Gut Microbiome Disruption Following SARS-CoV-2: A Review
Elda Righi, Ilaria Dalla Vecchia, Nina Auerbach, Matteo Morra, Anna Górska, Concetta Sciammarella, Lorenza Lambertenghi, Elisa Gentilotti, Massimo Mirandola, Evelina Tacconelli, Assunta Sartor
Microorganisms, doi:10.3390/microorganisms12010131
COVID-19 has been associated with having a negative impact on patients' gut microbiome during both active disease and in the post-acute phase. In acute COVID-19, rapid alteration of the gut microbiome composition was observed, showing on one side a reduction in beneficial symbionts (e.g., Roseburia, Lachnospiraceae) and on the other side an increase in opportunistic pathogens such as Enterococcus and Proteobacteria. Alpha diversity tends to decrease, especially initially with symptom onset and hospital admission. Although clinical recovery appears to align with improved gut homeostasis, this process could take several weeks, even in mild infections. Moreover, patients with COVID-19 post-acute syndrome showed changes in gut microbiome composition, with specific signatures associated with decreased respiratory function up to 12 months following acute disease. Potential treatments, especially probiotic-based therapy, are under investigation. Open questions remain on the possibility to use gut microbiome data to predict disease progression and on potential confounders that may impair result interpretation (e.g., concomitant therapies in the acute phase; reinfection, vaccines, and occurrence of novel conditions or diseases in the post-acute syndrome). Understanding the relationships between gut microbiome dynamics and disease progression may contribute to better understanding post-COVID syndrome pathogenesis or inform personalized treatment that can affect specific targets or microbiome markers.
Conflicts of Interest: The authors declare no conflicts of interest.
References
Alenazy, Aljohar, Alruwaili, Daghestani, Alonazi et al., Gut Microbiota Dynamics in Relation to Long-COVID-19 Syndrome: Role of Probiotics to Combat Psychiatric Complications, Metabolites,
doi:10.3390/metabo12100912Allie, Bradley, Mudunuru, Schultz, Graf et al., The establishment of resident memory B cells in the lung requires local antigen encounter, Nat. Immunol,
doi:10.1038/s41590-018-0260-6Baud, Dimopoulou Agri, Gibson, Reid, Giannoni, Using probiotics to flatten the curve of coronavirus disease COVID-2019 pandemic, Front. Public Health,
doi:10.3389/fpubh.2020.00186Bili Ński, Winter, Jasi Ński, Szczęś, Bilinska et al., Rapid resolution of COVID-19 after faecal microbiota transplantation, Gut,
doi:10.1136/gutjnl-2021-325010Carneiro, Littlefield, Watson, Palmer, Lozupone, Inflammation-associated gut microbiome in postacute sequelae of SARS-CoV-2 points towards new therapeutic targets, Gut,
doi:10.1136/gutjnl-2022-328757Ceccarelli, Borrazzo, Pinacchio, Santinelli, Innocenti et al., Oral Bacteriotherapy in Patients With COVID-19: A Retrospective Cohort Study, Front. Nutr,
doi:10.3389/fnut.2020.613928Cheng, Zhang, Li, Wu, Wu et al., Meta-analysis of 16S rRNA microbial data identified alterations of the gut microbiota in COVID-19 patients during the acute and recovery phases, BMC Microbiol,
doi:10.1186/s12866-022-02686-9Davani-Davari, Negahdaripour, Karimzadeh, Seifan, Mohkam et al., Prebiotics: Definition, Types, Sources, Mechanisms, and Clinical Applications, Foods,
doi:10.3390/foods8030092De Nies, Galata, Martin-Gallausiaux, Despotovic, Busi et al., Altered infective competence of the human gut microbiome in COVID-19, Microbiome,
doi:10.1186/s40168-023-01472-7Din, Mazhar, Waseem, Ahmad, Bibi et al., SARS-CoV-2 microbiome dysbiosis linked disorders and possible probiotics role, Biomed Pharmacother. Biomed. Pharmacother,
