Oxygen in the regulation of intestinal epithelial transport

The transport of fluid, nutrients and electrolytes to and from the intestinal lumen is a primary function of epithelial cells. Normally, the intestine absorbs approximately 9 l of fluid and 1 kg of nutrients daily, driven by epithelial transport processes that consume large amounts of cellular energy and O2. The epithelium exists at the interface of the richly vascularised mucosa, and the anoxic luminal environment and this steep O2 gradient play a key role in determining the expression pattern of proteins involved in fluid, nutrient and electrolyte transport. However, the dynamic nature of the splanchnic circulation necessitates that the epithelium can evoke co-ordinated responses to fluctuations in O2 availability, which occur either as a part of the normal digestive process or as a consequence of several pathophysiological conditions. While it is known that hypoxia-responsive signals, such as reactive oxygen species, AMP-activated kinase, hypoxia-inducible factors, and prolyl hydroxylases are all important in regulating epithelial responses to altered O2 supply, our understanding of the molecular mechanisms involved is still limited. Here, we aim to review the current literature regarding the role that O2 plays in regulating intestinal transport processes and to highlight areas of research that still need to be addressed.