Chemotherapy-induced mucosal barrier dysfunction: an updated review on the role of intestinal tight junctions

Gut toxicity, or mucositis, is a major dose-limiting side effect of chemotherapy that until recently received very little attention. Despite significant research, the mechanisms that underpin chemotherapy-induced gut toxicity (CIGT) remain unclear. Recently however, there has been renewed interest in the role tight junctions play in the pathogenesis of CIGT and associated diarrhea. Thus, this review will cover the role of tight junctions in maintaining gastrointestinal homeostasis and touch on recently proposed mechanisms of how tight junctions may contribute to the development of chemotherapy-induced diarrhea.

There is a wealth of anecdotal evidence regarding the role of tight junctions in the pathogenesis of gut toxicity. However, few studies have quantified or assessed the molecular changes in tight junctions in response to chemotherapy. This review will highlight the major findings of these studies and discuss the potential mechanisms by which tight junction disruption and mucosal barrier dysfunction may contribute to diarrhea.

The significant clinical and economic impact associated with CIGT and diarrhea has only recently been appreciated. This has prompted significant research efforts in an attempt to reveal the pathophysiology of this debilitating complication. Renewed interest has been shown regarding the role of tight junctions in not only maintaining gastrointestinal health, but also contributing to mucosal barrier injury and diarrhea development. More detailed research into the effect chemotherapy has on the molecular characteristics of tight junctions will lead to a better understanding of the pathophysiology of CIGT and may uncover the therapeutic potential of tight junctions in treating diarrhea.