Mast cells in digestive diseases: New insights to keep them under control

The gut mucosa serves as an essential interface between the internal and external environment, providing a continuous barrier against possible harmful luminal content. The regulation of this protective function is controlled by immune-mediated and non-immune mechanisms, wherein mast cells (MCs) play a key role. These versatile immune cells are strategically located in the lining of the gastrointestinal (GI) tract, where they help maintain the integrity of the intestinal barrier, regulate blood flow, control the entry of immune cells into tissues, and participate in various physiological processes, such as wound healing and intestinal peristalsis. However, excessive MC activation may disturb the gut balance, which could cause a "leaky gut", where increased permeability of the intestinal lining allows substances to pass into the bloodstream, causing various health problems. Studies have confirmed an increased presence of MCs in the intestinal lining of individuals with compromised barriers, as seen in conditions like gastrointestinal diseases (GIDs). Hence, precise regulation of MC activity is essential for maintaining intestinal health and limiting disease progression. In this review, we aim to offer a comprehensive and current overview of the role of MCs in GIDs by delving into their origins, functions, and interactions in the GI environment. We explore the "leaky gut" concept, examining how MCs influence the intestinal barrier and its association with GIDs. Additionally, we describe the latest advancements in MC research, including targeted therapies and potential future directions.