Restore Intestinal Barrier Integrity: An Approach for Inflammatory Bowel Disease Therapy

Abstract

The intestinal barrier maintained by various types of columnar epithelial cells, plays a crucial role in regulating the interactions between the intestinal contents (such as the intestinal microbiota), the immune system, and other components. Dysfunction of the intestinal mucosa is a significant pathophysiological mechanism and clinical manifestation of inflammatory bowel disease (IBD). However, current therapies for IBD primarily focus on suppressing inflammation, and no disease-modifying treatments specifically target the epithelial barrier. Given the side effects associated with chronic immunotherapy, effective alternative therapies that promote mucosal healing are highly attractive. In this review, we examined the function of intestinal epithelial barrier function and the mechanisms of behind its disruption in IBD. We illustrated the complex process of intestinal mucosal healing and proposed therapeutic approaches to promote mucosal healing strategies in IBD. These included the application of stem cell transplantation and organ-like tissue engineering approaches to generate new intestinal tissue. Finally, we discussed potential strategies to restore the function of the intestinal barrier as a treatment for IBD.

Keywords: inflammatory bowel disease; intestinal barrier; pathophysiology; treatment.

Figure 1

Illustration of the structure and functions of intestinal barrier. The intestinal barrier consists of a chemical barrier and a physical barrier. The epithelial cells form a physical barrier consisting of tight junction-associated proteins, including occludin, claudin; JAM: junctional adhesion molecule. These tight junction protein components close off the paracellular pathways and function as gates and fences. The mucus layer is a chemical barrier consisting of a dense inner layer and a lax outer layer that is essential for prevent invading microorganisms and the host. The skeleton that makes up the mucus layer is primarily MUC2. Immune cells are also involved in the immune response and host tolerance to external substances. Damage to the intestinal barrier leads to infiltration of intestinal microorganisms from the lumen into the lamina propria, inducing immune stress in host immune cells.

Figure 2

The molecule diverts a key signaling molecule away from the intercellular junctions that regulate the intestinal barrier, preventing the immune system from disrupting the barrier.

Figure 3

Possible therapeutic strategies to improve the intestinal barrier function.

Figure 4

(a) Structural and functional modulation of the intestinal epithelial barrier under IBD will provide new ideas for the development of therapies for such chronic diseases. (b) The cell junctions of intestinal epithelium are disrupted in inflammatory bowel disease, providing potential targets for treatment.