Gut Microbiome Disruption Following SARS-CoV-2: A Review
Abstract
:1. Introduction
2. Methods
2.1. Systematic Review
2.2. Longitudinal Study Methodology
Bioinformatics and Statistical Analysis
3. Changes in Gut Microbiome during and Following Acute COVID-19
3.1. Acute COVID-19
3.2. COVID-19 Severity and Gut Microbiome Changes
3.3. Gut Microbiome in Patients Recovering from COVID-19
4. Longitudinal Study of Microbiome Changes: A Case Series
5. Microbiome Changes and PCS
6. Microbiome Manipulation and Treatment Potential
7. Discussion and Conclusions
Supplementary Materials
Funding
Acknowledgments
Conflicts of Interest
References
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Author, Country | COVID-19 Patients, Type of Study | Timing | Microbiome Changes | Measurement Method |
---|---|---|---|---|
Righi, Italy [4] | 82 patients | Samples collected <2 weeks of hospitalization | 16S rRNA gene sequencing. Increased opportunistic pathogens higher in severe COVID-19. Enterococcus: highest number of correlations with therapy (including antibiotics). Dorea, Agathobacter, Roseburia, and Barnesiella negatively correlated with antibiotic therapy | Alpha (Shannon’s index) and beta diversity metrics (Jaccard distance, weighted UniFrac distance) |
Gaibani, Italy [20] | 57 (32% ICU) and 100 controls | Cross sectional, case—control. Samples collected <week 1 of hospitalization | 16S rRNA gene sequencing. Dysbiosis and over-representation of Enterococcus, especially in ICU; loss of alpha diversity | Alpha diversity metrics, number of observed ASV, and inverse Simpson index |
Mazzarelli, Italy [21] | 15 hospitalized patients (6 in ICU), 8 controls | Cross sectional, case—control. Swabs collected at hospitalization | 16S rRNA gene sequencing. Patients in the ICU had lower microbial richness. Increase in Proteobacteria and decrease in Fusobacteria and Spirochetes in infected vs. controls | Alpha diversity and richness were assessed using Shannon indices and Chao1 |
Moreira-Rosário, Portugal [22] | Hospitalized and outpatients (WHO Clinical Progression Scale: 19 mild, 37 moderate, 59 severe) | Cross-sectional. Samples collected after enrolment | 16S rRNA gene sequencing. Moderate and severe disease vs. mild had dysbiosis with lower Firmicutes/Bacteroidetes ratio, higher abundance of Proteobacteria, and lower abundance of Roseburia and Lachnospira | Shannon diversity index |
Khan, India [23] | 10 asymptomatic, 10 mild symptoms (no oxygen), 10 severe; 10 controls | Cross sectional, case–control. Samples collected at admission | 16S rRNA gene sequencing. Decrease in diversity with increasing COVID-19 severity. Reduction in Prevotella, affecting the gut mucin glycoprotein maintenance, which interacts with the immune system | Alpha diversity and richness (InvSimpson and Fisher indices); Beta Diversity analyzed by LDA Effect Size |
Reinold, Germany [24] | 26 patients classified as severe, 12 as critical, 79 non-severe (WHO) | 117 patients and 95 controls. Cross sectional. Timing of collection unknown | 16S rRNA gene sequencing. Patients had lower richness with increased Proteobacteria and Bacteroidetes and decrease vs. control. | Shannon diversity index, observed features (ASVs), and Pielou’s evenness index |
Newsome, United States [25] | 94 patients (50 acute infection, 9 recovered, 34 controls ICU admitted) | Cross sectional, case–control. Samples collected <3 days of ICU admission | 16S rRNA gene sequencing. Patients clustered in the recovered and non-infected groups. Recovered similar to non-infected. Similar Shannon index across groups | Shannon diversity index |
Righi, Italy * (unpublished) | Healthcare workers (n = 6). Day 14 and >day 30 after negativization collection | 6 to 20 weeks | 16S rRNA gene sequencing. Bacteroides stable; Alistipes increase from day 14 after negativization. Faecalibacterium increased after negativization. Barnesiella increased. Roseburia decreased from day 14 after negativization | Alpha (Shannon’s index) and beta diversity metrics (Jaccard distance, weighted UniFrac distance) |
Kim, Korea [26] | Two paired samples from 12 patients; negative conversion for SARS-CoV-2 | 10 days median interval | 16S rRNA gene sequencing. Depletion of Bacteroidetes with tendency to rapidly reverse. Firmicutes/Bacteroidetes ratio higher in infected vs. recovered. Gut microbiota recovered after SARS-CoV-2 conversion | Faith’s phylogenetic diversity, Shannon’s index, and Pielou’s evenness |
