Gut commensal bacteria, Paneth cells and their relations to radiation enteropathy

Abstract

In steady state, the intestinal epithelium forms an important part of the gut barrier to defend against luminal bacterial attack. However, the intestinal epithelium is compromised by ionizing irradiation due to its inherent self-renewing capacity. In this process, small intestinal bacterial overgrowth is a critical event that reciprocally alters the immune milieu. In other words, intestinal bacterial dysbiosis induces inflammation in response to intestinal injuries, thus influencing the repair process of irradiated lesions. In fact, it is accepted that commensal bacteria can generally enhance the host radiation sensitivity. To address the determination of radiation sensitivity, we hypothesize that Paneth cells press a critical “button” because these cells are central to intestinal health and disease by using their peptides, which are responsible for controlling stem cell development in the small intestine and luminal bacterial diversity. Herein, the most important question is whether Paneth cells alter their secretion profiles in the situation of ionizing irradiation. On this basis, the tolerance of Paneth cells to ionizing radiation and related mechanisms by which radiation affects Paneth cell survival and death will be discussed in this review. We hope that the relevant results will be helpful in developing new approaches against radiation enteropathy.

Keywords: Gut commensal bacteria; Paneth cell; Radiation enteropathy; Epithelial homeostasis; Gut immunity; Intestinal defense

Core tip: In healthy individuals, Paneth cells restrict the overgrowth of commensal bacteria in the gut while killing luminal pathogenic bacteria by secreting antimicrobial peptides. Such a property protects crypt intestinal stem cells against bacterial infection, thus ensuring epithelial homeostasis in steady state. Among the active pool of intestinal stem cells, apoptosis commonly occurs as a result of ionizing irradiation. Nevertheless, the intestinal epithelium will recover its integrity after sublethal irradiation. On this basis, the mechanism by which Paneth cells provide growth signals for intestinal stem cells to facilitate epithelial regeneration is easy to understand, whereas the automatic recovery of irradiated intestine from sublethal irradiation is perplexing. Being challenged with luminal bacteria, the degranulation of Paneth cells can be stimulated in a cholinergic- or inflammatory-substance-dependent manner. Then, Paneth cells can perform an antibacterial function that influences the inflammatory milieu in irradiated intestine. Therefore, radiation-induced intestinal bacterial dysbiosis can be managed.