Abstract: Sleep plays a critical role in maintaining good physical and emotional health. Sleep and circadian rhythms are fundamental regulators of human physiology, influencing most biological processes from the cellular to the organ-system level. Sleep disorders are common with a prevalence of 30% in adults. Impaired sleep reduces patients’ quality of life and has a significant negative economic impact on the health care system. Sleep deprivation can affect the brain and alter normal circadian rhythms. These disturbances influence the brain-gut axis and subsequently affect both symptom development and symptom expression in patients with disorders of gut-brain interaction (DGBIs), including functional dyspepsia and irritable bowel syndrome. DGBIs are highly prevalent with at least 40% of adults worldwide meeting criteria for at least 1 DGBI. This article reviews the prevalence and impact of disordered sleep, discusses the basics of normal and abnormal sleep, examines the role of diagnostic testing for sleep disorders, and evaluates the role of disordered sleep in common DGBIs. Practical tips to evaluate and treat patients with DGBIs and disordered sleep are also discussed.
Proper sleep is fundamental to good health and emotional well-being. Sleep, whether normal or abnormal, directly influences cardiovascular health, pulmonary and cognitive function, metabolism, the immune system, and the gastrointestinal tract.1,2 In the National Health and Nutrition Examination Survey, which included 4810 adults (ages 25-74 years) without hypertension, impaired sleep, defined as less than 5 hours per night, was associated with an increased risk of hypertension.3 The Nurses’ Health Study, which consisted of 71,617 females without coronary heart disease, found that those who slept 5 to 7 hours per night were more likely to develop coronary heart disease compared with those who slept at least 8 hours per night.4 In a case-control study of 260 men (ages 40-79 years) with and 422 men without acute myocardial infarction (matched for age and residence), sleep duration of 5 hours or less was associated with an increased risk of acute myocardial infarction, compared with sleep duration of 6 to 8 hours per night.5 These cardiovascular complications may develop, in part, owing to increased blood pressure the day following sleep deprivation
and elevated levels of norepinephrine and cortisol.6-8 Poor sleep also increases the risk of diabetes. Two separate studies involving more than 3000 adults found that sleeping 5 to 6 hours per day significantly increased the risk of developing diabetes compared with sleeping 7 to 8 hours per day.9,10 Sleep deprivation also increases the risk of obesity and metabolic syndrome.11,12 Impaired sleep negatively affects cognitive function, decision-making, and the ability to form proper memories.13 One study found that sleep deprivation and alcohol intoxication led to similar decrements in psychomotor tasks.14 Staying awake for more than 17 to 24 hours is considered equivalent to being legally drunk with a blood alcohol concentration of 0.05% to 0.10%.14 Finally, poor sleep quality increases mortality. In a prospective study of 1494 Ecuadorean adults, poor sleep quality increased the mortality risk for middle-aged and older adults by a factor of 1.38.15
Although often overlooked in clinical practice, sleep disorders affect a substantial percentage of the population. Sleep habit surveys suggest that approximately 30% of the US population sleeps less than the recommended 7-hour minimum.16 More specifically, 10% of the adult population suffers from chronic insomnia while 20% experiences symptoms of occasional insomnia.17 Key risk factors for developing a sleep disorder include age (>65 years), sex (women > men), and socioeconomic hardship.16,18 Not surprisingly, the economic costs of poor sleep are high, with one study estimating that older adults (>65 years) with insomnia had annual health care costs that were $1143 higher than those of age-matched controls without insomnia.19 The overall economic impact of insomnia in the United States (in terms of both direct and indirect costs) is estimated to be at least 100 billion US dollars per year.20 This article examines the management of disordered sleep in relation to common DGBIs.
