Association between Gut Microbiota and SARS-CoV-2 Infection and Vaccine Immunogenicity

Abstract

Gut microbiota is increasingly recognized to play a pivotal role in various human physiological functions and diseases. Amidst the COVID-19 pandemic, research has suggested that dysbiosis of the gut microbiota is also involved in the development and severity of COVID-19 symptoms by regulating SARS-CoV-2 entry and modulating inflammation. Previous studies have also suggested that gut microbiota and their metabolites could have immunomodulatory effects on vaccine immunogenicity, including influenza vaccines and oral rotavirus vaccines. In light of these observations, it is possible that gut microbiota plays a role in influencing the immune responses to COVID-19 vaccinations via similar mechanisms including effects of lipopolysaccharides, flagellin, peptidoglycan, and short-chain fatty acids. In this review, we give an overview of the current understanding on the role of the gut microbiota in COVID-19 manifestations and vaccine immunogenicity. We then discuss the limitations of currently published studies on the associations between gut microbiota and COVID-19 vaccine outcomes. Future research directions shall be focused on the development of microbiota-based interventions on improving immune response to SARS-CoV-2 infection and vaccinations.

Keywords: COVID-19; COVID-19 vaccine; gut dysbiosis; gut microbiota; vaccine immunogenicity.

Figure 1

Potential mechanisms underlying the effect of gut microbiota on SARS-CoV-2 infection and vaccine immunogenicity. The gut microbiota and its metabolites, particularly those with immunomodulatory properties, can influence both the manifestations of COVID-19 and vaccine immunogenicity. In the context of COVID-19, dysbiosis of the gut microbiota may increase the severity of inflammation and various symptoms through modulating ACE2 expression in enterocytes and altered secretion of immunomodulatory molecules, such as tryptophan, SCFAs and secondary bile acids. Dysbiosis may potentially contribute to the production of cytokine storms, which produce more severe symptoms. In the long run, dysbiosis may be associated with persistent COVID-19 symptoms and inflammation, termed as post-acute COVID-19 syndrome (PACS). In the context of vaccine immunogenicity, lipopolysaccharides (LPSs), flagellin, peptidoglycan, and SCFAs secreted by the gut microbiota can enhance antibody production to vaccination by plasma B cells, thereby improving vaccine immunogenicity. Abbreviations: ACE2, angiotensin-converting enzyme 2; LPS, lipopolysaccharide; NOD2, nucleotide-binding oligomerization domain-containing protein 2; TLR-4, Toll-like receptor 4; TLR-5, Toll-like receptor 5; SCFA, short-chain fatty acid; NF-κB, nuclear factor-κB; Th17, T helper 17 cells; Treg, regulatory T cells.