Author, Country | Population, Type of Study | Timing | Microbiome Changes | Measurement Method |
---|---|---|---|---|
Liu, China [6] | 68 patients with >1 symptom 4 weeks after SARS-CoV-2 clearance | 6 months | 16S rRNA gene sequencing. Bacteria diversity and richness lower vs. controls. Significantly lower C. aerofaciens, F. prausnitzii, B. obeum and higher R. gnavus and B. vulgatus. | Shannon index diversity and Chao1 richness index |
Su, China [7] | 155 patients (79% > 1 symptom 4 weeks after recovery from COVID-19) | 14 months | Shotgun metagenomic sequencing Bacteria diversity (p = 0.004) and richness (p = 0.0003) lower than controls. Recovered patients had increased E. ramosum and R. gnavus and depletion of B. adolescentis and B. pseudocatenulatum. | Alpha diversity metrics (Shannon diversity, Chao1 richness) |
Chen, China [32] | 30 patients postconvalescence | 6 months | 16S rRNA gene sequencing. Richness lower in acute phase (median 217, IQR 164–266) vs. controls (median 432, IQR 332–468). Non-significant increase in Chao 1 index from acute to convalescence and postconvalescence phases. Low richness associated with reduced pulmonary function. | Chao 1 index |
Zhou, China [33] | 15 patients (12 with > 1 symptom) | 3 months | 16S rRNA gene sequencing. F. prausnitzii negatively correlated with chest tightness after activity and I. butyriciproducens with cough. Escherichia positively correlated with fatigue, chest tightness after activity, and myalgia. I. bartlettii positively correlated with anorexia and fatigue. | Spearman’s rank-based correlation test |
Vestad, Norway [34] | 83 patients (30% with respiratory impairment) | 3 months | 16S rRNA gene sequencing. Reduced alpha diversity. Increased abundance of 5 taxa and reduced of 20 taxa. Reduced Erysipelotrichaceae UCG-003 and increased Veillonella and Flavonifractor. | Alfa-diversity (Faith’s phylogenetic diversity and observed amplicon sequence variants). Beta diversity (Bray–Curtis) |
Liu, China [35] | 78 (Cluster, 42; Cluster 2, 36) > 1 symptoms at 4 weeks after infection | 6 months | WGS analysis. Cluster 1 (84% long COVID) different vs. Cluster 2 (44% long COVID). Bacteria diversity Cluster 1 lower than Cluster 2. Cluster 1 had increased opportunistic species (E. ramosum, C. bolteae, C. innocuum). | Shannon diversity index, MaAslin analysis |
Carneiro, US [36] | 34 patients, 15 with continuing or recurring symptoms > 4 weeks after infection | N/A | 16S rRNA gene sequencing. No significant differences between groups. Long COVID had lower ratio of ASV highly related to F. prausnitzii over genus Bacteroides (B. dorei, B. massiliensis, and B. thetaiotaomicron). | SELBAL analysis |
Zhang, China [37] | 55 patients with >1 symptom | 12 months | 16S rRNA gene sequencing. Decreased richness and diversity; Firmicutes less abundant, Actinobacteriota and Proteobacteria more abundant; decreased Clostridia and Coriobacteriia. SCFAs-producing symbionts significantly depleted. Veillonella enriched. | Sobs and Shannon index, PCoA of Bray–Curtis |
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Righi, E.; Dalla Vecchia, I.; Auerbach, N.; Morra, M.; Górska, A.; Sciammarella, C.; Lambertenghi, L.; Gentilotti, E.; Mirandola, M.; Tacconelli, E.; et al. Gut Microbiome Disruption Following SARS-CoV-2: A Review. Microorganisms 2024, 12, 131. https://doi.org/10.3390/microorganisms12010131
Righi E, Dalla Vecchia I, Auerbach N, Morra M, Górska A, Sciammarella C, Lambertenghi L, Gentilotti E, Mirandola M, Tacconelli E, et al. Gut Microbiome Disruption Following SARS-CoV-2: A Review. Microorganisms. 2024; 12(1):131. https://doi.org/10.3390/microorganisms12010131
Chicago/Turabian StyleRighi, Elda, Ilaria Dalla Vecchia, Nina Auerbach, Matteo Morra, Anna Górska, Concetta Sciammarella, Lorenza Lambertenghi, Elisa Gentilotti, Massimo Mirandola, Evelina Tacconelli, and et al. 2024. "Gut Microbiome Disruption Following SARS-CoV-2: A Review" Microorganisms 12, no. 1: 131. https://doi.org/10.3390/microorganisms12010131
APA StyleRighi, E., Dalla Vecchia, I., Auerbach, N., Morra, M., Górska, A., Sciammarella, C., Lambertenghi, L., Gentilotti, E., Mirandola, M., Tacconelli, E., & Sartor, A. (2024). Gut Microbiome Disruption Following SARS-CoV-2: A Review. Microorganisms, 12(1), 131. https://doi.org/10.3390/microorganisms12010131