Sleep: The Basics
The sleep cycle is not uniform; it varies from person to person. In health, the sleep cycle can be characterized as either rapid eye movement (REM) sleep or non-REM sleep. During the course of one night, the average individual goes through several rounds of the sleep cycle, which consists of 4 separate stages.21 On average, each sleep cycle lasts approximately 90 minutes, and a healthy individual will go through 4 to 6 separate sleep cycles nightly. The first full sleep cycle of the night is often the shortest, lasting anywhere from 70 to 100 minutes. The first stage of sleep (N1) occurs when an individual first falls asleep; this is the lightest stage of sleep and the time when it is easiest to awaken someone from sleep. The N1 stage of sleep may only last 1 to 7 minutes. The second stage of sleep (N2) is characterized by physiologic changes as the body starts to relax more deeply. During this stage, muscles relax, the respiratory rate and heart rate both decrease, eye movements stop, and body temperature drops. Stage 2 sleep can last for 10 to 25 minutes, although this may lengthen as the night goes on. Approximately half of the overall sleep cycle is spent in N2 sleep. The third stage of sleep, N3, is the deepest part of sleep, and it can be difficult to awaken someone during this stage. This cycle is also referred to as slow-wave sleep or delta sleep. This is thought to be the restorative stage of sleep, allowing the body to grow (in infants and adolescents) and recover from the stress of the day. This stage of sleep commonly lasts 20 to 40 minutes, although it becomes shorter as the night progresses, allowing more time to be spent in REM sleep. REM sleep is marked by heightened cortical activity, muscle atonia, vivid dreaming, and memory consolidation. Even in individuals without sleep disorders, these cycles can vary widely. For example, alcohol and caffeine negatively affect the sleep cycle by reducing both slow-wave and REM sleep early in the night. Stress, exercise, and medications can also affect the sleep cycle.18
Alterations in purinergic signaling represent a potential mechanistic link between sleep regulation and gastrointestinal function.22 In the brain, adenosine is considered the driver of the homeostatic signal, exerting modulatory effects essential for the generation of slow-wave sleep. Disruption of this homeostatic signal by adenosine receptor antagonism may contribute to sleep fragmentation and insomnia. Beyond the brain, adenosine produces systemic physiologic effects, including modulation of bradycardia. Emerging evidence suggests that adenosine may also influence gastrointestinal motility through effects on the interstitial cells of Cajal, which serve as motility pacemakers.23 Notably, caffeine, a widely consumed nonselective adenosine receptor antagonist, interferes with purinergic signaling and is a well-established contributor to insomnia. Given the prevalence of caffeine use, antagonism of adenosine signaling may represent a clinically relevant and underrecognized factor exacerbating both sleep disturbance and altered gastrointestinal function in irritable bowel syndrome (IBS).
Sleep Disorders: Diagnostic Testing
Sleep disorders can be grouped into 7 major categories: insomnia, sleep-related breathing disorders (eg, sleep apnea, snoring), central disorders of hypersomnolence (eg, narcolepsy, hypersomnia), circadian rhythm sleep-wake disorders (eg, shift-work disorder), parasomnias (eg, sleepwalking, sleep terrors), sleep-related movement disorders (eg, restless leg syndrome), and other sleep disorders.21 The diagnosis of a sleep disorder begins with a careful history. Validated screening tools such as the Insomnia Severity Index (7 items) and the STOP (Snoring, Tiredness, Observed Apnea, High Blood Pressure) questionnaire for obstructive sleep apnea (OSA) can be easily performed in the clinic.24,25 Polysomnography (PSM) is considered the gold standard for diagnosing many sleep disorders. This is performed overnight in a sleep medicine laboratory. Brain waves (electroencephalography), eye movements (electrooculography), muscle activity (electromyography), heart rate, respiratory rate, and respiratory airflow are all continuously monitored. Pulse oximetry to assess arterial oxyhemoglobin and electrocardiographic monitoring are typically performed as well. During the overnight study, patients are monitored for arousals from deep sleep to light sleep. Apnea can be detected and categorized as obstructive or central in nature. PSM can also identify hypoventilation, the presence of hypoxemia, and Cheyne-Stokes respiration. The data are interpreted in the context of the patient’s clinical status in order to provide an accurate diagnosis. However, not all patients have access to or can afford formal evaluation using PSM in a sleep medicine laboratory. Home sleep apnea testing is an alternative to PSM to help diagnose OSA, one of the most common causes of disordered sleep. Home sleep apnea testing is less costly and less invasive. This test typically measures airflow, respiratory effort, and oxygen saturation. If home sleep apnea testing is inconclusive, then PSM should be performed.26 Not surprisingly, over the past decade there has been a significant increase in the number of wearable devices to monitor sleep (wrist and finger sensors, bed-embedded sensors, audio and video recordings). At present, 9 wearable devices are approved by the US Food and Drug Administration to evaluate patients for suspected sleep apnea.27 Limited data are available from head-to-head comparisons of these devices.
