Intestinal Barrier Function in Health and Disease-Any role of SARS-CoV-2?

Abstract

Alterations in the structure and function of the intestinal barrier play a role in the pathogenesis of a multitude of diseases. During the recent and ongoing coronavirus disease (COVID-19) pandemic, it has become clear that the gastrointestinal system and the gut barrier may be affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, and disruption of barrier functions or intestinal microbial dysbiosis may have an impact on the progression and severity of this new disease. In this review, we aim to provide an overview of current evidence on the involvement of gut alterations in human disease including COVID-19, with a prospective outlook on supportive therapeutic strategies that may be investigated to rescue intestinal barrier functions and possibly facilitate clinical improvement in these patients.

Keywords: COVID-19; FMT; SARS-CoV-2; gastrointestinal; gut barrier; gut permeability; gut–liver axis; immune; microbiota; probiotics.

Figure 1

This figure outlines the key layers of the intestinal barrier. The mucus layer is composed of mucin proteins, but this layer also contains IgA antibodies, defensins and a proportion of the intestinal microbiota. The epithelial layer contains many specialized cell types, including enterocytes, microfold cells (M-cells) and Paneth cells, amoung others. The cells in this layer are connected by transmembrane protein complexes. The lamina propria is a connective tissue layer that contains immune cells, blood vessels and lymphatic vessels. Figure created with BioRender.com (accessed Aug 2020).

Figure 2

This figure illustrates how pathology can arise in the different layers of the gut barrier and highlights how examples of treatment strategies can ameliorate these pathological alterations. In pathology, there can be an alterations of mucus layer thickness. Probiotics have been shown to increase mucus layer thickness. Microbial dysbiosis can occur in disease and it is thought that probiotics, faecal microbiota transplantation (FMT) and dietary therapies can correct this dysbiosis. Tight junction alterations can also occur in disease and this has been associated with an increase in cytokines, an increase in zonulin and a decrease in short-chain fatty acids (SCFAs). Probiotics, FMT and dietary therapies could potentially reverse these changes by increasing the concentrations of SCFAs. In the figure, small arrows indicate increase or decrease, while the dotted arrows indicate the movement of bacterial matter as it translocates across the intestinal barrier. Figure created with BioRender.com (accessed on August 2020).

Figure 3

This figure delineates the link between SARS-CoV-2-related intestinal pathology and pathology associated with disruption of the gut–lung axis. Supportive treatment strategies to correct gut barrier alterations could potentially have a beneficial effect on rebalancing the gut–lung axis in COVID-19 patients. Figure created with BioRender.com.