Guild-Level Microbiome Signature Associated with COVID-19 Severity and Prognosis
ABSTRACT Coronavirus disease 2019 (COVID-19) severity has been associated with alterations of the gut microbiota. However, the relationship between gut microbiome alterations and COVID-19 prognosis remains elusive. Here, we performed a genome-resolved metagenomic analysis on fecal samples from 300 i...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-02-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mbio.03519-22 |
| _version_ | 1811163332566056960 |
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| author | Mingquan Guo Guojun Wu Yun Tan Yan Li Xin Jin Weiqiang Qi Xiaokui Guo Chenhong Zhang Zhaoqin Zhu Liping Zhao |
| author_facet | Mingquan Guo Guojun Wu Yun Tan Yan Li Xin Jin Weiqiang Qi Xiaokui Guo Chenhong Zhang Zhaoqin Zhu Liping Zhao |
| author_sort | Mingquan Guo |
| collection | DOAJ |
| description | ABSTRACT Coronavirus disease 2019 (COVID-19) severity has been associated with alterations of the gut microbiota. However, the relationship between gut microbiome alterations and COVID-19 prognosis remains elusive. Here, we performed a genome-resolved metagenomic analysis on fecal samples from 300 in-hospital COVID-19 patients, collected at the time of admission. Among the 2,568 high quality metagenome-assembled genomes (HQMAGs), redundancy analysis identified 33 HQMAGs which showed differential distribution among mild, moderate, and severe/critical severity groups. Co-abundance network analysis determined that the 33 HQMAGs were organized as two competing guilds. Guild 1 harbored more genes for short-chain fatty acid biosynthesis, and fewer genes for virulence and antibiotic resistance, compared with Guild 2. Based on average abundance difference between the two guilds, the guild-level microbiome index (GMI) classified patients from different severity groups (average AUROC [area under the receiver operating curve] = 0.83). Moreover, age-adjusted partial Spearman’s correlation showed that GMIs at admission were correlated with 8 clinical parameters, which are predictors for COVID-19 prognosis, on day 7 in hospital. In addition, GMI at admission was associated with death/discharge outcome of the critical patients. We further validated that GMI was able to consistently classify patients with different COVID-19 symptom severities in different countries and differentiated COVID-19 patients from healthy subjects and pneumonia controls in four independent data sets. Thus, this genome-based guild-level signature may facilitate early identification of hospitalized COVID-19 patients with high risk of more severe outcomes at time of admission. IMPORTANCE Previous reports on the associations between COVID-19 and gut microbiome have been constrained by taxonomic-level analysis and overlook the interaction between microbes. By applying a genome-resolved, reference-free, guild-based metagenomic analysis, we demonstrated that the relationship between gut microbiota and COVID-19 is genome-specific instead of taxon-specific or even species-specific. Moreover, the COVID-19-associated genomes were not independent but formed two competing guilds, with Guild 1 potentially beneficial and Guild 2 potentially more detrimental to the host based on comparative genomic analysis. The dominance of Guild 2 over Guild 1 at time of admission was associated with hospitalized COVID-19 patients at high risk for more severe outcomes. Moreover, the guild-level microbiome signature is not only correlated with the symptom severity of COVID-19 patients, but also differentiates COVID-19 patients from pneumonia controls and healthy subjects across different studies. Here, we showed the possibility of using genome-resolved and guild-level microbiome signatures to identify hospitalized COVID-19 patients with a high risk of more severe outcomes at the time of admission. |
| first_indexed | 2024-04-10T06:43:34Z |
| format | Article |
| id | doaj.art-0cc2db11212a49afbcd3fa22d8a48865 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-04-10T06:43:34Z |
| publishDate | 2023-02-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-0cc2db11212a49afbcd3fa22d8a488652023-02-28T14:06:25ZengAmerican Society for MicrobiologymBio2150-75112023-02-0114110.1128/mbio.03519-22Guild-Level Microbiome Signature Associated with COVID-19 Severity and PrognosisMingquan Guo0Guojun Wu1Yun Tan2Yan Li3Xin Jin4Weiqiang Qi5Xiaokui Guo6Chenhong Zhang7Zhaoqin Zhu8Liping Zhao9Department of Laboratory Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaDepartment of Biochemistry and Microbiology, School of Environmental and Biological Sciences and Center for Microbiome, Nutrition, and Health, New Jersey Institute for Food, Nutrition, and Health, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USAShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai, ChinaState