Integrated gut virome and bacteriome dynamics in COVID-19 patients

Abstract

SARS-CoV-2 is the cause of the current global pandemic of COVID-19; this virus infects multiple organs, such as the lungs and gastrointestinal tract. The microbiome in these organs, including the bacteriome and virome, responds to infection and might also influence disease progression and treatment outcome. In a cohort of 13 COVID-19 patients in Beijing, China, we observed that the gut virome and bacteriome in the COVID-19 patients were notably different from those of five healthy controls. We identified a bacterial dysbiosis signature by observing reduced diversity and viral shifts in patients, and among the patients, the bacterial/viral compositions were different between patients of different severities, although these differences are not entirely distinguishable from the effect of antibiotics. Severe cases of COVID-19 exhibited a greater abundance of opportunistic pathogens but were depleted for butyrate-producing groups of bacteria compared with mild to moderate cases. We replicated our findings in a mouse COVID-19 model, confirmed virome differences and bacteriome dysbiosis due to SARS-CoV-2 infection, and observed that immune/infection-related genes were differentially expressed in gut epithelial cells during infection, possibly explaining the virome and bacteriome dynamics. Our results suggest that the components of the microbiome, including the bacteriome and virome, are affected by SARS-CoV-2 infections, while their compositional signatures could reflect or even contribute to disease severity and recovery processes.

Mild and Severe SARS-CoV-2 Infection Induces Respiratory and Intestinal Microbiome Changes in the K18-hACE2 Transgenic Mouse Model

“…2F and G ), further suggesting that microbial change is virus dose dependent. A similar relationship was previously observed among unvaccinated and vaccinated SARS-CoV-2-infected mice with a high dose ( 47 ). Analyzing the commensal microbiome in other diseases has shown that the microbiota can both regulate and be regulated by viral pathogens and facilitate stimulatory or suppressive effects on the host immune response ( 49 ).…”

“…These observations suggest a virus dose-dependent effect of the ceca microbial alpha diversity in mice infected with SARS-CoV-2. While preparing the manuscript, a report was published that analyzed the small intestine microbiome of hACE2 mice among unvaccinated and vaccinated mice challenged with a high dose of SARS-CoV-2 ( 47 ). While we compared control mice to nonvaccinated mice challenged with low and high doses of SARS-CoV-2 in this study, findings were similar, since a decrease in alpha diversity in the unvaccinated mice was reported, which was consistent with results obtained from human fecal samples ( 5 , 47 ).…”

“…While preparing the manuscript, a report was published that analyzed the small intestine microbiome of hACE2 mice among unvaccinated and vaccinated mice challenged with a high dose of SARS-CoV-2 ( 47 ). While we compared control mice to nonvaccinated mice challenged with low and high doses of SARS-CoV-2 in this study, findings were similar, since a decrease in alpha diversity in the unvaccinated mice was reported, which was consistent with results obtained from human fecal samples ( 5 , 47 ). From the beta diversity analysis, the weighted Bray-Curtis NMDS showed that samples from the high-virus-dose group were outliers compared to the rest of the samples, consistent with exacerbation of clinical signs and following peak virus replication in this group ( 40 , 43 , 44 , 48 ).…”

Gut Microbiota Dysbiosis and COVID-19: Possible Links

“…In general, COVID-19 infection enriches the opportunistic pathogens and lessens the populations commonly known as beneficial. Depletion in some bacterial groups, such as Faecalibacterium prausnitzii, Eubacterium rectale , and Collinsella aerofaciens were even higher in the COVID-19 patients using antibiotics during treatment, with a lower bacterial diversity ( Zuo et al., 2020 ; Cao et al., 2021 ; Yeoh et al., 2021 ). Alteration in the gut microbiota have been reported to be associated with COVID-19 severity and some of the populations, such as Faecalibacterium were negatively correlated with the disease severity while some of them, such as Coprobacillus correlated positively ( Zuo et al., 2020 ; Cao et al., 2021 ; Yeoh et al., 2021 ).…”

“…Depletion in some bacterial groups, such as Faecalibacterium prausnitzii, Eubacterium rectale , and Collinsella aerofaciens were even higher in the COVID-19 patients using antibiotics during treatment, with a lower bacterial diversity ( Zuo et al., 2020 ; Cao et al., 2021 ; Yeoh et al., 2021 ). Alteration in the gut microbiota have been reported to be associated with COVID-19 severity and some of the populations, such as Faecalibacterium were negatively correlated with the disease severity while some of them, such as Coprobacillus correlated positively ( Zuo et al., 2020 ; Cao et al., 2021 ; Yeoh et al., 2021 ). The severity of COVID-19 patients has been determined with an elevated level of inflammatory cytokines in blood or feces including IL-18, IL-10, TNF-α, C- X- C motif ligand (CXCL)8 and CXCL10, blood markers such as C reactive protein (CRP), lactate dehydrogenase, and natural killer cells ( Tang et al., 2020 ; Tao et al., 2020 ; Yeoh et al., 2021 ).…”