The role of microbiota - oral - brain axis in anxiety and depression

Abstract Background: The gut microbiota plays a vital role in mental disorders, and the gut-brain axis has also been studied in the pathogenesis of depression. Furthermore, studies show the presence of the oral-gut microbiome axis. Oral microbiota dysbiosis is linked with mental disorders, suggesting that pathologic bacteria from the oral cavity may contribute to the development of mental disorders. However, whether independent oral microbiome that do not depend on gut microbes impacts the progression of depression, andthe presence and mechanism underlying about the microbiota-oral-brain axis in depression remains unclear. Here, saliva microbiota transplantation in germ-free mice used to study the impacts and mechanism of oral microbes on depression. 16S rRNA sequencing and liquid chromatography/mass spectrometry were performed on saliva, stool and serum to investigate alterations in microbiota and metabolites. Results: It was observed that differential shaping effect of oral and intestinal microbiota on depression. Moreover, germ-free mice transplanted with saliva from chronic restraint stress (CRS)-exposed mice displayed emotional impairment and oral microbial dysbiosis with significant differential abundance of bacterial species including the enrichment of Pseudomonas, Pasteurellaceae and Muribacter and depletion of Streptococcus. Metabolomic analysis showed the alternation of metabolites in the serum of CRS-exposed germ-free mice, especially Eicosapentaenoic Acid. Furthermore, ectopic colonization of oral microbiome induced by CRS in the intestine impaired gut barrier function, which is associated with increased blood-brain barrier permeability. Pseudomonas supplementation exacerbated depression-like behavior, while Eicosapentaenoic Acid treatment conferred protection against depression-like states in mice. Conclusions: These results suggest the external shaping process of gut microbiota by oral microbiome and indicate the great value of oral saliva samples in monitoring and assessing depression progression in clinical settings.