Published in 'Gut', the study found that associations between gut microbiota composition, levels of cytokines and inflammatory markers in patients with COVID-19 suggest that the gut microbiome is involved in COVID-19 severity possibly via modulating host immune responses.
The researchers also suggest the gut microbiota dysbiosis after disease resolution could contribute to persistent symptoms, aka 'long COVID', highlighting a need to understand how gut microorganisms are involved in inflammation and COVID-19.
The researchers, from the Chinese University of Hong Kong, collected blood and stool samples from 100 patients with COVID-19 between February and May 2020. In total, 274 stool samples were sequenced.
In identifying microbial species associated with disease severity, they found that F. prausnitzii and Bifidobacterium bifidum were negatively correlated with severity after adjusting for antibiotic use and patients’ age. The numbers of these bacteria remained low in the samples collected up to 30 days after infected patients had cleared the virus from their bodies.
The report states: "The potential role played by gut microorganisms in COVID-19 could allow the use of a microbiome-based risk profile to identify individuals at risk of severe disease or downstream inflammatory symptoms such as multisystem inflammation and Kawasaki-like disease in children.
"Based on several patients surveyed in this study for up to 30 days after clearing SARS-CoV-2, the gut microbiota is likely to remain significantly altered after recovery from COVID-19. In light of reports that a subset of recovered patients with COVID-19 experience persistent symptoms such as fatigue, dyspnoea and joint pains, some over 80 days after initial onset of symptoms, we posit that the dysbiotic gut microbiome could contribute to immune-related health problems post-COVID-19."
The study
First, the researchers compared gut microbiota compositions of the first stool samples of each COVID-19 patient (n=87) with non-COVID-19 subjects (45 women to 33 men, 45.5±17.4 years old) to assess whether gut microbiota composition was altered.
They found that members of the Bacteroidetes were more relatively abundant in patients with COVID-19 compared with non-COVID-19 individuals (mean 23.9% vs 12.8%), whereas Actinobacteria were more relatively abundant in non-COVID-19 individuals (26.1% vs 19.0%).
Without controlling for use of antibiotics, compositional differences in the gut microbiota of COVID-19 were primarily driven by enrichment of species including Ruminococcus gnavus, Ruminococcus torques and Bacteroides dorei and depletion of Bifidobacterium adolescentis, Faecalibacterium prausnitzii and Eubacterium rectale.
When antibiotic effects were examined, differences between cohorts were primarily linked to enrichment of taxa such as Parabacteroides, Sutterella wadsworthensis and Bacteroides caccae and depletion of Adlercreutzia equolifaciens, Dorea formicigenerans and Clostridium leptum in COVID-19 relative to non-COVID-19, although most of the implicated taxa comprised less than 0.1% average relative abundance in these samples.
While the overall gut microbiota composition was distinct between the 87 COVID-19 and 78 non-COVID-19 subjects, there were no significant differences in species richness and Shannon diversity.
The researchers note the observational nature of the study means they cannot establish cause and effect, and it's important to note the gut microbiome varies widely among different populations.
The also say their short follow-up period does not permit extrapolation of gut microbiota composition to long-term persistent symptoms.
The report states: "Longer follow-up of patients with COVID-19 (3 months to 1 year after clearing the virus) is needed to address questions related to the duration of gut microbiota dysbiosis postrecovery, link between microbiota dysbiosis and long-term persistent symptoms and whether the dysbiosis or enrichment/depletion of specific gut microorganisms predisposes recovered individuals to future health problems."
Source: Gut
doi: 10.1136/gutjnl-2020-323020
"Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19"
Siew. C. N., et al