The microbiome and PTSD: a scoping review across preclinical and clinical studies.

Abstract

Background: Posttraumatic Stress Disorder (PTSD) is a psychiatric condition that substantially impairs quality of life and global health. Emerging evidence implicates that the human microbiome contributes to PTSD pathophysiology via gut-brain-immune interactions, although the underlying mechanisms and therapeutic implications remain unclear.

Objective: This review aimed to systematically map the evidence linking microbiome alterations to PTSD, with a focus on mechanistic pathways, therapeutic potential, and research gaps.

Methods: This scoping review was conducted in Medline, Embase, and PsychINFO from inception to 18-03-2025. Eligible studies included human participants with PTSD and preclinical rodent models employing validated PTSD paradigms. Outcomes of interest included microbiome diversity and composition, gut-brain axis biomarkers, and effects of microbiome-targeted interventions.

Results: Fifty studies were included, comprising 20 human, 29 preclinical and one cross-species study. Human observational studies frequently observed reduced overall microbial diversity, along with a loss of short-chain fatty acid (SCFA)-producing bacteria, such as Ruminococcaceae and Lachnospiraceae, and an increased abundance of Veillonella, Odoribacter, and Catenibacterium linked to gut permeability and inflammation. Human intervention studies testing probiotics, prebiotics, fermented soy, and dietary fibre showed preliminary evidence for symptom and related metabolic and inflammatory marker improvements; however, microbiome effects were inconsistent. Preclinical models revealed stress-induced reductions in Bifidobacteria, Verrucomicrobia, and Parabacteroides, and increases in Coprobacillus and Anaeroplasma. Functional consequences included impaired barrier integrity, altered SCFA levels, and heightened immune activation. Preclinical interventions, particularly Mycobacterium vaccae, as well as probiotics, synbiotics, acetate, and MDMA, mitigated microbial alterations, reduced anxiety-like behaviours, and modulated neuroimmune pathways.

Conclusion: Current evidence supports an association between PTSD and microbiome alterations, with convergent human and preclinical findings. However, human research remains limited by small, cross-sectional designs, which preclude causal inferences. Rigorous longitudinal and interventional studies are required to establish causality and assess microbiome-targeted therapies as adjuncts in PTSD treatment.