Gut Microbiome and Sleep Disorders

Sleep is one of the most fundamental functions of the human body. It directly affects our physical and mental health, concentration, immune function, and hormonal regulation. However, in an era overloaded with stimuli and stress, sleep disorders such as insomnia, shallow sleep, or early awakening are becoming increasingly common.

Until recently, medical interventions focused almost exclusively on the brain, sleep habits, or psychological factors. However, a different field of research has emerged with notable findings: the gut microbiome.

The communication between the gut and the brain, known as the gut-brain axis, affects not only mood and anxiety but also the circadian rhythm and sleep quality. The microbiome influences the regulation of neurotransmitters such as serotonin and produces metabolites, including short-chain fatty acids (SCFAs), that affect our mood, circadian rhythm, and the sleep-wake cycle. Probiotic strains, such as Lactobacillus reuteri, may improve sleep disorders by producing gamma-aminobutyric acid (GABA), a neurotransmitter with anxiolytic effects.

Long before we turn to pharmacotherapy, it's worth exploring whether the underlying cause of our insomnia lies in the gut. This is precisely what functional medicine does: it approaches symptoms not as isolated phenomena, but as manifestations of deeper disruptions in the body's homeostasis.

The gut is not just our "second brain." It is an active regulator of sleep, mood, and our overall well-being. If you're experiencing sleep disturbances, it's time to ask whether - and through which biological mechanisms - the gut microbiome might be at the root of the problem, how to investigate it, and, of course, what practical steps you can take in your daily life to address this type of disorder.

Gut-Brain Axis: A Dynamic Bidirectional Relationship

The gut microbiome consists of trillions of microorganisms that mainly reside in the large intestine. These microorganisms are not merely “co-inhabitants” of our body. They interact closely with our cells and actively participate in crucial functions such as digestion, vitamin production, immune regulation, and even the neurochemical balance of the brain.

Communication between the gut and brain occurs via:

Neuronal pathways, mainly the vagus nerve
Hormonal signals, including cortisol, melatonin, and serotonin
Immune mechanisms, such as the production of cytokines
Microbiome metabolites, which act both locally and systemically

This bidirectional relationship is also known as the gut-brain axis. When the balance of the gut microbiome is disrupted - a condition called dysbiosis - it affects not only digestion but also psychological and cognitive function, including sleep.

The Role of Serotonin and Melatonin

90% of serotonin, the neurotransmitter of pleasure and mood regulation, is produced in the gut. Serotonin is a precursor of melatonin, the primary hormone that regulates the circadian rhythm and the onset of sleep. When the microbiome is out of balance, the production of these substances may be reduced or disrupted.

Research has shown that certain bacteria, specifically strains such as Bifidobacterium and Lactobacillus, enhance serotonin production. At the same time, metabolites such as short-chain fatty acids (SCFAs), produced by bacteria that degrade plant fibers, have protective effects on the blood-brain barrier and exert overall anti-inflammatory activity.

Dysbiosis and Inflammation: The Enemy of Sleep

Chronic low-grade inflammation caused by a disrupted microbiome can affect neurotransmitter activity in the brain, melatonin production, and hypothalamic function, the brain’s primary sleep-regulatory center. At the same time, recent studies have shown a correlation between elevated levels of pro-inflammatory cytokines (e.g., IL-6 and TNF-α) and poor sleep quality.

Additionally, microbiome imbalance has been linked to changes in circadian rhythm, mainly due to disrupted gene expression in both the gut and the brain, as well as activation of the HPA axis (hypothalamus-pituitary-adrenal), resulting in elevated cortisol levels. All of the above lead to a state of hyperarousal (both physical and mental) that manifests as difficulty falling or staying asleep.

The disruption of the microbiome is not just a digestive issue. It is a multifaceted biological imbalance that affects the brain, mood, neurotransmitter function, and ultimately the very structure and quality of sleep.

