Crosstalk Between the Gut Microbiota and Epithelial Cells Under Physiological and Infectious Conditions

Abstract

The gastrointestinal tract (GIT) is considered the largest immunological organ, with a diverse gut microbiota, that contributes to combatting pathogens and maintaining human health. Under physiological conditions, the crosstalk between gut microbiota and intestinal epithelial cells (IECs) plays a crucial role in GIT homeostasis. Gut microbiota and derived metabolites can compromise gut barrier integrity by activating some signaling pathways in IECs. Conversely, IECs can separate the gut microbiota from the host immune cells to avoid an excessive immune response and regulate the composition of the gut microbiota by providing an alternative energy source and releasing some molecules, such as hormones and mucus. Infections by various pathogens, such as bacteria, viruses, and parasites, can disturb the diversity of the gut microbiota and influence the structure and metabolism of IECs. However, the interaction between gut microbiota and IECs during infection is still not clear. In this review, we will focus on the existing evidence to elucidate the crosstalk between gut microbiota and IECs during infection and discuss some potential therapeutic methods, including probiotics, fecal microbiota transplantation (FMT), and dietary fiber. Understanding the role of crosstalk during infection may help us to establish novel strategies for prevention and treatment in patients with infectious diseases, such as C. difficile infection, HIV, and COVID-19.

Keywords: COVID-19; epithelial cells; gut microbiota; infection; probiotics.

Figure 1

Crosstalk between the gut microbiota and IECs under physiological conditions. In physiological conditions, the components of the gut microbiota and derived metabolites compromise or destroy intestinal barrier integrity through different pathways, such as mTOR, AhR, FXR and TLR. For instance, SCFAs promote the production of RegIIIγ and defensins from IECs by activating mTOR. The activation of SCFAs and indole can improve the function of tight junctions. The components of the gut microbiota, such as LPS, promote the production of antimicrobial molecules in IECs. On the other hand, secondary bile acids from gut microbiota may inhibit the repair of the gut barrier. Conversely, IECs can modulate the composition of gut microbiota by providing some signaling molecules or alternative energy resources, including AMPs, hormones, and mucins.

Figure 2

Crosstalk between the gut microbiota and IECs during infection. Bacterial infection, viral infection and parasite infection can induce dysbiosis of the gut microbiota and impairment of the gut barrier. The crosstalk between the gut microbiota and IECs may play an essential role during infection. For instance, the gut microbiota regulates the response to pathogens in IECs by modulating the expression of SPRR2A, RA, and HIF-1. IECs can alter the composition of gut microbiota and contribute to protection against infections.

Figure 3

Underlying prevention and therapeutic strategies for infection. Some underlying prevention or therapeutic strategies, such as probiotics, FMT, and dietary fiber, can directly suppress pathogens, modulate the diversity of the gut microbiota, and maintain the integrity of the intestinal barrier during infection.