Microenvironmental Metabolites in the Intestine: Messengers between Health and Disease

The intestinal mucosa is a highly absorptive organ and simultaneously constitutes the physical barrier between the host and a complex outer ecosystem. Intestinal epithelial cells (IECs) represent a special node that receives signals from the host and the environment and translates them into corresponding responses. Specific molecular communication systems such as metabolites are known to transmit information across the intestinal boundary. The gut microbiota or food-derived metabolites are extrinsic factors that influence the homeostasis of the intestinal epithelium, while mitochondrial and host-derived cellular metabolites determine the identity, fitness, and regenerative capacity of IECs. Little is known, however, about the role of intrinsic and extrinsic metabolites of IECs in the initiation and progression of pathological processes such as inflammatory bowel disease and colorectal cancer as well as about their impact on intestinal immunity. In this review, we will highlight the most recent contributions on the modulatory effects of intestinal metabolites in gut pathophysiology, with a particular focus on metabolites in promoting intestinal inflammation or colorectal tumorigenesis. In addition, we will provide a perspective on the role of newly identified oncometabolites from the commensal and opportunistic microbiota in shaping response and resistance to antitumor therapy.

Automated summary

The intestinal mucosa is an absorptive organ that acts as a barrier between the host and the external environment. Intestinal epithelial cells (IECs) receive signals from the host and the environment and respond accordingly. Metabolites, such as those from the gut microbiota or food, transmit information across the intestinal barrier. Little is known about the role of intrinsic and extrinsic metabolites of IECs in diseases like inflammatory bowel disease and colorectal cancer, as well as their impact on intestinal immunity. This review focuses on the recent research on the effects of intestinal metabolites in gut pathophysiology, particularly in promoting intestinal inflammation and colorectal tumorigenesis. It also discusses the role of newly identified oncometabolites from the commensal and opportunistic microbiota in shaping response and resistance to antitumor therapy.