Gut-lung axis and dysbiosis in COVID-19

Busra Aktas, Belma Aslim, Busra Aktas, Belma Aslim

Abstract

COVID-19, a novel infectious disease, caused by SARS-CoV-2, affected millions of people around the world with a high mortality rate. Although SARS-CoV-2 mainly causes lung infection, gastrointestinal symptoms described in COVID-19 patients and detection of the viral RNA in feces of infected patients drove attentions to a possible fecal-oral transmission route of SARS-CoV-2. However, not only the viral RNA but also the infectious viral particles are required for the viral infection and no proof has been demonstrated the transmission of the infectious virus particles via the fecal-oral route yet. Growing evidence indicates the crosstalk between gut microbiota and lung, that maintains host homeostasis and disease development with the association of immune system. This gut-lung interaction may influence the COVID-19 severity in patients with extrapulmonary conditions. Severity of COVID-19 has mostly associated with old ages and underlying medical conditions. Since the diversity in the gut microbiota decreases during aging, dysbiosis could be the reason for older adults being at high risk for severe illness from COVID-19. We believe that gut microbiota contributes to the course of COVID-19 due to its bidirectional relationship with immune system and lung. Dysbiosis in gut microbiota results in gut permeability leading to secondary infection and multiple organ failure. Conversely, disruption of the gut barrier integrity due to dysbiosis may lead to translocation of SARS-CoV-2 from the lung into the intestinal lumen via circulatory and lymphatic system. This review points out the role of dysbiosis of the gut microbiota involving in sepsis, on the severity of SARS-CoV-2 infection. Additionally, this review aims to clarify the ambiguity in fecal-oral transmission of SARS- CoV-2.

Keywords: COVID-19; dysbiosis; gut permeability; gut-lung axis.

Conflict of interest statement

CONFLICT OF INTEREST: none declared

Copyright © 2020 The Author(s).

Figures

Figure 1
Figure 1
Schematic illustration of gut-lung axis involving in COVID-19 severity with the association of dysbiosis.

