Sepsis-associated gastrointestinal dysfunction: neuroimmune mechanisms, gut-brain axis disruption, and therapeutic potential of vagus nerve-targeted neuromodulation.

Sepsis-associated gastrointestinal dysfunction (SAGD) is a frequent complication in critically ill patients, marked by impaired motility, feeding intolerance, and disruption of the intestinal barrier, and is linked to poor clinical outcomes. Growing evidence indicates that SAGD arises from the interaction between systemic inflammation and neuroimmune dysregulation. Pro-inflammatory cytokines such as tumor necrosis factor, interleukin-1β, and interleukin-6 promote epithelial injury, disturb tight junction integrity, and impair neuromuscular function, while microcirculatory disturbances further aggravate tissue hypoxia and barrier breakdown. At the same time, alterations in the gut-brain axis and autonomic imbalance compromise gastrointestinal motility and disrupt the cholinergic anti-inflammatory pathway, suggesting that SAGD represents a coordinated inflammatory-barrier-neuroimmune disorder. Current management remains mainly supportive and does not target these underlying processes. As a central element of the gut-brain axis, the vagus nerve plays a key role in regulating both immune responses and gastrointestinal function. Neuromodulation approaches aimed at vagal pathways-especially transcutaneous auricular vagus nerve stimulation (taVNS)-have therefore attracted attention as non-invasive strategies to influence inflammation and autonomic balance. Although direct clinical evidence in SAGD is still limited, the biological rationale supports further exploration.