doi:10.1016/j.biopha.2020.110947Gaibani, D'amico, Bartoletti, Lombardo, Rampelli et al., The Gut Microbiota of Critically Ill Patients With COVID-19, Front. Cell Infect. Microbiol,
doi:10.3389/fcimb.2021.670424Gentilotti, Górska, Tami, Gusinow, Mirandola et al., Clinical phenotypes and quality of life to define post-COVID-19 syndrome: A cluster analysis of the multinational, prospective ORCHESTRA cohort, EClinicalMedicine,
doi:10.1016/j.eclinm.2023.102107Gutiérrez-Castrellón, Gandara-Martí, Abreu Yabreu, Nieto-Rufino, López-Orduña et al., Probiotic improves symptomatic and viral clearance in Covid19 outpatients: A randomized, quadruple-blinded, placebo-controlled trial, Gut Microbes,
doi:10.1080/19490976.2021.2018899Hegazy, Ahmed Ashoush, Tharwat Hegazy, Wahba, Lithy et al., Beyond probiotic legend: ESSAP gut microbiota health score to delineate SARS-COV-2 infection severity, Br. J. Nutr,
doi:10.1017/S0007114521001926Hill, Guarner, Reid, Gibson, Merenstein et al., The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic, Nat. Rev. Gastroenterol. Hepatol,
doi:10.1038/nrgastro.2014.66Hu, Zhang, Lin, Tang, Chan et al., Review article: Probiotics, prebiotics and dietary approaches during COVID-19 pandemic, Trends Food Sci. Technol,
doi:10.1016/j.tifs.2020.12.009Huang, Huang, Wang, Li, Ren et al., 6-month consequences of COVID-19 in patients discharged from hospital: A cohort study, Lancet Lond. Engl,
doi:10.1016/S0140-6736(20)32656-8Huerta-Cepas, Serra, Bork, ETE 3: Reconstruction, Analysis, and Visualization of Phylogenomic Data, Mol. Biol. Evol,
doi:10.1093/molbev/msw046Huson, Beier, Flade, Górska, El-Hadidi et al., MEGAN Community Edition-Interactive Exploration and Analysis of Large-Scale Microbiome Sequencing Data, PLoS Comput. Biol,
doi:10.1371/journal.pcbi.1004957Johnson, Hage, Kalveram, Mears, Plante et al., Peptidoglycan-Associated Cyclic Lipopeptide Disrupts Viral Infectivity, J. Virol,
doi:10.1128/JVI.01282-19Jones, Oliphant, Peterson, SciPy: Open Source Scientific Tools for Python
Kim, Joo, Lee, Ahn, Kim et al., Reversion of Gut Microbiota during the Recovery Phase in Patients with Asymptomatic or Mild COVID-19: Longitudinal Study, Microorganisms,
doi:10.3390/microorganisms9061237Kim, Kim, Kim, Gut microbiota restoration through fecal microbiota transplantation: A new atopic dermatitis therapy, Exp. Mol. Med,
doi:10.1038/s12276-021-00627-6Liu, Mak, Su, Yeoh, Lui et al., Gut microbiota dynamics in a prospective cohort of patients with post-acute COVID-19 syndrome, Gut,
doi:10.1136/gutjnl-2021-325989Liu, Su, Zhang, Tun, Mak et al., Multi-kingdom gut microbiota analyses define COVID-19 severity and post-acute COVID-19 syndrome, Nat. Commun,
doi:10.1038/s41467-022-34535-8Liu, Ye, Zhu, He, Wang et al., Gastrointestinal disturbance and effect of fecal microbiota transplantation in discharged COVID-19 patients, J. Med. Case Rep,
doi:10.1186/s13256-020-02583-7Mazzarelli, Giancola, Farina, Marchioni, Rueca et al., 16S rRNA gene sequencing of rectal swab in patients affected by COVID-19, PLoS ONE,
doi:10.1371/journal.pone.0247041Moreira-Rosário, Marques, Pinheiro, Araújo, Ribeiro et al., Gut Microbiota Diversity and C-Reactive Protein Are Predictors of Disease Severity in COVID-19 Patients, Front. Microbiol,
doi:10.3389/fmicb.2021.705020Newsome, Gauthier, Hernandez, Abraham, Robinson et al., The gut microbiome of COVID-19 recovered patients returns to uninfected status in a minority-dominated United States cohort, Gut Microbes,
doi:10.1080/19490976.2021.1926840Oliva, Di Nardo, Ferrari, Mallardo, Rossi et al., Randomised clinical trial: The effectiveness of Lactobacillus reuteri ATCC 55730 rectal enema in children with active distal ulcerative colitis, Aliment. Pharmacol. Ther,
