How an Oral Bacterium Influences Sleep in Depression
For decades, depression has been viewed primarily as a brain disorder, treated with medications that alter brain chemistry. Meanwhile, sleep disturbances have been considered one of its many symptoms. But what if a key to understanding this connection lay not in the brain, but in the human mouth?
Emerging research reveals an unexpected player in depression-related sleep problems—a common oral bacterium called Haemophilus. Recent scientific investigations have uncovered a potential pathway where imbalances in oral bacteria may drive sleep disturbances in people with major depressive disorder (MDD) through their effect on brain inflammation 1 2 3 .
This discovery represents a significant paradigm shift in how we understand mental health, suggesting that the oral microbiome—the community of microorganisms living in our mouths—may actively influence brain function and sleep patterns through complex biological pathways.
Before delving into the specific research, it's important to understand the ecosystem in question. The human mouth hosts one of the most diverse microbial communities in the body, comprising over 700 species of bacteria 4 . Under normal circumstances, these microorganisms coexist peacefully, contributing to oral health. However, when this delicate balance is disrupted—a state known as oral dysbiosis—the consequences may extend far beyond the mouth.
The oral cavity's significant vascularity and frequent exposure to bacteremia (bacteria in the bloodstream) position it as a pivotal area where the microbiome can influence various systemic diseases 4 . The microorganisms in our mouth can affect distant organs through several potential routes:
Through the bloodstream, allowing oral bacteria to reach distant organs including the brain.
Triggering immune responses throughout the body that can affect brain function.
Influencing stress response systems that regulate both mood and sleep.
Through swallowed oral bacteria that can alter the gut-brain axis 7 .
These pathways form what scientists call the "oral-brain axis," a communication network between oral bacteria and brain function that may play a crucial role in mental health conditions.
A landmark study published in 2025 set out to specifically investigate the role of oral bacteria in sleep disturbances among MDD patients 1 2 . The research team recruited 68 participants—38 MDD patients experiencing significant sleep disturbances and 30 healthy controls 1 2 .
The researchers employed a comprehensive approach:
Detailed sleep and depression evaluations using standardized tools
Sterile cotton swabs from the tongue dorsum of all participants
16S rRNA gene sequencing to identify bacterial species
| Assessment Tool | Purpose | What It Measures |
|---|---|---|
| Pittsburgh Sleep Quality Index (PSQI) | Evaluate sleep quality | Seven domains of sleep including quality, latency, duration, and efficiency |
| 24-item Hamilton Depression Scale (HAMD-24) | Assess depressive symptoms | Severity of various depressive symptoms |
| HAMD Sleep Disturbance Subscore | Quantify sleep problems | Specific sleep-related items from the HAMD scale |
The analysis revealed fascinating differences between the oral microbiomes of MDD patients and healthy controls. Four oral bacterial genera showed significant changes: Solobacterium, Granulicatella, Campylobacter, and most notably, Haemophilus 1 2 .
The crucial findings centered on Haemophilus:
| Clinical Measure | Correlation with Oral Haemophilus | Statistical Significance |
|---|---|---|
| PSQI Score | Negative Correlation | Significant |
| HAMD-24 Score | Negative Correlation | Significant |
| PSQI Score Change After Treatment | Positive Correlation | Significant |
| HAMD-24 Score Change After Treatment | Positive Correlation | Significant |
How exactly might oral bacteria influence brain function and sleep? The research points to neuroinflammation as a key mechanism 1 6 .
The study found that GFAP—a protein released by activated astrocytes in the brain—mediated the relationship between oral Haemophilus and sleep disturbances 1 . This suggests a potential pathway where oral bacteria may influence brain inflammation, which in turn disrupts sleep regulation.
Under normal conditions, physiological sleep involves a complex interplay with the immune system 6 . Early sleep is characterized by increased innate immunity and pro-inflammatory processes, while late sleep transitions to anti-inflammatory responses 6 . When this delicate balance is disrupted by excessive neuroinflammation, normal sleep architecture can be compromised.
Reduced levels of beneficial bacteria like Haemophilus in the oral microbiome.
Oral bacteria or their byproducts enter circulation, triggering immune responses.
Inflammatory mediators increase permeability, allowing immune cells and cytokines to enter the brain.
Brain immune cells (astrocytes) become activated, releasing GFAP and other inflammatory markers.
Neuroinflammation interferes with normal sleep-wake regulation in brain regions like the hypothalamus.
Resulting in poor sleep quality, insomnia, and non-restorative sleep characteristic of depression.
This neuroinflammatory pathway may explain why MDD patients with oral dysbiosis experience more significant sleep disturbances and why they might respond less effectively to conventional antidepressants that don't target this inflammatory component.
This research on Haemophilus fits into a growing body of evidence connecting oral health to mental wellbeing:
A 2024 study analyzing data from 4,692 participants found that oral microbiome diversity moderates the relationship between sleep duration and depression risk 4 .
A 2021 study discovered significant differences in the salivary microbiome of young adults with depression compared to healthy controls 8 .
A 2025 systematic review of eleven studies concluded that oral microbiome dysbiosis is significantly associated with depression 5 .
| Bacterial Genus | Change in Depression | Study Reference |
|---|---|---|
| Haemophilus | Decreased | Frontiers in Cellular and Infection Microbiology (2025) |
| Neisseria | Increased | Scientific Reports (2021) |
| Prevotella nigrescens | Increased | Scientific Reports (2021) |
| Spirochaetaceae | Increased | Journal of Clinical Medicine (2025) |
| Actinomyces | Increased | Journal of Clinical Medicine (2025) |
Understanding this field requires familiarity with the essential tools researchers use to investigate the oral microbiome:
This statistical approach helps determine whether a variable (like neuroinflammation) serves as an intermediate step between two other variables (oral bacteria and sleep disturbances) 1 .
This research opens up exciting possibilities for improving mental health treatment:
Oral microbiome analysis could provide a non-invasive method for identifying depression subtypes characterized by sleep disturbances 5 .
Assessing a patient's oral microbiome might help predict their response to different antidepressants, allowing for more tailored treatment plans 1 .
These findings suggest potential for interventions targeting the oral microbiome, such as probiotics or specialized oral care regimens 5 .
The discovery of a potential link between oral Haemophilus, neuroinflammation, and sleep disturbances in MDD patients represents a significant shift in how we conceptualize mental health. It suggests that effective depression treatment might one day involve not just psychiatrists and psychologists, but also dentists and oral care specialists.
As research in this field advances, we may be moving toward a more holistic understanding of mental health that acknowledges the profound connections between different systems in our body—from the bacteria in our mouths to the inflammatory processes in our brains that regulate our sleep and mood.
While it's too early to recommend specific oral health interventions for depression, this research underscores the importance of comprehensive healthcare that considers all aspects of our biology in the quest for better mental wellbeing.