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Research
Hong Shan
Sun Yat-Sen University
Corresponding Author
ORCiD: https://orcid.org/0000-0003-1676-3320
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Gut ecosystem has profound effects on host physiology and health. Gastrointestinal (GI) symptoms were frequently observed in patients with COVID-19. Compared with other organs, gut antiviral response can result in more complicated immune responses because of the interactions between the gut microbiota and host immunity. However, there are still large knowledge gaps in the impact of COVID-19 on gut molecular profiles and commensal microbiome, hindering our comprehensive understanding of the pathogenesis of SARS-CoV-2 and the treatment of COVID-19.
Results: We performed longitudinal stool multi-omics profiling to systemically investigate the molecular phenomics alterations of gut ecosystem in COVID-19. Gut proteomes of COVID-19 were characterized by disturbed immune, proteolysis and redox homeostasis. The expression and glycosylation of proteins involved in neutrophil degranulation and migration were suppressed, while those of proteases were upregulated. The variable domains of Ig heavy chains were downregulated and the overall glycosylation of IgA heavy chain constant regions, IgGFc-binding protein, and J chain were suppressed with glycan-specific variations. There was a reduction of beneficial gut bacteria and an enrichment of bacteria derived deleterious metabolites potentially associated with multiple types of diseases (such as ethyl glucuronide). The reduction of Ig heave chain variable domains may contribute to the increase of some Bacteroidetes species. Many bacteria ceramide lipids with a C17-sphingoid based were downregulated in COVID-19. In many cases, the gut phenome did not restore two months after symptom onset.
Conclusions: Our study indicates widely disturbed gut molecular profiles which may play a role in the development of symptoms in COVID-19. Our findings also emphasis the need for ongoing investigation of the long-term gut molecular and microbial alterations during COVID-19 recovery process. Considering the gut ecosystem as a potential target could offer a valuable approach in managing the disease.
Keywords
Metaproteomics, Metabolomics, Glycoproteomics, Gut microbiome, COVID-19
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Supplementary file legends Figure S1. Deleterious metabolite identification by comparison between experimental and the reference MS/MS spectra, related to Figure 5. A-D. The experimental (upper penal) and reference (lower penal) MS/MS spectra show high similarities. Structures of key fragments are annotated. Table S1. Individual pathological and clinical details of the COVID-19 patients and controls, Related to Figure 1. Table S2. Expression matrices of global metaproteome, Related to Figure 2. 2.1. All identified protein groups. 2.2. All identified peptides. 2.3. Altered human protein groups. 2.4. Altered microbial protein groups. Table S3. Expression matrices of HILIC enriched metaproteome, Related to Figure 3. 3.1. All identified protein groups. 3.2. All identified peptides. 3.3. Altered human protein groups. 3.4. Altered Microbial protein groups. Table S4. N-glycoproteomics and O-glycoproteomics, Related to Figure 3. 4.1. PSM of all identified human N-glycopeptides using pGlyco. 4.2. Frequency of site-specific protein N-glycosylation. 4.3. Frequency of site-specific and glycan-specific protein N-glycosylation. 4.4. LFQ abundance of all identified glycopeptides using PEAKS. 4.5. Altered human O-glycopeptides in COVID-19 using PEAKS. Table S5. Relative abundance of taxonomic and functional groups of gut microbiome, Related to Figure 4. S5.1. Relative abundance of taxonomic groups of gut microbiome. S5.2. Relative abundance of functional groups of gut microbiome. S5.3. Associations between altered host proteins and gut microbiome. Table S6. Altered metabolome, Related to Figure 5. S6.1. Metabolites differentiating COVID-19 patients from healthy controls. S6.2. Correlations between altered gut microbiome and metabolites. Table S7. Expression matrices and differential analysis of lipidomics dataset, Related to Figure 6.
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This is a preprint. It has not completed peer review.
Research
Hong Shan
Sun Yat-Sen University
Corresponding Author
ORCiD: https://orcid.org/0000-0003-1676-3320
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 22 Feb, 2021
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
General Microbiology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Gut ecosystem has profound effects on host physiology and health. Gastrointestinal (GI) symptoms were frequently observed in patients with COVID-19. Compared with other organs, gut antiviral response can result in more complicated immune responses because of the interactions between the gut microbiota and host immunity. However, there are still large knowledge gaps in the impact of COVID-19 on gut molecular profiles and commensal microbiome, hindering our comprehensive understanding of the pathogenesis of SARS-CoV-2 and the treatment of COVID-19.
Results: We performed longitudinal stool multi-omics profiling to systemically investigate the molecular phenomics alterations of gut ecosystem in COVID-19. Gut proteomes of COVID-19 were characterized by disturbed immune, proteolysis and redox homeostasis. The expression and glycosylation of proteins involved in neutrophil degranulation and migration were suppressed, while those of proteases were upregulated. The variable domains of Ig heavy chains were downregulated and the overall glycosylation of IgA heavy chain constant regions, IgGFc-binding protein, and J chain were suppressed with glycan-specific variations. There was a reduction of beneficial gut bacteria and an enrichment of bacteria derived deleterious metabolites potentially associated with multiple types of diseases (such as ethyl glucuronide). The reduction of Ig heave chain variable domains may contribute to the increase of some Bacteroidetes species. Many bacteria ceramide lipids with a C17-sphingoid based were downregulated in COVID-19. In many cases, the gut phenome did not restore two months after symptom onset.
Conclusions: Our study indicates widely disturbed gut molecular profiles which may play a role in the development of symptoms in COVID-19. Our findings also emphasis the need for ongoing investigation of the long-term gut molecular and microbial alterations during COVID-19 recovery process. Considering the gut ecosystem as a potential target could offer a valuable approach in managing the disease.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
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