The Impact of Disordered Sleep on the Brain
Sleep is restorative and vital to both mental and physical health. However, how does sleep deprivation affect the brain? There is no easy answer, in part because no single area in the brain is completely responsible for directing the sleep process. The effects of sleep deprivation can be evaluated by assessing the impact of sleep deprivation on several functional domains known to change in response to inadequate sleep. These domains include attention and task performance, memory, and emotional stability/lability, with an emphasis on anxiety. Attentional impairment and task performance are affected by impaired sleep in a dose-dependent manner; the longer the period of sleep deprivation, the greater the impact on the ability to attend to and perform tasks.28 Sleep deprivation affects the prefrontal cortex and the thalamus, areas critical to working memory.29,30 Inadequate sleep leads to significant changes in emotional instability and dysregulation, negatively impacts the ability to process and respond to emotional stimulation, and increases anxiety, an emotion controlled in part by the amygdala (Figure 1).31,32 How does sleep deprivation potentially affect patients with disorders of gut-brain interaction (DGBIs), such as functional dyspepsia (FD) and IBS? The right amygdala directly connects to the dorsal vagal complex (dorsal motor nucleus of the vagal nerve and nucleus of the solitary tract) in the lower brain stem, and thus modulates vagal nerve activity, a key driver of gastrointestinal function.33 The thalamus plays a critical role in visceral sensory signaling, whereas the prefrontal cortex is involved in parasympathetic signaling, pain, and emotions. Sleep deprivation thus has the potential to dramatically affect the brain-gut axis, the bidirectional highway intimately involved in the development of DGBIs such as FD and IBS.
Sleep Disorders and Functional Dyspepsia
FD is among the most common DGBIs with a pooled global prevalence of 8.4%, and a prevalence of 7.2% using Rome IV criteria.34-36 FD is characterized by bothersome epigastric pain, burning, early satiation, and/or postprandial fullness, which may be accompanied by nausea or vomiting per the Rome V criteria.37 The condition can be further subdivided into epigastric pain syndrome, where pain is the predominant symptom, or postprandial distress syndrome. A survey of 171 patients found that 70% of those with FD (Rome III criteria) reported sleep disturbances, and those with more severe dyspeptic symptoms reported worse sleep disturbances.38 Similarly, a prospective study by Huang and colleagues found that sleep disturbances were more common in patients with FD (n=145; Rome IV criteria) compared with controls (n=273), and symptoms were correlated with dyspepsia severity.39 In a cross-sectional multicenter study of 526 patients, those with FD (n=201; Rome III criteria) had a higher prevalence of sleep disorders than healthy controls (n=325), and a multivariate analysis identified female sex, lower body mass index, and anxiety as additional risk factors for sleep disorders.40 There is a significant association between reduced quality of life and both altered sleep quality and insomnia in patients with FD (Rome IV criteria).41 It is debated whether FD symptoms are the cause or result of sleep disturbances; however, a prospective study of 16 patients with FD who were prescribed sleep aids found that improved sleep disturbances led to improvement in gastrointestinal symptoms and quality of life.42 Although the evidence supports a bidirectional relationship between sleep and gastrointestinal disorders (FD in particular), the underlying mechanism remains poorly elucidated. Gastrointestinal inflammation likely plays a role as seen in a randomized controlled trial where treatment of sleep disturbances in FD led to reduced epigastric pain and serum inflammatory markers.43 Another study linked reduced melatonin synthesis to epigastric pain in epigastric pain syndrome, one of the two subtypes of FD (Rome III criteria).44 Several studies have demonstrated success of nonpharmacologic treatments in managing insomnia in patients with FD, including mindfulness-based cognitive therapy, exercise, auricular acupressure, and digestive enzyme supplementation.45-48 With respect to potential pharmacologic approaches, nizatidine 300 mg daily showed promise in improving gastroesophageal reflux, gastric emptying, and impaired sleep in patients with FD when compared with placebo in a 4-week crossover trial.49
Sleep Disorders and Irritable Bowel Syndrome
