Oral microbiome dysbiosis, neuroinflammation, and psychiatric disorders: A review of current progress

Table 1 Studies on the oral-brain axis in psychiatric conditions

Evidence type	Research type	Key findings	Relevance to psychiatry	Evidence level/limitations	Ref.
Animal study	Mouse model	Administration of Lactobacillus in mouse models improves hypoxia-induced anxiety/depressive-like behaviors	Providing exploratory evidence for the gut-brain axis	Animal model; behavioral endpoints do not equate to clinical diagnosis	Chang et al[1], 2025
Meta analysis	Systematic review and meta-analysis of 33 studies	Patients with severe mental illness show poorer oral hygiene habits (odds ratio for tooth brushing = 0.19)	Confirms a clinical association, but findings are largely driven by behavioral factors	Cross-sectional in nature; multiple potential confounders	Turner et al[17], 2022
Mechanistic study (animal)	Mouse depression model	LPS activates microgram, triggering neuroinflammation and depressive-like behaviors	Highlights neuroinflammation as a possible mediating pathway	Animal model; LPS injection does not fully recapitulate oral microbial translocation	Zhao et al[32], 2024
Mechanistic study (animal)	Mouse model	Periodontitis promotes bacterial extracellular vesicles that induce neuroinflammation in the brain and trigeminal ganglion	Suggests a potential mechanism via the trigeminal nerve pathway	Animal model; findings require validation in psychiatric populations	Ha et al[30], 2023
Clinical association	Systematic review and meta-analysis	Oral microbiome composition is significantly altered in patients with psychiatric disorders	Confirm a stable association between oral microbiota and psychiatric conditions	Predominantly cross-sectional studies; high heterogeneity across studies	Cao et al[14], 2025
Clinical association	Review	Mental health status is associated with periodontal and peri-implant disease	Supports clinical relevance of the oral-systemic link	Review article; no original data presented	Ball and Darby[13], 2022
Mechanistic	Review	Periodontitis may affect the brain through neuroinflammatory mechanisms	Indirectly supports the oral-neuroinflammation connection	Review article; lacks primary experimental evidence	Li et al[10], 2022
Clinical observation	Prospective commentary	Mental disorders are associated with oral diseases, with a proposed bidirectional relationship	Introduces the hypothesis of bidirectionality	Opinion piece; not based on original empirical	Joury et al[12], 2023

LPS: Lipopolysaccharide.