References

    1. Aleman FDD Valenzano DR Microbiome evolution during host aging. PLoS Pathogens. 2019;15:21.
    1. Bäckhed F Ding H Wang T Hooper LV Koh GY The gut microbiota as an environmental factor that regulates fat storage. Proceedings of the National Academy of Sciences of the USA. 2004;101:15718.
    1. Bajaj JS Altered microbiota in cirrhosis and its relationship to the development of infection. Clinical Liver Disease. 2019;14:107.
    1. Bertók L Bile acids in physico-chemical host defence. Pathophysiology. 2004;11:139.
    1. Burcelin R Garidou L Pomié C Immuno-microbiota cross and talk: The new paradigm of metabolic diseases. Seminars in Immunology. 2012;24:67.
    1. Chen N Zhou M Dong X Qu J Gong F Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The Lancet. 2020;395:507.
    1. Chen Y Chen L Deng Q Zhang G Wu K The presence of SARS-CoV-2 RNA in the feces of COVID-19 patients. Journal of Medical Virology. 2020;31:1.
    1. D’Amico F Baumgart DC Danese S Peyrin-Biroulet L Diarrhea during COVID-19 infection: pathogenesis, epidemiology, prevention and management. Clinical Gastroenterology and Hepatology. doi: 10. 2020;04
    1. Darnell MER Subbarao K Feinstone SM Taylor DR Inactivation of the coronavirus that induces severe acute respiratory syndrome, SARS-CoV. Journal of Virological Methods. 2004;121:85.
    1. Deitch EA Gut-origin sepsis: Evolution of a concept. Surgeon. 2012;10:350.
    1. Dickson RP Singer BH Newstead MW Falkowski NR Erb-Downward JR Enrichment of the lung microbiome with gut bacteria in sepsis and the acute respiratory distress syndrome. Nature Microbiology. 2017;1:16113–16113.
    1. Ding S Liang TJ Is SARS-CoV-2 also an enteric pathogen with potential fecal-oral transmission: A COVID-19 virological and clinical review. Gastroenterology. doi: 10. 2020;04
    1. Doig CJ Sutherland LR Sandham JD Fick GH Verhoef M Increased intestinal permeability is associated with the development of multiple organ dysfunction syndrome in critically ill ICU patients. Pneumologie. 1998;52:441.
    1. Elfiky AA Anti-HCV, nucleotide inhibitors. repurposing against COVID-19. Life Sciences. 2020;248
    1. Fanos V Pintus MC Pintus R Marcialis MA Lung microbiota in the acute respiratory disease: from coronavirus to metabolomics. Journal of Pediatric and Neonatal Individualized Medicine. 2020;9:90139–90139.
    1. Feng G Zheng KI Yan Q-Q Rios RS Targher G COVID-19 and liver dysfunction: current insights and emergent therapeutic strategies. Journal of Clinical and Translational Hepatology. 2020;8:18.
    1. Gill SR Pop M Deboy RT Eckburg PB Turnbaugh PJ Metagenomic analysis of the human distal gut microbiome. Science. 2006;312:1355.
    1. Gu J Gong E Zhang B Zheng J Gao Z Multiple organ infection and the pathogenesis of SARS. Journal of Experimental Medicine. 2005;202:415.
    1. Guan WJ Ni ZY Hu Y Liang WH Ou CQ Clinical characteristics of coronavirus disease 2019 in China. New England Journal of Medicine. 2020;382:1708.
    1. Hanada S Pirzadeh M Carver KY Deng JC ( Frontiers in Immunology. 2018;9:1.
    1. Hickson M Probiotics in the prevention of antibiotic-associated diarrhoea and Clostridium difficile infection. Therapeutic Advances in Gastroenterology. 2011;4:185.
    1. Hilgenfeld R Peiris M From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses. Antiviral Research. 2013;100:286.
    1. Holshue ML DeBolt C Lindquist S Lofy KH Wiesman J First case of 2019 novel coronavirus in the United States. New England Journal of Medicine. 2020;382:929.
    1. Huang C Wang Y Li X Ren L Zhao J Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497.
    1. Hufnagl K Pali-Schöll I Roth-Walter F Jensen-Jarolim E Dysbiosis of the gut and lung microbiome has a role in asthma. Seminars in Immunopathology. 2020;42:75.
    1. Population-level COVID-19 mortality risk for non-elderly individuals overall and for non-elderly individuals without underlying diseases in pandemic epicenters. medRxiv. doi: 10. 2020.
    1. Kalantar-Zadeh K Ward SA Kalantar-Zadeh K El-Omar EM Considering the effects of microbiome and diet on SARS-CoV-2 infection: Nanotechnology roles. ACS Nano. 2020;14:5179.
    1. Keely S Talley NJ Hansbro PM Pulmonary-intestinal cross-talk in mucosal inflammatory disease. Mucosal Immunology. 2012;5:7.
    1. Li CK Wu H Yan H Ma S Wang L T Cell responses to whole SARS coronavirus in humans. Journal of Immunology. 2008;181:5490.
    1. Li X Geng M Peng Y Meng L Lu S Molecular immune pathogenesis and diagnosis of COVID-19. Journal of Pharmaceutical Analysis. 2020;10:102.
    1. Liang W Feng Z Rao S Xiao C Xue X Diarrhoea may be underestimated: A missing link in 2019 novel coronavirus. Gut. 2020;69:1141.
    1. Lin L Jiang X Zhang Z Huang S Gastrointestinal symptoms of 95 cases with SARS-CoV-2 infection. Gut. 2020;69:997.
    1. Mahase E Coronavirus covid-19 has killed more people than SARS and MERS combined, despite lower case fatality rate. BMJ. 2020;368
    1. Minemura M Shimizu Y Gut microbiota and liver disease. World Journal of Gastroenterol. 2015;21:1691.
