Abbreviations:
AD: Alzheimer's disease, 1, 2 LPS: Lipopolysaccharide, 1, 2 mMED: Modified Mediterranean diet, 2 NREM: Non-rapid eye movement, 1, 3 REM: Rapid eye movement, 1, 3 SCFA: short-chain fatty acids, 2 SWS: slow-wave sleep, 1, 3
Introduction
Sleep is essential to all living beings. All multicellular organisms from large mammals to simple life forms such as nematodes require sleep.1 The universal requirement of sleep emphasizes its importance. Sleep is necessary for the body to maintain and replenish its energy resources, rest, build and recover muscles, and remodel and strengthen synaptic functions to store information and create important connections.
Based on physiological criteria, sleep can be divided into two states 2: Non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. During NREM sleep the body regenerates tissues and strengthens the immune system, while during REM sleep, dreams and memory consolidation occurs.
Modern-day life can disrupt regular sleeping patterns. Studies reported that over 30% of individuals experience sleep problems.3,4 Sleep deprivation or disturbance affects the whole body and mind’s well-being. The sleep/wake cycle is necessary for the body to ensure its proper function. Sleep disturbances have a negative effect on the metabolism. Energy requirements are increased in an exhausted organism; consequently, sleep deprivation increases food consumption.5 The disruption of sleep has been documented to result in the desire for calorie-rich, fast sugar-releasing, unhealthy food choices.6 Hence, poor sleep fuels unhealthy eating habits.
Long-term consequences of sleep disruptions include increased morbidity and mortality. An observational study showed a significant effect of sleep deprivation and heart health. A sleep duration of fewer than six hours was associated with an increased risk of myocardial infarction compared to ‘normal’ sleepers (6-9 hours).7 Chronic diseases such as Alzheimer’s disease (AD), diabetes, and acute infections such as influenza and pneumonia are major causes of mortality in developed countries.8 Several studies have linked lower sleeping durations with higher all-cause mortality. The risk for non-cardiovascular/cancer-related diseases was significantly higher in participants who experienced lower sleep hours than participants with normal sleep hours.9,10 Individuals were more susceptible to viral infections when short of sleep.11 A higher incidence of diabetes was observed in short sleepers (>6 hours).12 Short sleepers also had a higher risk of developing dementia and AD compared to ‘normal’ sleepers (7-8 hours).13,14
Sleep can improve gut health
The human intestinal tract harbours a diverse and complex microbial community that plays a central role in human health. This indispensable microbial community is even referred to as an ‘invisible metabolic organ’.15 The commensal gut microbiota breaks down complex carbohydrates and proteins that the human stomach and intestines cannot decompose, allowing nutrients from food to be more effectively absorbed. Changes to the gut microbiome can have major consequences, both beneficial and harmful, to human health.
Diet is a key factor in modulating the composition of the gut microbiome. In animal studies, sleep disruptions resulted in the consumption of higher-calorie meals.6 A switch to an unhealthy diet impacts the health of the gut flora.16 Unhealthy eating habits change the microbiome composition, which further guides the consumption of more unhealthy food, which worsens sleep quality,17 creating a vicious cycle. A high-fat diet altered the gut microbiota and released high levels of bacterial lipopolysaccharide (LPS)-endotoxin.18 LPS diffuses into the circulatory system and promotes systemic pro-inflammatory responses and adipose tissue inflammation, which aggravates obesity.19 Obesity has been recognized as a significant health issue in western societies with a constantly increasing prevalence.20 On the other hand, a healthy diet with high-fiber content promotes the release of beneficial short-chain fatty acids (SCFAs), which reduce inflammation.19 A healthy diet has also been shown to benefit sleep. A modified Mediterranean diet (mMED) lowered the insomnia rate.21 17
The alteration of the gut microbiota (dysbiosis) has a far-reaching impact on one's health and well-being. The gut-brain axis is a bidirectional link between the gut microbiome and the central nervous system, neuroendocrine, and -immune system. In this way, gut microbiota can have a direct effect on mood and health. An association between gut microbiota and the development of AD, atherosclerosis, diabetes, and infectious diseases has been shown.22
Sleep can boost immune responses
The immune system’s function is to eliminate threats to the host’s health, be they pathogens, parasites, or foreign environmental substances.23 Sleep impacts how and how well the immune system performs its functions.
