The gut microbiota-immune-brain axis in post-traumatic stress disorder: mechanistic integration and translational prospects.

Post-traumatic stress disorder (PTSD) is a complex mental disorder triggered by severe traumatic events. Its pathophysiology involves not only abnormalities in fear memory circuits and neuroendocrine imbalances but also immune dysregulation and alterations in gut homeostasis. In recent years, the gut microbiota, as a crucial regulatory factor connecting the periphery and the central nervous system, has garnered widespread attention for its potential role in the development and progression of PTSD, offering a new integrative perspective for understanding this disorder. This article focuses on the "gut microbiota-immune-brain axis" framework, reviewing evidence related to changes in the composition and function of the gut microbiota in PTSD. It summarizes how these changes may influence neuroplasticity abnormalities and PTSD-related behavioral phenotypes through mechanisms involving microbial metabolite production, modulation of intestinal barrier integrity, immuno-inflammatory responses, regulation of neuroendocrine homeostasis, and blood-brain barrier dysfunction. However, these mechanistic pathways remain incompletely validated in human studies. Existing research suggests that this axis holds significant value in explaining the multisystem pathological features of PTSD. Nevertheless, challenges persist, including ambiguous causal relationships in microbiota-host interactions, limited direct clinical evidence, and insufficient translational research. Current evidence primarily stems from observational studies, preclinical models, and preliminary intervention studies. The explanatory power varies across these evidence levels: population studies primarily establish correlations, animal models facilitate mechanistic validation, metagenomic and metabolic analyses yield functional insights, while clinical intervention data remain exploratory. This article aims to elucidate the key molecular and systemic mechanisms underlying this axis in PTSD and to evaluate the potential translational value and practical limitations of microbial intervention and immune modulation strategies.