Biological Clock and Inflammatory Bowel Disease Review: From the Standpoint of the Intestinal Barrier

Abstract

Inflammatory bowel disease is a group of chronic, recurrent, nonspecific inflammatory diseases of the intestine that severely affect the quality of life of patients. The pathogenesis of this disease is caused by complex and interactive neural networks composed of factors such as genetic susceptibility, external environment, immune disorders, and intestinal barrier dysfunction. It is well known that there is a strong link between environmental stressors (also known as circadian clocks) that can influence circadian changes and inflammatory bowel disease. Among them, the biological clock is involved in the pathogenesis of inflammatory bowel disease by affecting the function of the intestinal barrier. Therefore, this review is aimed at systematically summarizing the latest research progress on the role of the circadian clock in the pathogenesis of inflammatory bowel disease by affecting intestinal barrier functions (intestinal mechanical barrier, intestinal immune barrier, intestinal microecological barrier, and intestinal chemical barrier) and the potential clinical value of clock genes in the management of inflammatory bowel disease, for the application of circadian clock therapy in the management of inflammatory bowel disease and then the benefit to the majority of patients.

Relationship between the Biological Clock and Inflammatory Bowel Disease

“…A critical part of the development of IBD is the stability and function of the intestinal barrier [ 70 , 71 , 72 , 73 ]. Tight junctions close gaps between epithelial cells to prevent the passage of inflammatory substances.…”

“…At the same time, intestinal inflammation has been reported to disrupt the biological clock. Previous analyses of the biological clock and IBD found strong relationships between the circadian clock, intestinal defense and the immune system [ 73 , 78 ].…”

The role of circadian clock in regulating cell functions: implications for diseases

“…Of particular note, BMAL1 plays a central role in the regulation of intestinal epithelial cell regeneration by modulating cytokine activity, cell cycle progression, and cell proliferation dynamics. It is worth highlighting that knockdown of Bmal1 results in the disruption of the rhythmic pattern of cellular proliferation 133,134 . Furthermore, TNF cytokine signaling and P21 emerge as key contributors to BMAL1‐mediated cell proliferation control.…”

Milk: A Natural Guardian for the Gut Barrier

“…Digestive secretions include gastric juice, bile, and other chemicals produced in the gastrointestinal tract. Gastric juice prevents bacterial aggregation and adhesion to the intestinal epithelium, whereas bile influences gastrointestinal peristalsis, intestinal barrier permeability, and inflammation . Antimicrobial peptides (AMPs) are integral components of innate immunity, including defensins and cathelicidins in mammals.…”

“…Gastric juice prevents bacterial aggregation and adhesion to the intestinal epithelium, whereas bile influences gastrointestinal peristalsis, intestinal barrier permeability, and inflammation. 25 Antimicrobial peptides (AMPs) are integral components of innate immunity, including defensins and cathelicidins in mammals. These AMPs are instrumental in suppressing pathogenic bacterial growth, preventing the transplantation and invasion of pathogenic microorganisms and creating a conducive environment for normal flora to thrive.…”