The emerging roles of autophagy in intestinal epithelial cells and its links to inflammatory bowel disease

Landmark genome-wide association studies (GWAS) identified that mutations in autop-hagy genes correlated with inflammatory bowel disease (IBD), a heterogenous disease characterised by prolonged inflammation of the gastrointestinal tract, that can reduce a person's quality of life. Autophagy, the delivery of intracellular components to the lyso-some for degradation, is a critical cellular housekeeping process that removes damaged proteins and turns over organelles, recycling their amino acids and other constituents to supply cells with energy and necessary building blocks. This occurs under both basal and challenging conditions such as nutrient deprivation. An understanding of the relation-ship between autophagy, intestinal health and IBD aetiology has improved over time, with autophagy having a verified role in the intestinal epithelium and immune cells. Here, we discuss research that has led to an understanding that autophagy genes, including ATG16L, ATG5, ATG7, IRGM, and Class III PI3K complex members, contribute to innate immune defence in intestinal epithelial cells (IECs) via selective autophagy of bacteria (xenophagy), how autophagy contributes to the regulation of the intestinal barrier via cell junctional proteins, and the critical role of autophagy genes in intestinal epithelial secre-tory subpopulations, namely Paneth and goblet cells. We also discuss how intestinal stem cells can utilise autophagy. Importantly, mouse studies have provided evidence that autophagy deregulation has serious physiological consequences including IEC death and intestinal inflammation. Thus, autophagy is now established as a key regulator of intes-tinal homeostasis. Further research into how its cytoprotective mechanisms can prevent intestinal inflammation may provide insights into the effective management of IBD.

Automated summary

Landmark GWAS studies have found a correlation between mutations in autophagy genes and inflammatory bowel disease (IBD), which is characterized by prolonged inflammation of the gastrointestinal tract and can greatly affect a person's quality of life. Autophagy is a critical cellular process that helps maintain intestinal health and plays a role in innate immune defense. Further research into the mechanisms of autophagy and its role in preventing intestinal inflammation may have implications for the management of IBD.