How the gut microbiome affects sleep quality
The gut microbiota and sleep interact with each other in both directions through metabolic, neural, and immune pathways. Does this open the door to new therapeutic strategies for sleep disorders?
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About this article
What if there is a bidirectional relationship between sleep and the gut? To go beyond simple correlational studies1, this review delves into the literature on the microbiota-gut-brain axis and its role in sleep regulation to summarize the potential mechanisms linking the composition and function of the gut microbiota to sleep disorders.
18% The estimated prevalence of obstructive sleep apnea (OSA) in the adult population is 18%.
10% The estimated prevalence of insomnia in the adult population is 10%.
3% The estimated prevalence of restless legs syndrome (RLS) in the adult population is 3%.
Sleep Disorders and the Gut-Brain Axis
Different sleep disorders are associated with changes in the composition of the gut microbiota and its metabolites:
- Insomniacs show reduced microbial diversity, with (though results vary by study) a decrease in the abundance of certain bacteria (such as Ruminococcaceae) correlating with a decrease in their metabolites (fewer secondary bile acids, produced by bacteria from liver bile acids).
- There is also less diversity in patients suffering from obstructive sleep apnea, and (sidenote: Fecal Microbiota Transplantation (FMT) A therapeutic procedure to restore the gut microbiota by transferring fecal bacteria from a healthy donor to a recipient. ) from individuals suffering from hypoxia can disrupt the sleep cycles of healthy animals.
- Night work and jet lag also cause significant changes in the microbiota, increasing intestinal permeability and inflammation.
- Narcolepsy may be associated with an imbalance between immunosuppressive and immunostimulatory microorganisms.
- In the case of restless leg syndrome, the multiplication of bacteria in the small intestine may play a role.
Dysbiosis is also observed in sleep-related disorders: in major depressive disorders, the composition of the gut microbiota is associated with sleep quality; in Parkinson’s disease,
(sidenote:
Mendelian randomization
An approach that exploits natural genetic variation to test causal relationships between a biological factor (e.g., cholesterol, vitamin D, BMI) and a disease (e.g., heart attack). Researchers use genetic variants associated with the biological factor of interest (e.g., patients with alleles that increase LDL cholesterol vs. patients without) to test whether there is a causal relationship between the biological factor (LDL cholesterol) and the disease (heart attack). The random distribution of alleles in the population reduces biases (confounding factors, etc.), mimicking some of the advantages of a randomized trial.
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studies suggest a causal link with gut bacteria; in Alzheimer’s disease, sleep disturbances are directly related to the accumulation of beta-amyloid protein, in parallel with changes in the bacterial flora that could be potential diagnostic and even therapeutic biomarkers.
0,03% The estimated prevalence of narcolepsy in the adult population is 0.03%.
>50% More than one in 2 people with dementia (including Alzheimer’s disease) suffer from insomnia.²
Two-way communication
The review also highlights three main bidirectional communication pathways through which the gut-brain-microbiota axis coordinates sleep:
- Metabolic and endocrine pathways: secondary bile acids and (sidenote: Short chain fatty acids (SCFA) Short chain fatty acids (SCFA) are a source of energy (fuel) for an individual’s cells. They interact with the immune system and are involved in communication between the intestine and the brain. Silva YP, Bernardi A, Frozza RL. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front Endocrinol (Lausanne). 2020;11:25. ) produced by bacteria affect sleep through systemic circulation. In addition, the microbiota produces or regulates key molecules of the wake-sleep cycle, such as GABA, serotonin, tryptophan and melatonin.
- Neural pathways: gut bacteria and their metabolites interact with the gut nervous system and cooperate with vagal nerve pathways, influencing brain areas and circuits related to sleep. In addition, the microbiota and its metabolites modulate the stress response and the corticosterone rhythm, influencing wakefulness-related hyperactivity.
- Immune pathways: Sleep deprivation triggers systemic and gut inflammation, weakening the gut barrier and affecting the central nervous system.
Did you know?
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In high-income European countries, obstructive sleep apnea (OSA) is the most costly sleep disorder (€184 billion), followed by insomnia (€158 billion), restless legs syndrome (RLS) (€79 billion), narcolepsy (€905 million) and REM sleep behavior disorder (RBD) (€436 million). Direct and indirect costs account for 48% and 52% of the total, respectively, with no data available on informal care costs.3
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Sleep disorders are very common in people with Parkinson’s disease, with up to 98% of patients experiencing them at some point. REM sleep behavior disorder (RBD) is seen in about 46% of patients with Parkinson’s disease.
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Restless legs syndrome (RLS) affects 15-20% of patients with Parkinson’s disease, although early-onset RLS does not predispose to the later development of Parkinson’s disease. However, severe RLS may be an early warning sign of the disease.
Modifying the Microbiome to Improve Sleep
Since traditional methods of treating sleep disorders often involve side effects, microbiome-targeted therapies represent promising strategies:
- (sidenote: Probiotics Live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. FAO/OMS, Joint Food and Agriculture Organization of the United Nations/ World Health Organization. Working Group. Report on drafting guidelines for the evaluation of probiotics in food, 2002. Hill C, Guarner F, Reid G, et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11(8):506-514. ) can improve sleep by regulating neurochemical pathways and reducing stress hormone levels. Strains such as Lactobacillus and Bifidobacterium have shown clinical benefits in people suffering from insomnia and those who are stressed.
- (sidenote: Prebiotics Prebiotics are specific indigestible dietary fibres which have effects that are favourable to health. They are used selectively by the beneficial micro-organisms in the microbiota of individuals. Specific products combining probiotics and prebiotics are known as symbiotics. Gibson GR, Hutkins R, Sanders ME, et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol. 2017;14(8):491-502. Markowiak P, Śliżewska K. Effects of Probiotics, Prebiotics, and Synbiotics on Human Health. Nutrients. 2017;9(9):1021. ) and synbiotics (pre + probiotics) can improve subjective sleep ratings and increase deep sleep phases.
- FMT offers promising remission rates for insomnia, especially in patients suffering from long-term COVID or fibromyalgia.
Is science heading towards precision medicine in the field of sleep?
Is science heading towards precision medicine in the field of sleep?
