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. 2025 Jul 7:12:1593007.
doi: 10.3389/fmed.2025.1593007. eCollection 2025.

Biological characteristics of SARS-CoV-2 resistant populations by integrated gut microbiota sequencing, metabolomics, and proteomics: a cohort comparison study

Huachong Xu #  1 , Haoxuan Li #  2 , Junhao Xu  3 , Yaoxin Chen  4 , Li Deng  1 , Xiaoyin Chen  1 , Yinji Xu  3   5
Affiliations

Biological characteristics of SARS-CoV-2 resistant populations by integrated gut microbiota sequencing, metabolomics, and proteomics: a cohort comparison study

Huachong Xu et al. Front Med (Lausanne). .

Abstract

Objective: Most research reports on COVID-19 infections have focused on the correlation between the severity of the disease symptoms and immune deficits, while the mechanisms affecting the susceptibility to SARS-CoV-2 remain largely unknown. The study aimed to comprehensively analyze the differences in immunity, gut microbiota, metabolism, and proteomics between the SARS-CoV-2 resistant population and the susceptible population.

Methods and results: In this cohort comparison study, participants were rigorously selected based on inclusion and exclusion criteria in a continuous enrollment manner using combined questionnaires and clinical data, ultimately including 25 SARS-CoV-2 resistant volunteers versus 16 SARS-CoV-2 infected patients. The clinical information of the participants was recorded in detail, and fecal and blood samples were collected in a standardized manner for subsequent multi-omics analysis, including gut microbiota sequencing, metabolomics, and proteomics. This study has preliminarily elucidated the characteristics of the gut microbiota, serum metabolites, and serum proteins in the SARS-CoV-2 resistant population. It exhibits a unique metabolic signature characterized by elevated levels of serum phosphatidylinositol and the abundance of Prevotella, which may serve as a potential predictive biomarker for resistance to SARS-CoV-2.

Conclusion: Given the crucial role of phosphatidylinositol in cell membrane architecture and viral infectivity, this study provides a promising entry point for further research into the pathogenesis and prevention strategies of COVID-19.

Keywords: COVID-19; SARS-CoV-2; gut microbiota; metabolomics; multiomics; phosphatidylinositols; proteomics; resistant population.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Participant flow diagram.
FIGURE 2
FIGURE 2
Clinical immune indexes and complete blood count analysis. “*” indicates P < 0.05 for comparison between two groups. “**” indicates P < 0.01 for comparison between two groups. “***” indicates P < 0.001 for comparison between two groups.
FIGURE 3
FIGURE 3
Differences in gut microbiota between the SARS-CoV-2 resistance group and the infection group. (A) Violin diagram of alpha diversity; (B) partial least squares discriminant analysis of gut microbiota; (C) the result chart of differential bacterial genera screening at the genus level between the COVID-19 infection group and the COVID-19 resistant group; (D) linear discriminant analysis effect size analysis; microbial features were classified based on both statistical significance and biological effect size.
FIGURE 4
FIGURE 4
Between-group comparative analysis of serum metabolites. (A) Partial least squares discriminant analysis of metabolites; (B) volcano plot for differential metabolites; (C) metabolomics cluster analysis plot; (D) Kyoto Encyclopedia of Genes and Genomes enrichment pathway of metabolites.
FIGURE 5
FIGURE 5
Correlation between the gut microbiota and metabolites. (A) Heatmap of joint analysis of metabolomics and gut microbiota; (B) diagram of differential metabolites and differential microbiota network regulation. “*” indicates P < 0.05 for comparison between two groups. “**” indicates P < 0.01 for comparison between two groups.
FIGURE 6
FIGURE 6
Proteomics and its correlation between metabolites. (A) Principal component analysis of proteomics; (B) proteomics cluster analysis plot; (C) volcano plot of differential protein; (D) differential protein enrichment pathway plot; (E) heatmap of joint analysis of differential metabolites and differential proteins. “*” indicates P < 0.05 for comparison between two groups. “**” indicates P < 0.01 for comparison between two groups. Protein identifiers and their functional descriptions are provided in Supplementary Table 1.
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References

    1. Ye Q, Zhang T, Lu D. Potential false-positive reasons for SARS-CoV-2 antibody testing and its solution. J Med Virol. (2021) 93:4242–6. 10.1002/jmv.26937 - DOI - PMC - PubMed
    1. Almasi-Hashiani A, Doosti-Irani A, Mansournia M. Case fatality rate of COVID-19: Meta-analysis approach. Arch Iran Med. (2020) 23:644–6. 10.34172/aim.2020.78 - DOI - PubMed
    1. Rajgor D, Lee M, Archuleta S, Bagdasarian N, Quek S. The many estimates of the COVID-19 case fatality rate. Lancet Infect Dis. (2020) 20:776–7. 10.1016/S1473-3099(20)30244-9 - DOI - PMC - PubMed
    1. Ibn-Mohammed T, Mustapha K, Godsell J, Adamu Z, Babatunde K, Akintade D, et al. A critical analysis of the impacts of COVID-19 on the global economy and ecosystems and opportunities for circular economy strategies. Resour Conserv Recycl. (2021) 164:105169. 10.1016/j.resconrec.2020.105169 - DOI - PMC - PubMed
    1. Ye Q, Lai E, Luft F, Persson P, Mao J. SARS- CoV-2 effects on the renin-angiotensin-aldosterone system, therapeutic implications. Acta Physiol (Oxf). (2021) 231:e13608. 10.1111/apha.13608 - DOI - PMC - PubMed

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