Intestinal Flora as a Potential Strategy to Fight SARS-CoV-2 Infection

Abstract

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly worldwide, seriously endangering human health. In addition to the typical symptoms of pulmonary infection, patients with COVID-19 have been reported to have gastrointestinal symptoms and/or intestinal flora dysbiosis. It is known that a healthy intestinal flora is closely related to the maintenance of pulmonary and systemic health by regulating the host immune homeostasis. Role of the "gut-lung axis" has also been well-articulated. This review provides a novel suggestion that intestinal flora may be one of the mediators of the gastrointestinal responses and abnormal immune responses in hosts caused by SARS-CoV-2; improving the composition of intestinal flora and the proportion of its metabolites through probiotics, and personalized diet could be a potential strategy to prevent and treat COVID-19. More clinical and evidence-based medical trials may be initiated to determine the strategy.

Keywords: COVID-19; SARS-CoV-2; SCFAs; gut-lung axis; immunity; intestinal flora.

Figure 1

(A) Adverse effects of SARS-CoV-2 on the human lungs and intestine. SARS-CoV-2 can be transmitted through the respiratory or digestive tract, directly infecting the host by binding with the ACE2 receptor of pulmonary epithelial or intestinal epithelial cells. This leads to lung and/or intestinal tissue damage and a systemic immune response. However, after initially infecting the lungs, SARS-CoV-2 can break through the mucosal immune barrier and indirectly affect the intestine along the “gut-lung axis”, and vice versa. Intestinal tissue damage, an excessive inflammatory response, and a dysfunctional immune response can lead to intestinal microecological disorder. However, some interventions (e.g., probiotics, beneficial metabolites, and eliminating harmful bacteria) can provide resistance against these adverse effects. The “gut-lung axis” refers to the cross-talk between these two mucosal parts of the human body, which may take place via blood and lymphatic circulation. The yellow arrows represent “increased barrier dysfunction.” The red arrows represent “adverse effects of SARS-CoV-2 infection.” (B) Possible model for using probiotics and beneficial metabolites (e.g., short chain fatty acids; SCFAs) against lung infection and injury. Probiotics and metabolites such as SCFAs can be taken up by M cells and presented to T cells as antigens via dendritic cells, leading to T/B cell proliferation and activation. Guided by immune mediators, immune cells are then localized at the lung infection site, enhancing antiviral immunity, and providing protection to the lungs. The intestinal innate lymphoid cells (ILC2 and ILC3) can migrate to the lungs to enhance antiviral immunity via lymphatic and blood circulations (purple arrows). Surface IgA can be produced and transported from gut-associated lymphoid tissues to the surface of the pulmonary mucosa, which can prevent virus adhesion and consolidate the mucosal barrier. SCFAs produced by intestinal flora can be transported to the lungs through the blood, where they can play an anti-inflammatory role and consolidate the lung mucosal barrier (green arrows). SCFAs can also be transported to the bone marrow and enhance its hematopoietic function, further promoting the proliferation and activation of dendritic cells and other immune cells. Overall, these phenomena can enhance the antiviral immunity of the host (red arrows).