Cellular Stress Responses and Gut Microbiota in Inflammatory Bowel Disease.

Siyan “Stewart” Cao

doi:10.1155/2018/7192646

Abstract

Progresses in the past two decades have greatly expanded our understanding of inflammatory bowel disease (IBD), an incurable disease with multifaceted and challenging clinical manifestations. The pathogenesis of IBD involves multiple processes on the cellular level, which include the stress response signaling such as endoplasmic reticulum (ER) stress, oxidative stress, and hypoxia. Under physiological conditions, the stress responses play key roles in cell survival, mucosal barrier integrity, and immunomodulation. However, they can also cause energy depletion, trigger cell death and tissue injury, promote inflammatory response, and drive the progression of clinical disease. In recent years, gut microflora has emerged as an essential pathogenic factor and therapeutic target for IBD. Altered compositional and metabolic profiles of gut microbiota, termed dysbiosis, are associated with IBD. Recent studies, although limited, have shed light on how ER stress, oxidative stress, and hypoxic stress interact with gut microorganisms, a potential source of stress in the microenvironment of gastrointestinal tract. Our knowledge of cellular stress responses in intestinal homeostasis as well as their cross-talks with gut microbiome will further our understanding of the pathogenesis of inflammatory bowel disease and probably open avenues for new therapies.

Highlights

Inflammatory bowel disease (IBD) affects more than 3.1 million people in the United States and 2.5 million in Europe and is increasing in incidence worldwide especially in regions such as Eastern and South Asia [1, 2]
IBD including Crohn’s disease (CD) and ulcerative colitis (UC) are characterized by chronic intestinal inflammation as well as extraintestinal manifestations, which are likely triggered by a combination of genetic predispositions and environmental factors such as diet, infection, and medication use [3]
Through complex interactions with the stress pathways in the host cells, these microorganisms may contribute to the pathogenesis of IBD by inducing cell death and differentiation, epithelial barrier breakdown, and inflammatory response

Summary

Introduction

Inflammatory bowel disease (IBD) affects more than 3.1 million people in the United States and 2.5 million in Europe and is increasing in incidence worldwide especially in regions such as Eastern and South Asia [1, 2]. The complex pathophysiology of IBD involves multiple cell populations in the gastrointestinal tract and numerous signaling pathways from energy homeostasis to innate immune response. Recent evidence suggests that stress signaling plays a key role in mucosal homeostasis in the gut. Through complex interactions with the stress pathways in the host cells, these microorganisms may contribute to the pathogenesis of IBD by inducing cell death and differentiation, epithelial barrier breakdown, and inflammatory response. Targeting cellular stress signaling and the gut microbiota have been proposed as new therapies for UC and CD. The understanding of both sides and the bridge between the two will likely spur the progresses in this arena

Cellular Stress Signaling in Gastrointestinal Tract

Cellular Stress Responses Interact with Microbiome in Gastrointestinal Tract

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