    1. Ostaff MJ Stange EF Wehkamp J Antimicrobial peptides and gut microbiota in homeostasis and pathology. EMBO Molecular Medicine. 2013;5:1.
    1. Pan L Mu M Yang P Sun Y Wang R Clinical characteristics of COVID-19 patients with digestive symptoms in Hubei, China: A descriptive, cross-sectional, multicenter study. The American Journal of Gastroenterology. 2020;115:766.
    1. The SARS, MERS and novel coronavirus (COVID-19) epidemics, the newest and biggest global health threats: what lessons have we learned? International Journal of Epidemiology. doi: 10. 2020.
    1. Pratelli A Canine coronavirus inactivation with physical and chemical agents. Veterinary Journal. 2008;177:71.
    1. Proctor LM The human microbiome project in 2011 and beyond. Cell Host and Microbe. 2011;10:287.
    1. Roussos A Koursarakos P Patsopoulos D Gerogianni I Philippou N Increased prevalence of irritable bowel syndrome in patients with bronchial asthma. Respiratory Medicine. 2003;97:75.
    1. Ruan Q Yang K Wang W Jiang L Song J Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Medicine. 2020;46:846.
    1. Rutten EPA Lenaerts K Buurman WA Wouters EFM Disturbed intestinal integrity in patients with COPD: Effects of activities of daily living. Chest. 2014;145:245.
    1. Salazar N Valdés-Varela L González S Gueimonde M CG Nutrition and the gut microbiome in the elderly. Gut Microbes. 2017;8:82.
    1. Schrezenmeir J de Vrese M Probiotics, prebiotics, and synbiotics-approaching a definition. American Journal of Clinical Nutrition. 2001;73:361S.
    1. Song Y Liu P Shi XL Chu YL Zhang J SARS- CoV-2 induced diarrhoea as onset symptom in patient with. COVID-19. Gut. 2020;69:1143.
    1. Stability of the COVID-19 virus under wet, dry and acidic conditions. medRxiv. doi: 10. 2020.
    1. Tai N Wong FS Wen L The role of gut microbiota in the development of type 1, type 2 diabetes mellitus and obesity. Reviews in Endocrine and Metabolic Disorders. 2015;16:55.
    1. Vrieze A Van Nood E Holleman F Salojärvi J Kootte RS Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012;143:913.
    1. Wan Y Shang J Graham R Baric RS Li F Receptor recognition by the novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS coronavirus. Journal of Virology. 2020;94:1.
    1. Wang D Hu B Hu C Zhu F Liu X Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA - Journal of the American Medical Association. 2020;323:1061.
    1. Wang H Ma S The cytokine storm and factors determining the sequence and severity of organ dysfunction in multiple organ dysfunction syndrome. American Journal of Emergency Medicine. 2008;26:711.
    1. Wang J Li F Wei H Lian ZX Sun R Respiratory influenza virus infection induces intestinal immune injury via microbiotamediated Th17 cell-dependent inflammation. Journal of Experimental Medicine. 2014;211:2397.
    1. Fecal-Oral Transmission. 2017. p. 400.
    1. Consensus document on the epidemiology of severe acute respiratory syndrome (SARS) 2003.
    1. General’s opening remarks at the media briefing on COVID-19 2020.
    1. Wu A Peng Y Huang B Ding X Wang X Genome composition and divergence of the novel coronavirus (2019-nCoV) originating in China. Cell Host and Microbe. 2020;27:325.
    1. Wu F Zhao S Yu B Chen YM Wang W A new coronavirus associated with human respiratory disease in China. Nature. 2020;579:265.
    1. Wu YC Chen CS Chan YJ The outbreak of COVID-19: An overview. Journal of the Chinese Medical Association. 2020;83:217.
    1. Wu Y Guo C Tang L Hong Z Zhou J Prolonged presence of SARS-CoV-2 viral RNA in faecal samples. Lancet Gastroenterology and Hepatology. 2020;5:434.
    1. Xiao F Tang M Zheng X Liu Y Li X Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology. 2020;158:1831.
    1. Xu PP Tian RH Luo S Zu ZY Fan B Risk factors for adverse clinical outcomes with COVID-19 in China: A multicenter, retrospective, observational study. Theranostics. 2020;10:6372.
    1. Zang R Castro MFG McCune BT Zeng Q Rothlauf PW TMPRSS2 and TMPRSS4 mediate SARS-CoV-2 infection of human small intestinal enterocytes. Science Immunology. 2020;5
    1. Zhang H Kang Z Gong H Xu D Wang J Digestive system is a potential route of COVID-19: An analysis of single-cell coexpression pattern of key proteins in viral entry process. Gut. 2020;69:1010.
    1. Zhang J-J Dong X Cao Y-Y Yuan Y-D Yang Y Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. 2020;10
    1. Detectable SARS-CoV-2 viral RNA in feces of three children during recovery period of COVID-19 pneumonia. Journal of Medical Virology. doi: 10. 2020.
    1. Zhang Y Chen C Zhu S Shu C Wang D Notes from the field isolation of 2019-nCoV from a stool specimen of a laboratory- confirmed case of the coronavirus disease 2019 ( COVID-19 ) China CDC Weekly. 2020;2:2019.
    1. Zheng M Gao Y Wang G Song G Liu S Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cellular and Molecular Immunology. 2020;17:533.
    1. Zhu N Zhang D Wang W Li X Yang B A novel coronavirus from patients with pneumonia in China, 2019. New England Journal of Medicine. 2020;382:727.

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