doi:10.1111/j.1365-2036.2011.04939.xParker, Wearsch, Veloo, Rodriguez-Palacios, The Genus Alistipes: Gut Bacteria With Emerging Implications to Inflammation, Cancer, and Mental Health, Front. Immunol,
doi:10.3389/fimmu.2020.00906Piscotta, Hoffmann, Choi, Small, Ashbrook et al., Metabolites with SARS-CoV-2 Inhibitory Activity Identified from Human Microbiome Commensals, Msphere,
doi:10.1128/mSphere.00711-21Quast, Pruesse, Yilmaz, Gerken, Schweer et al., The SILVA ribosomal RNA gene database project: Improved data processing and web-based tools, Nucleic Acids Res,
doi:10.1093/nar/gks1219Reinold, Farahpour, Fehring, Dolff, Konik et al., A Pro-Inflammatory Gut Microbiome Characterizes SARS-CoV-2 Infected Patients and a Reduction in the Connectivity of an Anti-Inflammatory Bacterial Network Associates With Severe COVID-19, Front. Cell Infect. Microbiol,
doi:10.3389/fcimb.2021.747816Righi, Lambertenghi, Gorska, Sciammarella, Ivaldi et al., Impact of COVID-19 and Antibiotic Treatments on Gut Microbiome: A Role for Enterococcus spp, Biomedicines,
doi:10.3390/biomedicines10112786Righi, Mirandola, Mazzaferri, Dossi, Razzaboni et al., Determinants of persistence of symptoms and impact on physical and mental wellbeing in Long COVID: A prospective cohort study, J. Infect,
doi:10.1016/j.jinf.2022.02.003Righi, Mirandola, Mazzaferri, Razzaboni, Zaffagnini et al., Long-Term Patient-Centred Follow-up in a Prospective Cohort of Patients with COVID-19, Infect. Dis. Ther,
doi:10.1007/s40121-021-00461-3Su, Lau, Liu, Chan, Ng, Post-acute COVID-19 syndrome and gut dysbiosis linger beyond 1 year after SARS-CoV-2 clearance, Gut,
doi:10.1136/gutjnl-2022-328319Takahashi, Tomita, Nishioka, Hisada, Nishijima, Development of a prokaryotic universal primer for simultaneous analysis of Bacteria and Archaea using next-generation sequencing, PLoS ONE,
doi:10.1371/journal.pone.0105592Vestad, Ueland, Lerum, Dahl, Holm et al., Respiratory dysfunction three months after severe COVID-19 is associated with gut microbiota alterations, J. Intern. Med,
doi:10.1111/joim.13458Wischmeyer, Tang, Ren, Bohannon, Ramirez et al., Efficacy of Probiotic Treatment as Post-Exposure Prophylaxis for COVID-19: A Double-Blind, Placebo Controlled Randomized Tria
Wong, Zhang, Ching, Mak, Huang et al., Effects of Gut Microbiome Modulation on Reducing Adverse Health Outcomes among Elderly and Diabetes Patients during the COVID-19 Pandemic: A Randomised, Double-Blind, Placebo-Controlled Trial (IMPACT Study), Nutrients,
doi:10.3390/nu15081982Yeoh, Zuo, Lui, Zhang, Liu et al., Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19, Gut,
doi:10.1136/gutjnl-2020-323020Zhang, Han, Li, Chen, Xie et al., Probiotics use is associated with improved clinical outcomes among hospitalized patients with COVID-19, Ther. Adv. Gastroenterol,
doi:10.1177/17562848211035670Zhang, Lau, Liu, Su, Chan et al., Gut microbiota in COVID-19: Key microbial changes, potential mechanisms and clinical applications, Nat. Rev. Gastroenterol. Hepatol,
doi:10.1038/s41575-022-00698-4Zhang, Xu, Mak, Chow, Lui et al., Gut microbiota-derived synbiotic formula (SIM01) as a novel adjuvant therapy for COVID-19: An open-label pilot study, J. Gastroenterol. Hepatol,
doi:10.1111/jgh.15796Zhang, Zhou, Ma, Chen, Tang et al., Gut Microbiota Dysbiosis Correlates With Long COVID-19 at One-Year After Discharge, J. Korean Med. Sci,
doi:10.3346/jkms.2023.38.e120Zhou, Zhang, Zhang, Ma, Wang, Linking the gut microbiota to persistent symptoms in survivors of COVID-19 after discharge, J. Microbiol,
doi:10.1007/s12275-021-1206-5Zuo, Zhan, Zhang, Liu, Tso et al., Alterations in Fecal Fungal Microbiome of Patients With COVID-19 During Time of Hospitalization until Discharge, Gastroenterology,
doi:10.1053/j.gastro.2020.06.048
