Enteric glial cells as regulators of the gut-brain axis: hormonal signaling, stress responses and progenitor potential

Enteric glial cells (EGCs) are increasingly recognized as key regulators of the gut-brain axis, extending far beyond their traditional role as structural support cells within the enteric nervous system. Growing evidence demonstrates that EGCs integrate neuronal, immune, epithelial, and microbial signals to maintain intestinal homeostasis and coordinate adaptive responses to physiological and pathological stimuli. This review summarizes current knowledge on enteric glial heterogeneity, stress responsiveness, hormonal regulation, and their emerging capacity for regenerative plasticity. While inflammatory and oxidative stress responses of EGCs are increasingly well characterized, their regulation by endocrine signaling remains poorly understood despite accumulating evidence for sex-dependent differences and hormone receptor expression. Furthermore, recent studies suggest that EGCs retain facultative progenitor properties and may contribute to tissue repair and neuronal regeneration under specific conditions. By integrating these largely independent research areas, we propose a conceptual framework in which enteric glia function as central signal integrators linking stress, hormonal signaling, and regenerative responses within the gut-brain axis. A better understanding of these mechanisms may identify enteric glia as promising therapeutic targets for gastrointestinal and neurodegenerative diseases.