Abstract
BACKGROUND: The enteric nervous system (ENS), often referred to as the "second brain", plays a vital role in regulating gastrointestinal (GI) functions such as motility, secretion, and immune responses. Located within the walls of the gastrointestinal tract, the ENS is involved in several GI disorders, including functional gastrointestinal disorders like irritable bowel syndrome (IBS), motility disorders such as gastroparesis, and conditions like inflammatory bowel diseases (IBD) and congenital aganglionosis. Understanding the mechanisms and therapeutic potential of the ENS is crucial for advancing treatment options for these conditions. AIM: To review the therapeutic targeting of the ENS in treating gastrointestinal disorders, with a focus on the mechanisms of action, current therapies, and emerging treatment strategies. METHODS: This review adhered to Preferred Reporting Items for Systematic Reviews and Meta-analyses 2009 guidelines and included a comprehensive literature search across PubMed, Scopus, and Google Scholar from 2010 onwards. Studies were selected based on their exploration of the structure, function, and pathology of the ENS in relation to gastrointestinal diseases, particularly motility disorders and inflammation. Articles were evaluated for therapeutic strategies, including pharmacological, surgical, and gene-based interventions. RESULTS: The ENS is found to regulate essential functions like peristalsis, secretion, and immune responses, and its dysfunction leads to a variety of gastrointestinal diseases. Recent studies highlight several promising therapies targeting ENS neurotransmitters, including serotonin receptor modulators, prokinetic agents, and neuroprotective strategies aimed at enteric glial cells. These approaches have shown promise in treating conditions like IBS, gastroparesis, and IBD. Additionally, bioelectronic therapies and stem cell-based treatments are emerging as potential therapies for ENS regeneration. CONCLUSION: Targeting the ENS offers novel therapeutic avenues for treating gastrointestinal disorders. Advances in pharmacological treatments, gene therapy, and neuromodulation techniques show great promise in restoring ENS function and improving clinical outcomes. While current research remains in early stages, future studies focusing on personalized medicine and the gut-brain axis could lead to more effective treatments for complex gastrointestinal diseases.