The Functional Approach to Sleep Quality: Searching for Deeper Causes

Functional medicine addresses health problems with the aim of identifying and treating the root cause of dysfunction, rather than merely managing the symptoms it produces. In the case of sleep disorders, this means asking:

What underlying problems are leading to insomnia?
Are there biochemical imbalances that promote alertness instead of relaxation?
What’s going on with the circadian rhythm, stress hormones, and gut health?

The answer often lies in the microbiome, inflammation, and neuroendocrine regulation. The functional investigation of sleep disorders involves specific diagnostic tests that provide a holistic view of the body’s health status:

1. Melatonin Sulfate: A specialized measurement of the main melatonin metabolite in urine, revealing the circadian pattern of its production. Melatonin is a key regulator of sleep and wakefulness, and it is directly influenced by the condition of the gut microbiome via the gut-brain axis.

2. EnteroScan®: A molecular analysis of the gut microbiome that examines the balance between beneficial and potentially pathogenic bacteria, the levels of specific metabolites (such as SCFAs), as well as inflammatory markers and gut permeability indicators.

3. NutriScan® Vitamin Profile & NeuroScan® Neurotransmitter Profile: Through the NutriScan^® group of tests, potential vitamin deficiencies required for neurotransmitter synthesis are detected. For example, Vitamin B6, B12, and folic acid are involved in methylation and serotonin synthesis, while Vitamin D is linked to sleep regulation and immune function. In parallel, the levels of major neurotransmitters (e.g., serotonin and GABA) can be measured in the urine.

4. AdrenalScan®: A specialized test of adrenal function by analyzing the daily saliva profile of cortisol and DHEA-S. An inverted cortisol profile (high cortisol at night, low in the morning) is a frequent finding in individuals with insomnia.

5. Chronic Inflammation Panel (ImmuneScan®): Measuring inflammatory markers is critical, as systemic inflammation affects both neurotransmitter action and the structure of sleep. For instance, elevated IL-6 levels have been linked to insomnia, chronic fatigue, and REM sleep disturbances.

Insomnia is not just a matter of mental hyperactivity. It is often a biochemical disorder rooted in the gut. Every individual has a unique microbial identity, different stress resilience, and distinct hormonal balances. That’s why treatment must be based on personalized data, not generic guidelines.

The functional approach to sleep disorders combines lab testing with clinical assessment, looks for dysfunction patterns (e.g., inflammation, leaky gut, coenzyme deficiencies), and aims to restore body function through gentle, personalized interventions that respect the body’s physiology.

Microbiome and Sleep: Practical Steps You Can Apply Today

Restoring microbial balance doesn’t always require pharmaceutical interventions. Often, targeted changes in diet and lifestyle are enough to support the microbiome and create the right conditions for natural sleep. Below are key strategies based on functional medicine insights and recent scientific literature:

Nutrition: Nourishment for the Microbiome and Hormonal Sleep Balance.
Gut health and the body’s ability to synthesize melatonin and serotonin largely depend on nutritional support. The approach focuses on three main areas:

1. Prebiotic & Probiotic Foods. Supporting the gut microbiome is the foundation for regulating the gut-brain axis.

Prebiotic foods (plant fibers that feed good bacteria): Artichoke, garlic, leek, onion, banana, apple with skin, oats, flaxseed, root vegetables. They help increase the production of SCFAs, which have anti-inflammatory effects and are associated with better sleep.
Probiotic foods (live microorganisms that positively influence the microbiome): Yogurt with live cultures, kefir, fermented vegetables (sauerkraut, kimchi), apple cider vinegar. Specific strains like Lactobacillus reuteri and Bifidobacterium longum are linked to increased GABA production, a neurotransmitter that calms the brain.

2. Nutritional Support for the Tryptophan–Serotonin–Melatonin Pathway. Tryptophan is the precursor of melatonin and is essential for the body’s hormonal preparation for sleep. Tryptophan-rich foods include:

Turkey, chicken, eggs
Cheese, yogurt
Nuts, pumpkin seeds
Oats, banana

For optimal absorption, combine with carbohydrates (e.g., rice, sweet potatoes), which facilitate tryptophan transport to the brain.

