Impact of Enteric Nervous Cells on Irritable Bowel Syndrome: Potential Treatment Options

Abstract

Irritable bowel syndrome (IBS) is a condition that significantly impacts the lifestyle, health, and habits of numerous individuals worldwide. Its diagnosis and classification are based on the Rome criteria, updated periodically to reflect new research findings in this field. IBS can be classified into different types based on symptoms, each with distinct treatment approaches and some differences in their pathophysiology. The exact pathological background of IBS remains unclear, with many aspects still unknown. Recent research developments suggest that disorders in the brain-gut-microbiota axis are key contributors to the symptoms and severity of IBS. The central nervous system (CNS) interacts bidirectionally with intestinal processes within the lumen and the intestinal wall, with the autonomic nervous system, particularly the vagus nerve, playing an important role. However, the enteric nervous system (ENS) is also crucial in the pathophysiological pathway of IBS. The apeline-corticotropin-releasing factor (CRF)-toll-like receptor 4 (TLR4) signaling route via enteric glia and serotonin production in enteroendocrine cells at the enteric barrier are among the most well-understood new findings that affect IBS through the ENS. Additionally, the microbiota regulates neuronal signals, modifying enteric function by altering the number of enteric bacteria and other mechanisms. Given the limited therapeutic options currently available, it is essential to identify new treatment targets, with the brain-gut axis, particularly the enteric nervous system, being a promising focus. This study aims to delineate the molecular mechanisms that induce IBS and to suggest potential targets for future research and treatment of this potentially debilitating disease.

Keywords: central nervous system; enteric nervous cells; enteric nervous system; gut microbiota; irritable bowel syndrome; management; mechanisms; signaling.

Figure 1

Impact of enteric nervous cells on irritable bowel syndrome (IBS) and the role of microbiota. The diagram illustrates the intricate interactions between enteric nervous cells, the gut microbiota, and immune responses, and their impact on irritable bowel syndrome (IBS). The bidirectional relationship between the gut microbiota and the enteric nervous system (ENS) is highlighted, emphasizing how microbial metabolites, immune activation, and neuroimmune interactions contribute to the pathophysiology of IBS. Diet influences the gut microbiome, leading to the production of short-chain fatty acids (SCFAs) and other microbial metabolites, which are crucial for maintaining gut health and modulating the ENS. Alterations in the microbiota can increase intestinal permeability, allowing lipopolysaccharides (LPSs) to cross the epithelial barrier. LPSs activate immune cells such as macrophages, dendritic cells (DCs), T cells, and mast cells, resulting in the release of proinflammatory cytokines. Enteric nervous cells play significant roles in gut physiology and pathology. Serotonin (5-HT), which is released by the enteroendocrine cells, modulates gut motility and sensitivity. Corticotropin-releasing factor (CRF) increases the intestinal permeability and promotes the inflammatory responses through the toll-like receptor 4 (TLR4)-mediated signaling. Brain-derived neurotrophic factor (BDNF) supports neuroplasticity, modulates sensory neurons, and helps maintain the intestinal barrier. Apelin helps mitigate barrier function disruption, preventing bacterial translocation and TLR activation. TLR4 recognizes LPSs, initiating innate immune responses and increasing the production of proinflammatory cytokines. Created with BioRender.com (accessed on 26 August 2024).