Reactive Oxygen Species in Modulating Intestinal Stem Cell Dynamics and Function

Abstract

Frequent exposure to mechanistic damages, pathological ingression, and chronic inflammation leads to recurrent cell death in the gut epithelium. Intestinal stem cells (ISCs) that reside in crypt-specific niches have an unprecedented role in gut epithelium renewal. ISC also facilitates the formation of mature intestinal epithelial cells (IECs) through regular differentiation and renewal in short turnover cycles. Interestingly, oxidative stress (OS) prevalent in the gut has a dominant role in the regulation of ISC proliferation and development. However, it is unclear, which axis OS controls the cellular signaling and underlying molecular mechanism to drive ISC turnover and regeneration cycle. Therefore, this review provides a comprehensive overview of the present understanding of OS generation in the gut, relatively directing the ISC development and regeneration under a conditional cellular environment. Additionally, the focus has been drawn on intestinal nutritional state and its related alteration on OS and its effect on ISCs. Moreover, recent findings and new approaches are emphasized herewith to enhance the present understanding of the mechanisms that direct universal ISC characteristics. Intestinal stem cells (ISC) form the basis of all repair mechanisms that help in the proliferation of the gut through their constant renewal and replacement. This activity is closely regulated in the ISC niche and is modulated by several extrinsic as well as intrinsic factors. Reactive Oxygen Species (ROS) form one of the major factors that influence ISC formation. The levels of ROS in the gut influence stem cell renewal ROS itself however is further influenced by several other factors such as the microbiota concerning the gut and immune cells which in turn also influence one another by various cross-talk mechanisms. Diet also forms an important part of this crosstalk. It also regulates the levels of ROS in the gut and helps in the proliferation of the ISC cells and their overall turnover rate.

Keywords: Gut Microbiome; Intestinal Stem Cell (ISC); Nutrition; Oxidative Stress (OS); ROS.