In a recent study under review at the Microbiome journal and currently posted to the Research Square* preprint server, researchers in China used serum metabolomics, gut and oral microbiome investigations, as well as germ-free mice models to investigate the role of the oral-gut-brain axis in anxiety and depression.
Study: The role of microbiota - oral - brain axis in anxiety and depression. Image Credit: Stanislaw Mikulski / Shutterstock.com
*Important notice: Research Square publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
Background
Depression is a predominant mental health problem across the world and has been exacerbated in recent times due to the fear, drastic social changes, and economic burden associated with the coronavirus disease 2019 (COVID-19) pandemic. Statistics indicate that only a small percentage of individuals with depression receive adequate help or treatment and many cases remain undiagnosed. A more thorough understanding of the underlying mechanisms of depression could help develop appropriate treatment strategies.
Various studies have reported a connection between depression and the gut microbiome. In fact, various neurotransmitters including serotonin, γ- aminobutyric acid (GABA), and other metabolites secreted by gut microbes are known to interact with the central nervous system (CNS).
The gut microbiota is also impacted by microbes found in the oral cavity, with studies on inflammatory bowel disease (IBD) suggesting that the oral cavity could be a possible reservoir for intestinal pathobionts. Oral cavity microbes have also been linked to Alzheimer’s disease progression.
About the study
In the present study, researchers discuss the results of a cross-sectional analysis of a cohort consisting of individuals between the ages of 18 and 60 with depression and anxiety.
The participants’ mental health conditions were established based on greater than seven points on the Hamilton Anxiety Scale and Hamilton Depression Scale. A control cohort of healthy individuals with a score of lower than seven on the same scales was also included in the analysis.
All study participants were drug-naïve. Individuals with a history of schizoaffective or bipolar disorder, schizophrenia, diabetes, thyroid disease, chronic inflammatory disease, cardiovascular disease, acute intoxication, substance abuse, and antibiotic use in the last month, as well as pregnant or lactating individuals, were excluded. Saliva samples were obtained from all participants for metabolomic and microbiome analyses.
For the studies using animal models, normal and germ-free female Kunming mice were used for the chronic restraint test and subsequent oral microbiome transplantation tests. Following the transplantation of the oral microbiota, mice underwent various behavioral tests such as the forced swim, open-field, and tail suspension tests.
The 16s ribosomal ribonucleic acid (rRNA) was sequenced from deoxyribonucleic acid (DNA) extracted from the oral and fecal samples of the mice. Serum samples from both the participants and mice were also subjected to liquid chromatography-tandem mass spectrometry to identify the different metabolites.
Tissue samples from the mice were also used for Western blot analysis and immunofluorescent staining. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to amplify the Zonula occludens-1 (ZO-1), Occludin, and Claudin-1 genes. Colon tissue samples from the mice were also subjected to histological analyses and enzyme-linked immunosorbant assay (ELISA).
Results
The oral and gut microbiomes were found to have varying roles in the development of depression.
The oral microbial transplantation studies, where germ-free mice were transplanted with saliva from mice that underwent chronic restraint stress, revealed that germ-free mice exhibited signs of emotional impairment.
Furthermore, the oral microbiome of these mice was imbalanced, with significant differences in the abundance of bacterial species. To this end, species belonging to the genera Muribacter, Pasteurellaceae, and Pseudomonas were enriched, while the species diversity of Streptococcus in the oral microbiome was significantly lower in the oral microbiomes.
Additionally, serum metabolite levels also differed with respect to the oral microbiome composition. For example, eicosapentaenoic acid levels were lower when there was an abundance of Muribacter, Pasteurellaceae, Romboutsia, and Pseudomonas species, but higher when the oral microbiome had a higher diversity of Streptococcus, Rodentibacter, and Turicibacter species. Germ-free mice that received oral microbiota transplantation also exhibited low levels of eicosapentaenoic acid.
Mice that were supplemented with Pseudomonas displayed exacerbated behaviors of depression, while those supplemented with eicosapentaenoic acid appeared to be protected against depression-like states.
The entry of oral bacteria species into the intestine was also linked to inflammatory changes due to metabolic endotoxins. These results indicate that the microbiomes of the gut and oral cavity, as well as changes in derived metabolites based on the composition of these microbiomes, were linked to depression and anxiety.
Conclusions
Overall, the study findings establish a connection between the oral and gut microbiomes and symptoms of depression and anxiety. These observations also suggest a potential use of saliva samples in diagnosing and monitoring the progression of clinical symptoms of depression.
*Important notice: Research Square publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
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