IBS is another of the most common DGBIs with a pooled global prevalence of 4% to 9% in the general population.50 According to the Rome V criteria, IBS is characterized by abdominal pain and altered bowel habits.51 Although a number of treatment options are available to treat these IBS symptoms, guidelines do not routinely discuss the treatment of comorbid sleep disorders.52,53 Impaired sleep is more common in patients with IBS compared with healthy controls with a pooled prevalence of 38%.54 A case-control study of 200 patients (age 15 years and older) referred to a sleep laboratory found that those diagnosed with sleep apnea were nearly 4 times more likely to report symptoms of IBS.55 In a study of women with IBS (mean age 32 years; Rome II criteria), insomnia was associated with a worsening of abdominal pain, anxiety, and fatigue the following day; however, poor sleep was not associated with a change in bowel habits.56 Although the sample size of this study is modest, the finding that abdominal pain is worsened the day after a poor night’s sleep is worth emphasizing in a holistic treatment plan, as discussed in the following sections. In a prospective study comparing patients with IBS (n=24; Rome III criteria) with healthy controls (n=26), patients with IBS were found to sleep more but have more waking episodes and were less well-rested than healthy controls.57 Interestingly, in both of these studies, patients with IBS did not feel that their abdominal pain was the cause of their disrupted sleep. However, an increased number of waking episodes was associated with a worsening of abdominal pain while overall impaired sleep predicted an increased number of days with symptoms of abdominal pain and gastrointestinal distress. These findings highlight the need to address disordered sleep, which should then improve abdominal pain. Similar to the study by Buchanan and colleagues, impaired sleep was not associated with a worsening of bowel habits.56 Disrupted sleep owing to shift work may contribute to a worsening of abdominal pain, as demonstrated in a study of nurses working rotating shifts compared with colleagues working fixed schedules.58 Although patients with IBS likely have a variety of causes responsible for impaired sleep, one of the few studies using an objective measure of sleep (PSM) found that patients with IBS experience shallow, nonrestorative sleep.59 Few studies have focused specifically on treating sleep disorders in patients with IBS. An analysis of 4 placebo-controlled trials evaluating melatonin in patients with IBS found that a daily dose (3 mg; 2-24 weeks) was more likely to improve abdominal pain and other global symptoms than placebo.60
Sleep Disorders and Other Disorders of Gut-Brain Interaction
Data evaluating the role of sleep and other DGBIs are lacking; however, sleep appears to play a role in gastrointestinal conditions in general such as gastroesophageal reflux. Studies have demonstrated a bidirectional relationship between gastroesophageal reflux and sleep. A survey of 11,685 patients with gastroesophageal reflux found that those with nighttime gastroesophageal reflux symptoms were more likely to experience sleep difficulties.61 Sleep deficiency, defined as 2 nights of only 4 hours of sleep, was associated with an increase in esophageal acid exposure in a randomized controlled trial comparing healthy patients and those with gastroesophageal reflux.62 In another randomized controlled trial, patients with gastroesophageal reflux were more likely to report symptoms after sleep deprivation compared with healthy controls who experienced sleep deprivation.63 These data are not surprising and raise the question of whether evaluation for sleep disorders should play a standard role in the evaluation of any patients with gastrointestinal symptoms.
Evaluating and Treating Sleep Disorders in Patients With Disorders of Gut-Brain Interaction
Insomnia is the most common sleep disorder in adults. The high prevalence of insomnia and the impact of disrupted sleep on the brain-gut axis highlight the need to ask all patients with DGBIs about their sleep. Patients should be asked the following questions about sleep over the past month: Do you have trouble staying asleep? Do you wake up early or too often? Are you satisfied with your sleep? Does poor sleep interfere with your ability to function? Are your sleep issues noticeable by others? Finally, are you worried about your sleep? These questions, modified from the Insomnia Severity Index, have high discriminative ability to identify insomnia and can be easily incorporated into a standard review of systems.24 If 2 or 3 of these questions are answered affirmatively with moderate-high frequency, then it is worth addressing impaired sleep in the overall treatment plan. This is critical because improving sleep may enhance emotional stability, anxiety, memory, and coping skills and thus improve global DGBI symptoms. Treating disordered sleep should begin with sleep hygiene basics (Table and Figure 2). If insomnia persists despite following sleep hygiene recommendations, then referral to a sleep medicine specialist should be considered. Alternatively, if there is no suspicion of additional sleep apnea, sleep aids can be employed.
Based on a systematic review of the literature, cognitive behavioral therapy for insomnia (CBT-I) is considered first-line therapy with demonstrated efficacy in improving sleep continuity, reducing hyperarousal, and indirectly alleviating gastrointestinal symptoms.64 Pharmacologic interventions, reviewed later in this section, should be used cautiously, favoring agents with minimal cognitive side effects.
