Distinguishing the causative, correlative and bidirectional roles of the gut microbiota in mental health

The gut microbiota, the dynamic orchestrator of physiological and neuroimmune processes, influences mental health via the bidirectional microbiota–gut–brain axis. Although distinct microbial signatures are linked with psychiatric disorders such as depression, anxiety, post-traumatic stress disorder and schizophrenia, whether this relationship is causative, correlative or represents a complex interplay remains unresolved. This Review examines this trichotomy, highlighting key mechanistic pathways including microbial metabolites, immune modulation and neural signaling, alongside challenges in disentangling causation from correlation. Clarifying this distinction elevates the gut microbiota from a curiosity to a cornerstone of personalized medicine. Furthermore, emphasis is placed on advancing methodological frameworks, fostering interdisciplinary collaboration and addressing research disparities that bias insights toward specific populations. Clearer understanding of the microbiota’s role in mental health could yield new therapies and predictive biomarkers, ultimately charting paths toward more equitable and evidence-based approaches. This work outlines the transformative potential of clarifying the microbiota–gut–brain axis in addressing global mental health burden.