[1.4] - 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.
[1.5] - A disrupted gut microbiome (gut dysbiosis) can lead to epithelium breakdown and inflammation, which have been shown to increase levels of angiotensin-converting enzyme 2 (ACE2), the target of SARS-CoV-2.
- Increased gut permeability can lead to pro-inflammatory bacterial products to leak out and circulate systemically, triggering inflammatory cascades.
- A specific gut microbiota composition may predispose healthy individuals to severe COVID-19 infections; increased levels of pro-inflammatory bacterial species correlated with elevated levels of pro-inflammatory cytokines and increased disease severity.
- A disrupted gut microbiome may also contribute to increased pro-inflammatory cytokine production (“cytokine storm”), known to worsen severity of SARS-CoV-2 infection.
- Proteomic and metabolomic profiling has shown progression to severe COVID-19 infection can be predicted both in infected patients and in healthy individuals.
- Elderly and immunocompromised populations are known to have reduced microbiota diversity. Since many of these vulnerable patients have had worse clinical outcomes for COVID-19, this strengthens the possibility that the gut microbiome is affecting clinical progression.
- Reduced gut microbiome diversity may therefore be useful as a predictive biomarker of COVID-19 severity.
Mechanisms underpinning gastrointestinal symptoms are thought to involve ACE2 receptors, which are highly expressed on intestinal epithelial cells , in particular the brush border membrane of small intestinal enterocytes.
- ACE2 gene expression has been shown to increase with age, potentially accounting for differential susceptibility to more severe disease.