Circadian misalignment, including delayed sleep-wake phase, shift work, and irregular sleep timing, may further exacerbate gastrointestinal symptoms by disrupting gastrointestinal motility, intestinal permeability, and microbial rhythmicity. Treatment strategies focus on circadian realignment through structured sleep-wake schedules, timed light exposure, and appropriately scheduled melatonin administration. Exogenous melatonin has shown promise in IBS by improving sleep quality and exerting motility-regulating effects on the gastrointestinal tract.65 Chronotherapy and behavioral interventions aimed at stabilizing circadian rhythms may improve both sleep efficiency and daytime gastrointestinal function, although data from large randomized controlled trials in patients with DGBIs are lacking.
Melatonin is a chronobiotic that may improve the normal circadian rhythm of sleep, and it may help patients with jet lag and occasional insomnia; benefits for patients with changing shift-work schedules are marginal.65 As noted previously, melatonin may improve symptoms in patients with IBS; data from randomized controlled trials in patients with FD are not available. It generally works best if taken 1 to 2 hours before the desired sleep time. Lower doses (1-3 mg) are typically all that are required for circadian resynchronization; long-acting formulations are also available. Morning drowsiness and headaches are the most common reported side effects. In more severe insomnia cases, prescription medications may be
necessary.
Multiple medications, including both benzodiazepines and nonbenzodiazepines, are available to treat sleep disorders.66 Dual orexin receptor antagonists such as suvorexant inhibit the wake-promoting neurotransmitter orexin and may prove useful if conservative measures fail (Figure 2). Prospective studies of these agents in patients with DGBIs have not been performed. Because of the potential for side effects with all of these agents, and owing to risks of hypnotic dependency, therapeutic trials should begin with the lowest dose possible, and patients should be carefully monitored. Typical side effects of prescription sleep aids include excess somnolence the following day, impaired coordination, unusual dreams, zolpidem-induced sleepwalking, dizziness, headaches, dry mouth, memory loss, agitation, and gastrointestinal side effects, including constipation and diarrhea.
OSA is increasingly recognized in patients with IBS. Intermittent hypoxia and sleep fragmentation in OSA contribute to systemic inflammation and heightened pain sensitivity, potentially worsening IBS symptoms. Positive airway pressure therapy remains the cornerstone of OSA management and has been associated with improvements in sleep quality, daytime fatigue, and inflammatory markers. In a patient with a DGBI and documented OSA, this is a logical first treatment, recognizing that although CBT-I is quite effective, it can be difficult to identify a well-trained therapist to perform CBT-I. Additional therapeutic approaches include hypoglossal nerve stimulation and tirzepatide, a dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist, for the treatment of sleep apnea in patients with obesity.67 The precise positioning of these agents in a treatment cascade is difficult to establish, as data from large prospective studies in patients with DGBIs do not exist and head-to- head comparison studies of these agents in patients with sleep disorders are lacking. Optimizing OSA treatment may provide secondary benefits on gastrointestinal symptoms and overall quality of life in IBS patients.
Symptoms of psychological distress (eg, anxiety and depression) are more prevalent in patients with IBS and FD than in the general population.68 Stress is both a causative factor and exacerbating factor for many patients with DGBI symptoms.69,70 In addition, many patients with IBS, especially those with diarrhea, become hypervigilant about their symptoms and focus on the possibility that their symptoms will worsen at inopportune times (eg, social or work activities). These points are worth mentioning because all of these conditions are also commonly associated with poor sleep. This emphasizes the need for a holistic treatment approach for patients with DGBIs, psychological distress, and poor sleep. As noted previously, this may include lifestyle and medical therapy for DGBI symptoms, treatment for ongoing psychological distress (which may include brain-gut behavioral therapy), and treatment for disordered sleep using CBT-I or medical therapy.
