Autophagy and Digestive Disorders: Advances in Understanding and Therapeutic Approaches

Abstract

The gastrointestinal (GI) tract is a series of hollow organs that is responsible for the digestion and absorption of ingested foods and the excretion of waste. Any changes in the GI tract can lead to GI disorders. GI disorders are highly prevalent in the population and account for substantial morbidity, mortality, and healthcare utilization. GI disorders can be functional, or organic with structural changes. Functional GI disorders include functional dyspepsia and irritable bowel syndrome. Organic GI disorders include inflammation of the GI tract due to chronic infection, drugs, trauma, and other causes. Recent studies have highlighted a new explanatory mechanism for GI disorders. It has been suggested that autophagy, an intracellular homeostatic mechanism, also plays an important role in the pathogenesis of GI disorders. Autophagy has three primary forms: macroautophagy, microautophagy, and chaperone-mediated autophagy. It may affect intestinal homeostasis, host defense against intestinal pathogens, regulation of the gut microbiota, and innate and adaptive immunity. Drugs targeting autophagy could, therefore, have therapeutic potential for treating GI disorders. In this review, we provide an overview of current understanding regarding the evidence for autophagy in GI diseases and updates on potential treatments, including drugs and complementary and alternative medicines.

Resveratrol alleviates enterotoxigenicEscherichia coliK88-induced damage by regulating SIRT-1 signaling in intestinal porcine epithelial cells

“…The dysfunctional autophagy mechanism leads to intestinal barrier injury and chronic intestinal inflammation in humans and animals. 68,69…”

“…The dysfunctional autophagy mechanism leads to intestinal barrier injury and chronic intestinal inflammation in humans and animals. 68,69 The protective effects of resveratrol treatment during different kinds of disorders and diseases have been widely reported to associate with its regulatory role on autophagy and mitophagy, involved in several cell signaling molecules like p62, AMPK, SIRT-1 and other targets. [70][71][72][73][74] However, few research studies focus on resveratrol's regulatory effect on the autophagy pathway to mediate intestinal physiological function 23,75 and the underlying mechanism remains unclear.…”

The role of sphingosine-1-phosphate in autophagy and related disorders

“…Autophagy disorders have been implicated in the pathogenesis of various digestive diseases, including pancreatitis, IBD, colon cancer, and liver diseases [ 165 ]. S1P receptors are widely expressed in the digestive system and play different roles in autophagy regulation.…”

Alternative autophagy: mechanisms and roles in different diseases

“…Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is characterized with abnormal inflammatory and immune responses in the intestine [73,74]. Genome-wide associated investigations indicated that numerous canonical autophagy genes have involve in IBD [75,76].…”