Oral microbiota dysbiosis alters chronic restraint stress-induced depression-like behaviors by modulating host metabolism

May 19, 2024Pharmacological research

Changes in mouth bacteria may affect stress-related depression behaviors by altering body metabolism

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Abstract

Oral microbial and metabolic signatures were significantly different between 87 patients with depressive symptoms and 70 healthy controls.

Germ-free mice transplanted with saliva from chronic stress-exposed mice exhibited depression-like behavior and oral microbial dysbiosis.
The oral microbiota dysbiosis was marked by a significant increase in Pseudomonas, Pasteurellaceae, and Muribacter, alongside a decrease in Streptococcus.
Metabolomic analysis revealed altered plasma metabolites, particularly an increase in Eicosapentaenoic Acid in mice exposed to chronic stress.
Oral and gut barrier dysfunction from chronic stress-induced dysbiosis may be linked to increased blood-brain barrier permeability.
Supplementation with Pseudomonas aeruginosa worsened depression-like behavior, while treatment with Eicosapentaenoic Acid showed protective effects.

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Studies have shown that the microbiota-gut-brain axis is highly correlated with the pathogenesis of depression in humans. However, whether independent oral microbiome that do not depend on gut microbes could affect the progression of depression in human beings remains unclear, neither does the presence and underlying mechanisms of the microbiota-oral-brain axis in the development of the condition. Hence this study that encompasses clinical and animal experiments aims at investigating the correlation between oral microbiota and the onset of depression via mediating the microbiota-oral-brain axis. We compared the oral microbial compositions and metabolomes of 87 patients with depressive symptoms versus 70 healthy controls. We found that the oral microbial and metabolic signatures were significantly different between the two groups. Significantly, germ-free (GF) mice transplanted with saliva from mice exposing to chronic restraint stress (CRS) displayed depression-like behavior and oral microbial dysbiosis. This was characterized by a significant differential abundance of bacterial species, including the enrichment of Pseudomonas, Pasteurellaceae, and Muribacter, as well as the depletion of Streptococcus. Metabolomic analysis showed the alternation of metabolites in the plasma of CRS-exposed GF mice, especially Eicosapentaenoic Acid. Furthermore, oral and gut barrier dysfunction caused by CRS-induced oral microbiota dysbiosis may be associated with increased blood-brain barrier permeability. Pseudomonas aeruginosa supplementation exacerbated depression-like behavior, while Eicosapentaenoic Acid treatment conferred protection against depression-like states in mice. These results suggest that oral microbiome and metabolic function dysbiosis may be relevant to the pathogenesis and pathophysiology of depression. The proposed microbiota-oral-brain axis provides a new way and targets for us to study the pathogenesis of depression.

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Oral microbiota dysbiosis alters chronic restraint stress-induced depression-like behaviors by modulating host metabolism

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