Key Laboratory of Microbial Metabolism and Ministry of Education Key Laboratory of Systems Biomedicine, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Laboratory Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaDepartment of Laboratory Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaSchool of Global Health, Chinese Center for Tropical Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaState Key Laboratory of Microbial Metabolism and Ministry of Education Key Laboratory of Systems Biomedicine, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Laboratory Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaState Key Laboratory of Microbial Metabolism and Ministry of Education Key Laboratory of Systems Biomedicine, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, ChinaABSTRACT Coronavirus disease 2019 (COVID-19) severity has been associated with alterations of the gut microbiota. However, the relationship between gut microbiome alterations and COVID-19 prognosis remains elusive. Here, we performed a genome-resolved metagenomic analysis on fecal samples from 300 in-hospital COVID-19 patients, collected at the time of admission. Among the 2,568 high quality metagenome-assembled genomes (HQMAGs), redundancy analysis identified 33 HQMAGs which showed differential distribution among mild, moderate, and severe/critical severity groups. Co-abundance network analysis determined that the 33 HQMAGs were organized as two competing guilds. Guild 1 harbored more genes for short-chain fatty acid biosynthesis, and fewer genes for virulence and antibiotic resistance, compared with Guild 2. Based on average abundance difference between the two guilds, the guild-level microbiome index (GMI) classified patients from different severity groups (average AUROC [area under the receiver operating curve] = 0.83). Moreover, age-adjusted partial Spearman’s correlation showed that GMIs at admission were correlated with 8 clinical parameters, which are predictors for COVID-19 prognosis, on day 7 in hospital. In addition, GMI at admission was associated with death/discharge outcome of the critical patients. We further validated that GMI was able to consistently classify patients with different COVID-19 symptom severities in different countries and differentiated COVID-19 patients from healthy subjects and pneumonia controls in four independent data sets. Thus, this genome-based guild-level signature may facilitate early identification of hospitalized COVID-19 patients with high risk of more severe outcomes at time of admission. IMPORTANCE Previous reports on the associations between COVID-19 and gut microbiome have been constrained by taxonomic-level analysis and overlook the interaction between microbes. By applying a genome-resolved, reference-free, guild-based metagenomic analysis, we demonstrated that the relationship between gut microbiota and COVID-19 is genome-specific instead of taxon-specific or even species-specific. Moreover, the COVID-19-associated genomes were not independent but formed two competing guilds, with Guild 1 potentially beneficial and Guild 2 potentially more detrimental to the host based on comparative genomic analysis. The dominance of Guild 2 over Guild 1 at time of admission was associated with hospitalized COVID-19 patients at high risk for more severe outcomes. Moreover, the guild-level microbiome signature is not only correlated with the symptom severity of COVID-19 patients, but also differentiates COVID-19 patients from pneumonia controls and healthy subjects across different studies. Here, we showed the possibility of using genome-resolved and guild-level microbiome signatures to identify hospitalized COVID-19 patients with a high risk of more severe outcomes at the time of admission.https://journals.asm.org/doi/10.1128/mbio.03519-22COVID-19guildgut microbiome |
| spellingShingle | Mingquan Guo Guojun Wu Yun Tan Yan Li Xin Jin Weiqiang Qi Xiaokui Guo Chenhong Zhang Zhaoqin Zhu Liping Zhao Guild-Level Microbiome Signature Associated with COVID-19 Severity and Prognosis mBio COVID-19 guild gut microbiome |
| title | Guild-Level Microbiome Signature Associated with COVID-19 Severity and Prognosis |
| title_full | Guild-Level Microbiome Signature Associated with COVID-19 Severity and Prognosis |
| title_fullStr | Guild-Level Microbiome Signature Associated with COVID-19 Severity and Prognosis |
| title_full_unstemmed | Guild-Level Microbiome Signature Associated with COVID-19 Severity and Prognosis |
| title_short | Guild-Level Microbiome Signature Associated with COVID-19 Severity and Prognosis |
| title_sort | guild level microbiome signature associated with covid 19 severity and prognosis |
| topic | COVID-19 guild gut microbiome |
| url | https://journals.asm.org/doi/10.1128/mbio.03519-22 |
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