The Association Between the Gut Microbiome and COVID-19 Severity: The Potential Role of TMAO Produced by the Gut Microbiome

Context: The COVID-19 pandemic has had profound impacts on public health, resulting in nearly 1 million deaths. Emerging evidence suggests an association between certain metabolites produced by gut microbiota and potential alterations in the severity of infection. Trimethylamine N-oxide (TMAO) is a waste metabolite generated by gut microbes from dietary choline and betaine. Evidence Acquisition: Several investigations have indicated an association between serum TMAO concentrations and the development of inflammation and thrombosis. Trimethylamine N-oxide, produced by the gut microbiome in a state of dysbiosis, upregulates various molecular mechanisms, such as the nuclear factor kappa (NF-kB) molecular pathway, and promotes the expression of scavenger receptors (SRs) on the surfaces of macrophages, leading to foam cell formation and inflammation. High levels of TMAO have been shown to induce the expression of pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α) and interleukin 1β (IL-1β) while reducing the expression of anti-inflammatory cytokines such as interleukin-10 (IL-10). Additionally, gut-derived TMAO enhances platelet aggregation and adhesion to collagen, increasing the risk of thrombosis. Conclusions: Understanding the association between gut microbiome compositions such as gut TMAO and their effects on SARS-CoV-19 infection progression helps to control disease severity. In this review, we presented a hypothesis that the gut TMAO has the potential to increase COVID-19 disease severity.