Sleep might have an important function to support the immune system in fighting acute infections. While sleeping, in particular during slow-wave sleep (SWS), a pro-inflammatory cytokine milieu is created which reduces the levels of the anti-inflammatory stress hormone cortisol.24 Cytokines play a crucial role in orchestrating immune responses and in the regulation of sleep. Cytokines receptors are not only present on immune cells but also in the brain and on neural cells.2520The pro-inflammatory cytokines IL-1β and TNF-α promote NREM sleep, by increasing SWS, while decreasing REM sleep.26 During fever responses, the amount of NREM sleep, in which energy is conserved, increased in rats.27 Sufficient sleep before rhinovirus exposure was correlated with better resistance. Participants who slept less than seven hours were 3 times more likely to develop a cold than the reference group with ‘enough’ sleep.23,28 Increased sleep during infection might preserve energy and promote immune responses to strengthen host defenses.
Longer sleep hours also benefited the development of vaccine-induced humoral immune responses. Elevated antibody titers (IgG and/or IgM) were observed after vaccination in participants with ‘enough’ sleep compared to sleep-deprived participants.29,30 Thus, sleep after vaccination enhanced the formation of adaptive immune responses.
Chronic sleep deprivation advances aging. Sleep deprivation is associated with shorter telomere length, a process that limits cell divisions and eventually causes apoptotic death. This replicative senescence also affects leukocytes, which could partly explain the impairment of the immune response.31
Conclusion
Sleep is crucial for good health. Not getting an adequate amount and undisrupted sleep increases the risk of weight gain, disease, and disorders. Sleep functions to preserve energy and warrant proper immune function. Poor sleep contributes to unhealthy eating, which negatively affects the gut microbiota. Via communication through the gut-brain axis, dysbiosis has a profound impact on overall health. Sufficient sleep reduces the risk of obesity, neurological disorders, chronic diseases such as diabetes, and acute infections. In short, sleep might be an easy, low-cost way to improve overall health and well-being.
References
1. Roth, T. C., Rattenborg, N. C. & Pravosudov, V. v. The ecological relevance of sleep: the trade-off between sleep, memory and energy conservation. Philosophical Transactions of the Royal Society B: Biological Sciences 365, 945–959 (2010).
2. Carley, D. W. & Farabi, S. S. Physiology of Sleep. Diabetes Spectr 29, 5 (2016).
3. Hwang, J. H. & Park, S. W. The relationship between poor sleep quality measured by the Pittsburgh Sleep Quality Index and smoking status according to sex and age: an analysis of the 2018 Korean Community Health Survey. Epidemiol Health 44, (2022).
4. Hinz, A. et al. Sleep quality in the general population: psychometric properties of the Pittsburgh Sleep Quality Index, derived from a German community sample of 9284 people. Sleep Med 30, 57–63 (2017).
5. Rumanova, V. S., Okuliarova, M., Foppen, E., Kalsbeek, A. & Zeman, M. Exposure to dim light at night alters daily rhythms of glucose and lipid metabolism in rats. Front Physiol 13, (2022).
6. Rumanova, V. S., Okuliarova, M. & Zeman, M. Differential Effects of Constant Light and Dim Light at Night on the Circadian Control of Metabolism and Behavior. Int J Mol Sci 21, 1–20 (2020).
7. Daghlas, I. et al. Sleep Duration and Myocardial Infarction. J Am Coll Cardiol 74, 1304–1314 (2019).
8. Tsugane, S. Why has Japan become the world’s most long-lived country: insights from a food and nutrition perspective. European Journal of Clinical Nutrition 2020 75:6 75, 921–928 (2020).
9. Wingard, D. L. & Berkman, L. F. Mortality risk associated with sleeping patterns among adults. Sleep 6, 102–107 (1983).