3. Anti-Inflammatory Diet for Lower Nighttime Cortisol. Inflammation is a major inhibitor of sleep. An anti-inflammatory diet reduces cortisol activity and supports recovery.

Foods to avoid: Sugar, refined flours, trans fats, seed oils, processed and red meats (in excess)
Foods to emphasize: Fatty fish (omega-3), olive oil, ginger, turmeric, colorful fruits and vegetables (rich in antioxidants)

Circadian Rhythm Regulation Through Lifestyle Habits
Our body follows an internal 24-hour rhythm, regulated by light, temperature, and hormonal flow. Practical steps to support it include:

Morning exposure to natural light. Ideally, 15-20 minutes without sunglasses to help synchronize the biological clock.
Limiting artificial lighting and screens after sunset. Blue light suppresses melatonin production and delays sleep onset.
Consistent sleep and wake times, even on weekends. Helps stabilize the circadian rhythm and improve sleep depth.
Evening walk or light physical activity. Promotes discharge of the sympathetic nervous system and prepares the body for rest.

Maintaining circadian rhythm stability is associated with deeper, uninterrupted sleep and lower nighttime cortisol levels.

Support with Supplements
Supplement use is not always necessary, but it can be supportive when based on laboratory findings, clinical data, and tailored to an individual’s specific needs. Potential recommendations include:

Magnesium: Regulates neuromuscular excitability and calms the central nervous system (CNS)
Melatonin: For short-term use and always under supervision
5-HTP or L-Tryptophan: Enhance serotonin production, supporting mood and sleep regulation
GABA: Assists sleep onset, especially when anxiety is present
Specialized probiotics (Lactobacillus, Bifidobacterium): Help regulate the gut-brain axis

All the above interventions should be used only after evaluation of laboratory markers and a personalized assessment by qualified health professionals. Empirical use of supplements or dietary changes without a diagnosis carries the risk of ineffectiveness or adverse effects.

Conclusion: The Gut as a Key to Deep Rest

Sleep disorders are rarely random. They’re not solely caused by stress, habits, or external conditions. Often, they are the result of an imbalance rooted in the microbiome, inflammation, and disruption of the natural biological rhythm.

Modern science urges us to view sleep as a multifactorial biological phenomenon, influenced by environment, nutrition, stress, and, most importantly, the organism’s functional cohesion. This is exactly the foundation of functional medicine: understanding the body as a unified and dynamic system.

If you're experiencing:

Insomnia or fragmented sleep
Difficulty relaxing at night
Unexplained fatigue, even after “enough” sleep
Psychological tension or irritability
Frequent awakenings without obvious reason

…then it’s time to ask whether the problem starts in the gut.

What You Can Do Today:

Discover what’s really going on in your body with an EnteroScan®, a specialized functional microbiome test that reveals valuable insights into your gut balance.
See how Functional Medicine can help you in practice, by identifying root causes instead of just masking symptoms.
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References

Xu, H., Zhang, Y., & Li, J. (2025). Microbiota metabolites affect sleep as drivers of brain-gut communication (Review). International Journal of Molecular Medicine, 56(3). https://doi.org/10.3892/ijmm.2025.5571
Zhao, W., Fang, C., & Zhang, X. (2025). Lactobacillus reuteri E9 regulates sleep disorders through its metabolite GABA. Frontiers in Bioscience, 30(6), 39587. https://doi.org/10.31083/FBL39587
Tai, W. C., Li, Y., & Chen, M. (2025). Tryptophan-fructooligosaccharides combination improves sleep in mice via anti-inflammation and gut microbiota modulation. Food & Function, 16(17), 6848–6860. https://doi.org/10.1039/d5fo01651g

At Diagnostiki Athinon, we treat prevention with the seriousness it deserves. This is where science meets personalized care.