducted shotgun metagenomic sequencing and immune profiling of 14 severe/critical and 24 mild/moderate COVID-19 cases as well as 31 healthy control samples.We found that the diversity of the gut microbiome was reduced in severe/critical COVID-19 cases compared to mild/moderate ones.We identified the abundance of some gut microbes altered post-SARS-CoV-2 infection and related to disease severity,such as Enterococcus faecium,Coprococcus comes,Roseburia intestinalis,Akkermansia muciniphila,Bacteroides cellulosilyticus and Blautia obeum.We further analyzed the correlation between the abundance of gut microbes and host responses,and obtained a correlation map between clinical features of COVID-19 and 16 severity-related gut microbe,including Coprococcus comes that was positively correlated with CD3+/CD4+/CD8+lymphocyte counts.In addition,an integrative analysis of gut microbiome and the transcriptome of peripheral blood mononuclear cells(PBMCs)showed that genes related to viral transcription and apoptosis were up-regulated in Coprococcus comes low samples.Moreover,a number of metabolic pathways in gut microbes were also found to be differentially enriched in severe/critical or mild/moderate COVID-19 cases,including the superpathways of polyamine biosynthesis Ⅱ and sulfur oxidation that were suppressed in severe/critical COVID-19.Together,our study highlighted a potential regulatory role of severity related gut microbes in the immune response of host.

Shanghai Institute of Hematology,State Key Laboratory of Medical Genomics,National Research Center for Translational Medicine at Shanghai,Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China;School of Life Sciences and Biotechnology,Shanghai Jiao Tong University,Shanghai 200240,China;Shanghai Public Health Clinical Center,Shanghai 201508,China;Department of Laboratory Medicine,Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China

[1]Xiaoguang Xu;Wei Zhang;Mingquan Guo;Chenlu Xiao;Ziyu Fu;Shuting Yu;Lu Jiang;Shengyue Wang;Yun Ling;Feng Liu;Yun Tan;Saijuan Chen-.Integrated analysis of gut microbiome and host immune responses in COVID-19)[J].医学前沿,2022(02):263-275

cellulosilyticus,obeum,CD8+lymphocyte,superpathways

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