10. Ikehara, S. et al. Association of sleep duration with mortality from cardiovascular disease and other causes for Japanese men and women: the JACC study. Sleep 32, 295–301 (2009).
11. Drake, C. L. et al. Effects of an experimentally induced rhinovirus cold on sleep, performance, and daytime alertness. Physiol Behav 71, 75–81 (2000).
12. Gottlieb, D. J. et al. Association of sleep time with diabetes mellitus and impaired glucose tolerance. Arch Intern Med165, 863–868 (2005).
13. Sabia, S. et al. Association of sleep duration in middle and old age with incidence of dementia. Nature Communications 2021 12:1 12, 1–10 (2021).
14. Lim, A. S. P., Kowgier, M., Yu, L., Buchman, A. S. & Bennett, D. A. Sleep Fragmentation and the Risk of Incident Alzheimer’s Disease and Cognitive Decline in Older Persons. Sleep 36, 1027–1032 (2013).
15. Li, X. et al. Gut microbiota as an “invisible organ” that modulates the function of drugs. Biomedicine & Pharmacotherapy 121, 109653 (2020).
16. Wang, Z. et al. The microbiota-gut-brain axis in sleep disorders. Sleep Med Rev 65, 101691 (2022).
17. Tarabzoni, O. et al. The Influence of Diet, Water Intake, Exercise, Education Level, and Income on the Quality of Sleep in the Saudi Population: A Cross-Sectional Study. Cureus 14, (2022).
18. Pendyala, S., Walker, J. M. & Holt, P. R. A High-Fat Diet Is Associated With Endotoxemia That Originates From the Gut. Gastroenterology 142, 1100 (2012).
19. Zhi, C. et al. Connection between gut microbiome and the development of obesity. European Journal of Clinical Microbiology & Infectious Diseases 2019 38:11 38, 1987–1998 (2019).
20. Kopp, W. How Western Diet And Lifestyle Drive The Pandemic Of Obesity And Civilization Diseases. Diabetes Metab Syndr Obes 12, 2221 (2019).
21. Yaghtin, Z., Beigrezaei, S., Yuzbashian, E., Ghayour-Mobarhan, M. & Khayyatzadeh, S. S. A greater modified Mediterranean diet score is associated with lower insomnia score among adolescent girls: a cross-sectional study. BMC Nutr 8, 1–7 (2022).
22. Wang, B., Yao, M., Lv, L., Ling, Z. & Li, L. The Human Microbiota in Health and Disease. Engineering 3, 71–82 (2017).
23. Parkin, J. & Cohen, B. An overview of the immune system. Lancet 357, 1777–1789 (2001).
24. Wright, K. P. et al. Influence of sleep deprivation and circadian misalignment on cortisol, inflammatory markers, and cytokine balance. Brain Behav Immun 47, 24–34 (2015).
25. Ishii, H. & Yoshida, M. ‘Inflammatory’ cytokines: neuromodulators in normal brain? J Neurochem 74, 819–822 (2000).
26. Krueger, J. M., Walter, J. & Dinarello, C. A. Sleep-promoting effects of endogenous pyrogen (interleukin-1). Am J Physiol 246, (1984).
27. Imeri, L. & Opp, M. R. How (and why) the immune system makes us sleep. Nat Rev Neurosci 10, 199 (2009).
28. Prather, A. A., Janicki-Deverts, D., Hall, M. H. & Cohen, S. Behaviorally Assessed Sleep and Susceptibility to the Common Cold. Sleep 38, 1353–1359 (2015).
29. K, S., JF, S. & E, V. C. Effect of sleep deprivation on response to immunization. JAMA 288, 1471-a-1472 (2002).
30. Lange, T., Perras, B., Fehm, H. L. & Born, J. Sleep enhances the human antibody response to hepatitis A vaccination. Psychosom Med 65, 831–835 (2003).
31. Wynchank, D. et al. Delayed sleep-onset and biological age: late sleep-onset is associated with shorter telomere length. Sleep 42, (2019).
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