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Patient-derived Enterococcus mundtii and its capsular polysaccharides cause depression through the downregulation of
Min-Kyung Joo1, Xiaoyang Ma1, Jong-Wook Yoo1
1Neurobiota Research Center and Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul 02447, South Korea.
Abstract:
The genus Enterococcus is commonly overpopulated in patients with depression compared to healthy control in the feces. Therefore, we isolated Enterococcus faecalis, Enterococcus durans, Enterococcus gallinarum, Enterococcus faecium, and Enterococcus mundtii from the feces of patients with comorbid inflammatory bowel disease with depression and examined their roles in depression in vivo and in vitro. Of these Enterococci, E. mundtii NK1516 most potently induced NF-κB-activated TNF-α and IL-6 expression in BV2 microglia cells. NK1516 also caused the most potent depression-like behaviors in the absence of sickness behaviors, neuroinflammation, downregulated brain-derived neurotrophic factor (BDNF), and serotonin (5-HT) levels in the hippocampus of mice. Furthermore, E. mundtii NK1516 reduced the mRNA expression of Htr1a in the hippocampus. Its capsular polysaccharide (CP), but not cytoplasmic components, also caused depression-like behaviors and reduced BDNF and serotonin levels in the hippocampus. Conversely, this was not observed with E. mundtii ATCC882, a well-known probiotic, or its CP. Orally gavaged fluorescence isothiocyanate (FITC)-conjugated NK1516 CP was detected in the hippocampus of mice. The NK1516 genome exhibited unique CP biosynthesis-related genes (capD, wbjC, WecB, vioB), unlike that of ATCC882. These findings suggest that E. mundtii may be a risk factor for depression.
Insights
Certain Enterococcus strains, particularly Enterococcus mundtii, may contribute to depression. Research found E. mundtii induced depression-like behaviors and altered brain chemicals in mice, suggesting it could be a depression risk factor.
Area of Science:
- Microbiology
- Neuroscience
- Immunology
Background:
- Enterococcus bacteria are often found in higher numbers in the gut of individuals with depression.
- Comorbidities like inflammatory bowel disease (IBD) can be present alongside depression.
Purpose of the Study:
- To investigate the potential role of specific Enterococcus species, isolated from IBD and depression patients, in the development of depression.
- To identify specific bacterial components responsible for depression-inducing effects.
Main Methods:
- Isolation and identification of Enterococcus species from patient fecal samples.
- In vitro assessment of bacterial effects on microglial cells (NF-κB, TNF-α, IL-6).
- In vivo studies in mice to evaluate depression-like behaviors, neuroinflammation, brain-derived neurotrophic factor (BDNF), and serotonin levels.
- Analysis of bacterial capsular polysaccharide (CP) effects and genetic comparison.
Main Results:
- Enterococcus mundtii NK1516 most significantly induced inflammatory markers (TNF-α, IL-6) in microglia.
- E. mundtii NK1516 caused depression-like behaviors in mice without sickness behaviors or neuroinflammation.
- NK1516 reduced hippocampal BDNF and serotonin levels and altered Htr1a mRNA expression.
- The capsular polysaccharide (CP) of NK1516, but not cytoplasmic components or E. mundtii ATCC882 CP, induced these effects.
- Unique CP biosynthesis genes were identified in NK1516 compared to ATCC882.
Conclusions:
- Enterococcus mundtii, specifically strain NK1516, may act as a risk factor for depression.
- The capsular polysaccharide of E. mundtii NK1516 appears to be a key factor in its depression-inducing effects.
- Further research into E. mundtii's role in gut-brain axis disorders is warranted.
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