Journal Article

Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19

Liu, Qin, Ng, Siew C, Wong, Grace Lai-Hung, Cheung, Chun Pan, Li, Amy YL, Yip, Terry CF, Chan, Francis KL, Li, Timothy Chun-Man, Hui, David Shu-Cheong, Chung, Arthur CK, Ng, Rita WY, Tso, Eugene YK, Fung, Kitty SC, Chan, Veronica, Chow, Kai Ming, Zuo, Tao, Zhang, Fen, Wong, Chun Kwok, Yeoh, Yun Kit, Chan, Paul KS, Lui, Grace Chung-Yan, Ling, Lowell, Ng, Susanna So Shan, Joynt, Gavin

2021

Overview

ObjectiveAlthough COVID-19 is primarily a respiratory illness, there is mounting evidence suggesting that the GI tract is involved in this disease. We investigated whether the gut microbiome is linked to disease severity in patients with COVID-19, and whether perturbations in microbiome composition, if any, resolve with clearance of the SARS-CoV-2 virus.MethodsIn this two-hospital cohort study, we obtained blood, stool and patient records from 100 patients with laboratory-confirmed SARS-CoV-2 infection. Serial stool samples were collected from 27 of the 100 patients up to 30 days after clearance of SARS-CoV-2. Gut microbiome compositions were characterised by shotgun sequencing total DNA extracted from stools. Concentrations of inflammatory cytokines and blood markers were measured from plasma.ResultsGut microbiome composition was significantly altered in patients with COVID-19 compared with non-COVID-19 individuals irrespective of whether patients had received medication (p<0.01). Several gut commensals with known immunomodulatory potential such as Faecalibacterium prausnitzii, Eubacterium rectale and bifidobacteria were underrepresented in patients and remained low in samples collected up to 30 days after disease resolution. Moreover, this perturbed composition exhibited stratification with disease severity concordant with elevated concentrations of inflammatory cytokines and blood markers such as C reactive protein, lactate dehydrogenase, aspartate aminotransferase and gamma-glutamyl transferase.ConclusionAssociations between gut microbiota composition, levels of cytokines and inflammatory markers in patients with COVID-19 suggest that the gut microbiome is involved in the magnitude of COVID-19 severity possibly via modulating host immune responses. Furthermore, the gut microbiota dysbiosis after disease resolution could contribute to persistent symptoms, highlighting a need to understand how gut microorganisms are involved in inflammation and COVID-19.

• Publisher: BMJ Publishing Group Ltd and British Society of Gastroenterology,BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: Adult / Aspartate aminotransferase / Bacteria - genetics / Bacteria - immunology / Bacteria - isolation & purification / Blood / C-reactive protein / C-Reactive Protein - analysis / Chemokines / colonic bacteria / colonic microflora / Colonoscopy / Commensals / Coronaviruses / COVID-19 / COVID-19 - blood / COVID-19 - diagnosis / COVID-19 - epidemiology / COVID-19 - immunology / Cytokines / Cytokines - analysis / Deoxyribonucleic acid / Discriminant analysis / DNA / DNA sequencing / DNA, Bacterial - isolation & purification / Dysbacteriosis / Dysbiosis - epidemiology / Dysbiosis - etiology / Dysbiosis - immunology / Dysbiosis - virology / Feces / Female / Gastrointestinal Microbiome - immunology / Gastrointestinal tract / Gastrointestinal Tract - immunology / Gastrointestinal Tract - microbiology / Gastrointestinal Tract - virology / Gut Microbiota / Hong Kong / Humans / Hypertension / Immune clearance / Immune response / Immunity / Immunomodulation / Inflammation / Intestinal microflora / L-Lactate dehydrogenase / Laboratories / Lactic acid / Male / Microbiomes / Microbiota / Multivariate analysis / Pathophysiology / Patients / Plasma / Pneumonia / Principal components analysis / SARS-CoV-2 - immunology / SARS-CoV-2 - isolation & purification / Severe acute respiratory syndrome coronavirus 2 / Severity of Illness Index / Statistical analysis / Transferases - analysis / Viruses / γ-Glutamyltransferase