The gastrointestinal tract is the only organ with an intrinsic nervous system, the enteric nervous system (ENS), composed by two ganglionated plexi, the myenteric and the submucosal plexus. The ENS encompass 1X108/5X108 neurons subdivided into different classes that are integrated into other cell types: glial, muscular, epithelial, vascular, enteroendocrine, immune cells, interstitial cells of Cajal, and microbiota. This network is finely regulated to coordinate sensory and motor functions of the gut, as well as immune responses and microvascular circulation. Any changes in the cellular components of this network, or alterations in their interaction, can trigger both intestinal and extra-intestinal pathologies.

While the development of the ENS and related diseases has been largely studied, limited information is available concerning ENS maintenance. This issue certainly deserves to be further explored, taking into account all of the stressors to which the gastrointestinal tract is constantly subjected (i.e. mechanical stress, chemical insults from luminal contents, noxae interaction) in association with all the cellular components that have a role to preserve the correct gastrointestinal homeostasis.

This Special Issue encourages authors to submit review articles as well as basic and translational original research papers on the newly acquired knowledge to shed light on this challenging topic.

Potential topics include but are not limited to the following:

• From cellular models to 3D cultures: new insights on oxidative stress model systems to test gastrointestinal neuroprotective drugs
• Immune response, interactions between the immune system and ENS, oxidative stress and enteric neuronal cells: new insights on neurodegenerative diseases affecting the gut and therapeutic options
• The role of serotonin in gastrointestinal neuron survival and neurogenesis
• Neuronal stem cells and gastrointestinal diseases
• The role of aging on the microbiota and neuroanatomical changes in the ENS
• The role of diet and lifestyle on the microbiota in the remodelling of the ENS, and the importance of prebiotics, probiotics, and the impact of diet in the delicate balance between biosis and dysbiosis
• Epithelial and vascular barrier alterations and the impact on ENS, and the importance of epithelial and endothelial cell maintenance
• Ageing as a risk factor for a permeable epithelial barrier and the new molecular predictors of gastrointestinal permeability, from diagnosis to new strategies to restore the epithelial barrier and their effects on the ENS
• Application of tissue engineering and regenerative medicine techniques to restore the architecture and functions of the gastrointestinal tract and their limitations connected to age, health status and diet