Guardians of the gut: influence of the enteric nervous system on the intestinal epithelial barrier

Abstract

The intestinal mucosal surface forms one of the largest areas of the body, which is in direct contact with the environment. Co-ordinated sensory functions of immune, epithelial, and neuronal cells ensure the timely detection of noxious queues and potential pathogens and elicit proportional responses to mitigate the threats and maintain homeostasis. Such tuning and maintenance of the epithelial barrier is constantly ongoing during homeostasis and its derangement can become a gateway for systemic consequences. Although efforts in understanding the gatekeeping functions of immune cells have led the way, increasing number of studies point to a crucial role of the enteric nervous system in fine-tuning and maintaining this delicate homeostasis. The identification of immune regulatory functions of enteric neuropeptides and glial-derived factors is still in its infancy, but has already yielded several intriguing insights into their important contribution to the tight control of the mucosal barrier. In this review, we will first introduce the reader to the current understanding of the architecture of the enteric nervous system and the epithelial barrier. Next, we discuss the key discoveries and cellular pathways and mediators that have emerged as links between the enteric nervous, immune, and epithelial systems and how their coordinated actions defend against intestinal infectious and inflammatory diseases. Through this review, the readers will gain a sound understanding of the current neuro-immune-epithelial mechanisms ensuring intestinal barrier integrity and maintenance of intestinal homeostasis.

Optogenetics-integrated gut organ culture system connects enteric neurons dynamics and gut homeostasis

“…Emerging evidence suggest that the ENS coordinates epithelial integrity and barrier protection 12,13,26 . To determine whether on-chip activation of distinct neuronal subtypes and activation patterns affects epithelial tight junction (TJ) integrity, homozygote ChAT-ChR2 and heterozygote Tac1-ChR2 colons were optogenetically activated at 2/10Hz.…”

The Imperative for Innovative Enteric Nervous System–Intestinal Organoid Co-Culture Models: Transforming GI Disease Modeling and Treatment

“…The influence of the ENS on the intestinal epithelium and the intestinal immune system and vice versa has been previously investigated in vivo and ex vivo [8,[177][178][179]. Co-culture of HIOs and differentiated ENS from human ESCs resulted in increased epithelial proliferation [80].…”

Enteric Nervous System Alterations in Inflammatory Bowel Disease: Perspectives and Implications

“…EGCs provide structural and metabolic support for enteric neurons through a close association with neuronal cells and also express receptors for neurotransmitters such as serotonin, gamma-aminobutyric acid (GABA), and glutamate, allowing them to respond to neuronal activity and regulate synaptic transmission [37,54]. Additionally, EGCs also contribute to the maintenance of the intestinal epithelial barrier, which is compromised in IBD [55]. They regulate the expression of tight junction proteins and mucins, which are essential for epithelial integrity and protection against luminal pathogens [56].…”