Figure 1. The gut functions as a dynamic barrier to the environment with signal integration properties.

The gut functions as a chemical and physical barrier to the environment and serves as an integration site to respond to diverse intrinsic as well as extrinsic stimuli. These stimuli display a wide range of metabolites, age‐related changes, microbiota as well as inflammation‐associated processes. The resulting functional consequences include adaption in stem cell and proliferation, immune responses, reinforcement of the barrier function, cellular senescence as well as stem cell exhaustion. Functional consequences constantly affect the epithelial homeostasis and subsequently the barrier function of the intestine, eventually leading to epithelial barrier defects.