Intestinal barrier function in the naked mole-rat: an emergent model for gastrointestinal insights

Abstract

The intestinal barrier plays a crucial role in homeostasis, both by facilitating absorption of nutrients and providing a tight shield to prevent the invasion by either pathogen or commensal microorganisms. Intestinal barrier malfunction is associated with systemic inflammation, oxidative stress, and decreased insulin sensitivity, which may lead to the dysregulation of other tissues such as the liver, fat, skeletal muscle, and brain. Hence, a deeper understanding of physiological aspects related to an enhanced barrier function is of great clinical relevance. The naked mole-rat (Heterocephalus glaber) has many unusual biological features, including impaired colonic neuron sensitivity to acid and bradykinin, and resistance to chemically induced intestinal damage. However, insight into their intestinal barrier physiology is scarce. Here, we observed notable differences in intestinal tissue structure between naked mole-rats and mice, especially in the ileum. This was characterised by thicker muscularis and submucosa layers, longer villi and larger crypts. In measuring gut permeability, naked mole-rats showed reduced permeability compared to mice, especially in the small intestine (ileum). Furthermore, intestinal anion secretion induced by serotonin, bradykinin, histamine and capsaicin was significantly impaired in naked mole-rats compared to mice, despite the expression of receptors for all these agonists. Collectively, these findings indicate that naked mole-rats possess a robust gastrointestinal barrier, that is hard to penetrate and is resistant to environmental and endogenous irritants. Naked mole-rats may therefore provide valuable insights into the physiology of the intestinal barrier related to different pathological conditions and set the stage for the development of innovative and effective therapies.