The effect of nerve cells on the intestinal barrier function and the influence of human milk oligosaccharides (hMOs) on the intestinal neuro-epithelial crosstalk

Abstract

The intestinal epithelium is an important gatekeeper of the human body by forming a barrier for the luminal content of the intestine. The barrier function is regulated by a complex crosstalk between different cell types, including cells from the enteric nervous system (ENS). ENS is considered to influence gastrointestinal processes and functions, but its direct effect on epithelial barrier function remains to be confirmed. To investigate the effect of nerve cells on the gut barrier function, an in vitro co-culture system was established in which T84 intestinal epithelial cells and SH-SY5Y nerve cells were seeded in ratios of 29:1 and 14:1. When the epithelial barrier was disrupted with the calcium ionophores A23187, we found that nerve cells exert a protective effect on A23187-induced disruption and that this protective effect is nerve cell concentration-dependent. This was demonstrated by rescuing effects on transepithelial electrical resistance (TEER) and upregulation of tight junction (TJ) protein expression. Furthermore, we studied whether similar rescuing effects could be achieved with the human milk oligosaccharides (hMOs) 2′-fucosyllactose (2′-FL) and 3-fucosyllactose (3-FL). Our results illustrate that in the presence of nerve cells 2′-FL and 3-FL do not have any additional rescuing effects, but that these hMOs can substitute the rescuing effects of nerve cells in the absence of nerve cells. Meanwhile, 2′-FL and 3-FL show different regulation effects on TJ expression. These findings provide valuable insights into potential therapeutic strategies for maintaining intestinal barrier integrity.