Inflammatory biomarkers and oral microbiome alterations in depression and anxiety disorders: a systematic review

Depression and anxiety are increasingly linked to systemic inflammation and microbiome alterations, yet the role of the oral microbiome remains poorly characterised. This systematic review synthesises recent human evidence examining associations between depression or anxiety and (1) peripheral or salivary inflammatory biomarkers and (2) oral microbiome alterations.

Following PRISMA 2020 guidance, PubMed, Web of Science, and PsycINFO were searched for studies published between 2016 and 2026. Eligible studies assessed depression, depressive symptoms, anxiety, generalised anxiety disorder (GAD), or PTSD-related symptoms alongside inflammatory biomarkers in blood or saliva and/or oral microbiome profiles. Reference lists of key eligible studies were also screened. Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) or an adapted NOS framework.

Fifty-three primary studies met eligibility criteria, including 42 studies evaluating inflammatory or salivary biomarkers and 11 studies examining oral microbiome profiles. Depression was associated with alterations in pro-inflammatory markers, particularly CRP, IL-6-related signalling, TNF-α, and other cytokine or chemokine markers. Anxiety-related findings were more heterogeneous. Oral microbiome studies reported altered community composition and taxa associated with depression, anxiety, and trauma-related symptoms, but findings varied by population, sampling site, and adjustment for oral-health and behavioural confounders.

Current evidence suggests depression and anxiety-related conditions are associated with low-grade inflammatory activity and alterations in the oral microbiome. These findings support an oral-immune-brain framework for future research, but the current evidence remains largely observational.