Dysbiosis and Sleep Problems in ME/CFS: The Gut-Brain Connection
The Link Between Gut Health and Sleep Disturbances
Sleep is essential for overall health and is closely connected to both the immune system and gut microbiota. Research suggests that gut bacteria play a significant role in regulating sleep through metabolic signals that influence the entire body. Studies show that disruptions in gut microbiota are often associated with sleep disturbances. These findings are particularly relevant for individuals with postviral conditions, where both gut health and sleep are commonly affected.
Sleep Disturbances in Postviral Conditions
Studies report that approximately 50% of individuals with ME/CFS experience sleep disorders, including non-restorative sleep, restlessness, insomnia, and sleep apnea. Research also indicates that individuals with fibromyalgia experience lower sleep quality, longer wake times after sleep onset, shorter sleep duration, and greater difficulty initiating sleep.
For individuals recovering from COVID-19, studies have found that insomnia can persist months after the acute phase of the infection. The term ‘coronasomnia’ has been coined to describe the high prevalence of sleep disorders in long COVID, with up to 45% of those affected experiencing sleep disruptions (Pena, et al. 2023).
Since gut dysbiosis is common in these patients, an important question remains: Do sleep problems worsen dysbiosis, or does dysbiosis contribute to sleep problems?
The Gut-Sleep Connection: Cause or Effect?
At first glance, the relationship between the gut and sleep may not seem obvious, but research shows they are deeply connected. Studies have found that gut microbiome diversity directly impacts sleep quality.
A 2023 study by King’s College London and other institutions, in partnership with the personalized nutrition company Zoe, found that irregular sleep patterns were linked to an increase in unfavorable gut bacteria associated with poor health outcomes (Bermingham, et al. 2023).
A Bidirectional Relationship
The question remains: Does gut dysbiosis cause sleep disturbances, or do disrupted sleep patterns alter the gut microbiome? Likely, both factors influence each other in a feedback loop:
Poor sleep increases stress and cortisol levels, which weaken the gut barrier and encourage microbial imbalances.
A less diverse gut microbiome reduces the production of sleep-promoting metabolites, such as butyrate, while increasing pro-inflammatory bacteria, both of which can negatively impact sleep quality.
Butyrate: A Bacterial-Derived Sleep-Promoting Signal
Rapid Eye Movement (REM) Sleep Behavior Disorder is associated with a loss of gut bacteria that produce butyrate, an anti-inflammatory short-chain fatty acid.
Low butyrate-producing bacteria have been identified in postviral conditions and fibromyalgia.
A 2019 mouse study found that administering butyrate had significant sleep-promoting effects (Szentirmai, et al. 2019).
These findings indicate that butyrate-producing gut bacteria play a crucial role in sleep regulation.
The Microbiome-Gut-Brain Axis (MGBA) and Sleep Regulation
The microbiome-gut-brain axis (MGBA) is a communication system between the gut and brain that helps regulate sleep. It functions through gut bacteria, which produce compounds that influence brain function, such as short-chain fatty acids (SCFAs), vitamins, and neurotransmitters.
Serotonin and Melatonin: Key Sleep Regulators
90% of the body's serotonin is produced in the gut.
Serotonin is essential for melatonin production, which controls the sleep-wake cycle.
Certain gut bacteria directly influence melatonin levels, reinforcing the strong connection between gut health and sleep (Neroni, et al. 2021).
Neurotransmitters That Impact Sleep
Gamma-aminobutyric acid (GABA): Helps relaxation and supports melatonin production.
Glutamate: Plays a role in the sleep process.
These interactions highlight how gut bacteria influence circadian rhythms and sleep regulation (Garvey, 2023).
Cytokines: The Inflammatory Link Between Sleep and the Gut
Cytokines are small proteins that regulate the immune system and play a key role in sleep and gut health.
IL-1β and IL-6: Two Critical Cytokines
IL-1β promotes sleep, but high levels can cause fatigue and disrupt deep, restorative sleep.
IL-6 levels rise when sleep is disrupted, creating a cycle where poor sleep fuels inflammation, worsening sleep quality.
