Abstract
BackgroundCOVID-19 is an infectious disease characterized by multiple respiratory and extrapulmonary manifestations, including gastrointestinal symptoms. Although recent studies have linked gut microbiota to infectious diseases such as influenza, little is known about the role of the gut microbiota in COVID-19 pathophysiology.MethodsTo better understand the host-gut microbiota interactions in COVID-19, we characterized the gut microbial community and gut barrier function using metagenomic and metaproteomic approaches in 63 COVID-19 patients and 8 non-infected controls. Both immunohematological parameters and transcriptional profiles were measured to reflect the immune response in COVID-19 patients.ResultsAltered gut microbial composition was observed in COVID-19 patients, which was characterized by decreased commensal species and increased opportunistic pathogenic species. Severe illness was associated with higher abundance of four microbial species (i.e., Burkholderia contaminans, Bacteroides nordii, Bifidobacterium longum, and Blautia sp. CAG 257), six microbial pathways (e.g., glycolysis and fermentation), and 10 virulence genes. These severity-related microbial features were further associated with host immune response. For example, the abundance of Bu. contaminans was associated with higher levels of inflammation biomarkers and lower levels of immune cells. Furthermore, human-origin proteins identified from both blood and fecal samples suggested gut barrier dysfunction in COVID-19 patients. The circulating levels of lipopolysaccharide-binding protein increased in patients with severe illness and were associated with circulating inflammation biomarkers and immune cells. Besides, proteins of disease-related bacteria (e.g., B. longum) were detectable in blood samples from patients.ConclusionsOur results suggest that the dysbiosis of the gut microbiome and the dysfunction of the gut barrier might play a role in the pathophysiology of COVID-19 by affecting host immune homeostasis.
Highlights
COVID-19 is an infectious disease characterized by multiple respiratory and extrapulmonary manifestations, including gastrointestinal symptoms
The infection of SARS-CoV-2 could impair the normal expression of angiotensin-converting enzyme 2 (ACE2), which might result in several adverse outcomes, including GI symptoms as well as the dysbiosis of gut microbiota [6]
Gut microbiome in COVID-19 patients To better understand the effect of SARS-CoV-2 infection on the gut microbiome, we studied the gut microbial communities of COVID-19 patients, by using metagenomic sequencing in 106 fecal samples collected serially from COVID-19 patients and noninfected controls (Additional file 1: Fig. S2 and Additional file 2: Table S2)
Summary
COVID-19 is an infectious disease characterized by multiple respiratory and extrapulmonary manifestations, including gastrointestinal symptoms. Recent studies have linked gut microbiota to infectious diseases such as influenza, little is known about the role of the gut microbiota in COVID-19 pathophysiology. Coronavirus disease 2019 (COVID-19), caused by a novel beta-coronavirus (severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)), has been a global pandemic and caused more than five million deaths worldwide until November of 2021 [1]. Altered gut microbiota was observed among patients with a wide range of infectious diseases, including influenza and other respiratory viral infections [14,15,16,17]. Recent studies described the alterations in the gut microbial composition of COVID-19 patients, characterized by enrichment of opportunistic pathogens and depletion of beneficial commensals [18,19,20]. The potential mechanism underlying the associations between the gut microbiome and COVID-19 severity remains to be explored
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