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

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Original abstract

<h4>Background</h4>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.<h4>Objective</h4>This review aimed to systematically map the evidence linking microbiome alterations to PTSD, with a focus on mechanistic pathways, therapeutic potential, and research gaps.<h4>Methods</h4>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.<h4>Results</h4>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 <i>Veillonella</i>, <i>Odoribacter</i>, and <i>Catenibacterium</i> 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 <i>Bifidobacteria</i>, Verrucomicrobia, and <i>Parabacteroides</i>, and increases in <i>Coprobacillus</i> and <i>Anaeroplasma</i>. Functional consequences included impaired barrier integrity, altered SCFA levels, and heightened immune activation. Preclinical interventions, particularly <i>Mycobacterium vaccae</i>, as well as probiotics, synbiotics, acetate, and MDMA, mitigated microbial alterations, reduced anxiety-like behaviours, and modulated neuroimmune pathways.<h4>Conclusion</h4>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.

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