Elevated Cytokines in ME/CFS
Both IL-1β and IL-6 tend to be elevated in ME/CFS, contributing to fatigue and sleep problems. Gut dysbiosis further exacerbates this cycle by increasing inflammation.
A 2019 study found that individuals with greater gut microbiome diversity had better sleep quality, including longer sleep times, better sleep efficiency, and reduced nighttime wakefulness (Smith, et al. 2019).
The Hypothalamus, Viral Infections, and Sleep Disruptions
The hypothalamus is a key brain region that regulates sleep. Some viral infections, including SARS-CoV-2, may infect neurons in the hypothalamus, leading to chronic sleep disturbances.
How Viruses Affect Sleep Centers
SARS-CoV-2 may enter the hypothalamus via the olfactory bulb.
Other viruses, such as Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and enteroviruses, which have been linked to ME/CFS onset, may also impact hypothalamic function.
Orexin and Sleep-Wake Regulation
Orexin, produced by the hypothalamus, regulates wakefulness.
Viral infections and neuroinflammation can damage orexin-producing neurons, which do not regenerate.
Orexin loss is linked to fragmented sleep and REM sleep dysregulation (Abdelmissih, 2022).
Conclusion: Restoring Gut Health to Improve Sleep
It remains unclear whether neuroinflammation and sleep disturbances drive gut dysbiosis, or if gut dysbiosis is the primary driver of sleep problems. What is clear is that:
Low orexin levels, IL-1β and IL-6 elevation, reduced butyrate, and poor microbiome diversity all contribute to sleep disturbances in postviral conditions.
There is a strong interplay between these factors, creating a cycle of poor sleep and gut dysfunction.
Modifiable Factors: Restoring Microbiome Health
Dietary changes can increase butyrate levels:
Consuming high-fiber foods and resistant starch.
Intermittent fasting has been shown to boost butyrate production.
Addressing neuroinflammation is also crucial. Some supplements that cross the blood-brain barrier may help reduce inflammation and improve sleep. Read more about neuroinflammation here.
References
1. Lupo GFD, Rocchetti G, Lucini L, et al. Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME). Sci Rep. 2021;11(1):7043. Published 2021 Mar 29. doi:10.1038/s41598-021-86425-6
2. Pena-Orbea C, Lapin B, Li Y, et al. Sleep Disturbance Severity and Correlates in Post-acute Sequelae of COVID-19 (PASC). J Gen Intern Med. 2023;38(8):2015-2017. doi:10.1007/s11606-023-08187-3
3. Bermingham KM, Stensrud S, Asnicar F, et al. Exploring the relationship between social jetlag with gut microbial composition, diet and cardiometabolic health, in the ZOE PREDICT 1 cohort. Eur J Nutr. 2023;62(8):3135-3147. doi:10.1007/s00394-023-03204-x
4. Szentirmai É, Millican NS, Massie AR, Kapás L. Butyrate, a metabolite of intestinal bacteria, enhances sleep. Sci Rep. 2019;9(1):7035. Published 2019 May 7. doi:10.1038/s41598-019-43502-1
5. Neroni B, Evangelisti M, Radocchia G, et al. Relationship between sleep disorders and gut dysbiosis: what affects what?. Sleep Med. 2021;87:1-7. doi:10.1016/j.sleep.2021.08.003
6. Smith RP, Easson C, Lyle SM, et al. Gut microbiome diversity is associated with sleep physiology in humans. PLoS One. 2019;14(10):e0222394. Published 2019 Oct 7. doi:10.1371/journal.pone.0222394
7. Abdelmissih S. A Bitter Experience That Enlightens the Future: COVID-19 Neurological Affection and Perspectives on the Orexigenic System. Cureus. 2022;14(10):e30788. Published 2022 Oct 28. doi:10.7759/cureus.30788
8. Garvey M. The Association between Dysbiosis and Neurological Conditions Often Manifesting with Chronic Pain. Biomedicines. 2023;11(3):748. Published 2023 Mar 1. doi:10.3390/biomedicines11030748
