The Gut Microbiota and COVID-19 Severity

Written by: Nadia Siles
Edited by: Esther Melamed

For years now, we have known that our gut microbiota, the millions of microorganisms that inhabit our digestive tract, is primarily shaped by our diet, environment, and genes.  The numerous interactions between our microbiota and our body are complex and bidirectional, to say the least. And in the past decade, mounting evidence has shown that our gut microbiota influences our immune system, as there appears to be a back-and-forth relationship between the gut microbiota and immune homeostasis in our body.

Although SARS-CoV-2 primarily infects the lungs, there is also evidence that the virus can infect cells from the digestive tract. COVID-19 patients have also been shown to have altered gut microbiota, supporting the GI tract’s involvement.  In patients with severe COVID-19, the disease is partly caused by an abnormal immune response in fighting the infection.  With all of this in mind, researchers at the Chinese University of Hong Kong set out to investigate whether the composition of the gut microbiota is linked to disease severity; and whether perturbations to the composition of the gut microbiota resolve after recovery from the infection.

They found that the composition of the gut microbiota in hospitalized COVID-19 patients was correlated with plasma concentrations of cytokines, chemokines, and inflammatory markers. This result suggested that gut microbiota may play a role in modulating the immune response in COVID-19 and thus influencing disease severity and outcomes.  In the study, COVID-19 patients with depleted bacterial species (e.g. Bifidobacterium adolescentis, Eubacterium rectale, and Faecalibacterium prausnitzii), known to reduce the inflammatory response in other inflammatory-related diseases, were associated with elevated concentrations of inflammatory cytokines and markers, such as CXCL10, IL-10, TNF-α, AST, GGT, CRP, LDH, NT-proBNP and erythrocyte sedimentation rates. In addition, there was an enrichment of bacterial species (such as Ruminococcus gnavus, Ruminococcus torques, Bacteroides dorei, and Bacteroides vulgatus) known to be prevalent in inflammatory gut diseases such as IBS and ulcerative colitis.  However, it is unclear whether these inflammatory-associated microorganisms play an active role in causing the disease or whether enrichment is a result of less competition for resources from other species.  Nevertheless, these findings could be used to develop a microbiome-based risk profile to identify people with a higher risk of severe COVID-19 or multisystem inflammatory syndrome.

In addition to looking at the gut microbiota of COVID-19 patients during their hospitalization, the researchers surveyed a small subset of these patients 30 days after they had cleared the infection and found that their gut microbiota remained significantly altered.  Compared to non-COVID-19 patients, the gut microbiota composition of COVID-19 patients had enrichment of Bifidobacterium dentium and Lactobacillus ruminis and depletion of E. rectale, R. bromii, F. prausnitzii, and Bifidobacterium longum. In light of recent reports on COVID-19 “long haulers” – recovered patients with persistent symptoms months after their initial onset of symptoms- the researchers suggest that dysbiotic gut microbiota in recovered COVID-19 patients could be contributing to these ongoing health problems.

The researchers acknowledged several limitations to their study, such as the variability in treatment modalities and inadequate representation of some disease severity groups. They also acknowledge the possibility that the gut microbiota composition may be a result of a patient’s health and immune state rather than directly playing a role in causing disease severity. Lastly, they caution that gut microbiota composition varies greatly across human populations and that these findings may not hold for COVID-19 patients from other geographies and cultures.  

This study emphasizes the need to investigate further the role our gut microbiota plays in our immune function. Future research on this topic could help us determine whether probiotic supplementation could help mitigate severe disease in COVID-19 patients and other inflammatory disorders, as well as inform us on how diet could play a role in COVID-19 and post-COVID syndrome.