Integrated analysis of gut microbiome and host immune responses in COVID-19

Abstract

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.

Keywords

COVID-19 / SARS-COV-2 / gut microbiome / immune response

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Acknowledgements

This work was supported by grants from National Natural Science Foundation of China (Nos. 8210010124, 81890994, and 81861148030), Double First-Class Project (No. WF510162602) from the Ministry of Education, State Key Laboratory of Medical Genomics, Overseas Expertise Introduction Project for Discipline Innovation (111 Project, No. B17029), National Key R&D Program of China (No. 2019YFA0905902), Natural Science Foundation of Shanghai (Nos. 21ZR1480900 and 21YF1427900), Shanghai Clinical Research Center for Hematologic Disease (No. 19MC1910700), Shanghai Major Project for Clinical Medicine (No. 2017ZZ01002), Shanghai Shenkang Hospital Development Center (No. SHDC2020CR5002), Innovative Research Team of High-level Local Universities in Shanghai, Shanghai Collaborative Innovation Program on Regenerative Medicine and Stem Cell Research (No. 2019CXJQ01), Shanghai Jiao Tong University (No. YG2021QN19), Shanghai Guangci Translational Medical Research Development Foundation. We thank the support from Prof. Hai Fang, the ASTRA computing platform, and the high-throughput sequencing platform in the National Research Center for Translational Medicine (Shanghai). In addition, we thank the Pi computing platform in the Center for High-Performance Computing at Shanghai Jiao Tong University.

Compliance with ethics guidelines

Xiaoguang Xu, Wei Zhang, Mingquan Guo, Chenlu Xiao, Ziyu Fu, Shuting Yu, Lu Jiang, Shengyue Wang, Yun Ling, Feng Liu, Yun Tan, and Saijuan Chen declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000(5). Informed consent was obtained from all patients for being included in the study.

Electronic Supplementary Material

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