Summary
Proper sleep is vital to overall health. It is recommended that adults (ages 18-65 years) sleep 7 to 9 hours/day while those over the age of 65 years sleep 7 to 8 hours/day. Sleep deprivation has myriad negative effects, including emotional lability, decreased attention, impaired memory, compromised task performance, and increased anxiety. Sleep deprivation affects key areas of the brain involved in the brain-gut axis, thus potentially influencing gastrointestinal symptoms in patients with DGBIs. Asking about sleep disorders in patients with DGBIs is critical and should be a part of a standard review of systems. The treatment of sleep disorders in patients with IBS and other DGBIs includes an interdisciplinary approach targeting insomnia, circadian misalignment, and sleep apnea. Behavioral therapies, circadian-based interventions, and targeted pharmacologic or device-based treatments should be individualized. Addressing sleep disorders represents a modifiable therapeutic pathway, with the potential to improve both sleep and gastrointestinal outcomes in patients with DGBIs.
Disclosures
The authors have no relevant conflicts of interest to disclose.
References
1. Shah AS, Pant MR, Bommasamudram T, et al. Effects of sleep deprivation on physical and mental health outcomes: an umbrella review. Am J Lifestyle Med. 2025;27:15598276251346752.
2. Nagai M, Hoshide S, Kario K. Sleep duration as a risk factor for cardiovascular disease—a review of the recent literature. Curr Cardiol Rev. 2010;6(1):54-61.
3. Gangwisch JE, Heymsfield SB, Boden-Albala B, et al. Short sleep duration as a risk factor for hypertension: analyses of the first National Health and Nutrition Examination Survey. Hypertension. 2006;47(5):833-839.
4. Ayas NT, White DP, Manson JE, et al. A prospective study of sleep duration and coronary heart disease in women. Arch Intern Med. 2003;163(2):205-209.
5. Liu Y, Tanaka H; Fukuoka Heart Study Group. Overtime work, insufficient sleep, and risk of non-fatal acute myocardial infarction in Japanese men. Occup Environ Med. 2002;59(7):447-451.
6. Lusardi P, Mugellini A, Preti P, Zoppi A, Derosa G, Fogari R. Effects of a restricted sleep regimen on ambulatory blood pressure monitoring in normotensive subjects. Am J Hypertens. 1996;9(5):503-505.
7. Tochikubo O, Ikeda A, Miyajima E, Ishii M. Effects of insufficient sleep on blood pressure monitored by a new multibiomedical recorder. Hypertension. 1996;27(6):1318-1324.
8. Irwin MR, Ziegler M. Sleep deprivation potentiates activation of cardiovascular and catecholamine responses in abstinent alcoholics. Hypertension. 2005;45(2):252-257.
9. Gottlieb DJ, Punjabi NM, Newman AB, et al. Association of sleep time with diabetes mellitus and impaired glucose tolerance. Arch Intern Med. 2005;165(8):863-867.
10. Yaggi HK, Araujo AB, McKinlay JB. Sleep duration as a risk factor for the development of type 2 diabetes. Diabetes Care. 2006;29(3):657-661.
11. Wu Y, Zhai L, Zhang D. Sleep duration and obesity among adults: a meta-analysis of prospective studies. Sleep Med. 2014;15(12):1456-1462.
12. Xi B, He D, Zhang M, Xue J, Zhou D. Short sleep duration predicts risk of metabolic syndrome: a systematic review and meta-analysis. Sleep Med Rev. 2014;18(4):293-297.
13. Khan MA, Al-Jahdali H. The consequences of sleep deprivation on cognitive performance. Neurosciences (Riyadh). 2023;28(2):91-99.
14. Elmenhorst EM, Elmenhorst D, Benderoth S, Kroll T, Bauer A, Aeschbach D. Cognitive impairments by alcohol and sleep deprivation indicate trait characteristics and a potential role for adenosine A1 receptors. Proc Natl Acad Sci USA. 2018;115(31):8009-8014.
15. Del Brutto OH, Mera RM, Rumbea DA, Sedler MJ, Castillo PR. Poor sleep quality increases mortality risk: a population-based longitudinal prospective study in community-dwelling middle-aged and older adults. Sleep Health. 2024;10(1):144-148.
16. Liu Y, Wheaton AG, Chapman DP, Cunningham TJ, Lu H, Croft JB. Prevalence of healthy sleep duration among adults—United States, 2014. MMWR Morb Mortal Wkly Rep. 2016;65(6):137-141.
17. Madan Jha V. The prevalence of sleep loss and sleep disorders in young and old adults. Aging Brain. 2022;3:100057.
18. Morin CM, Jarrin DC. Epidemiology of insomnia: prevalence, course, risk factors, and public health burden. Sleep Med Clin. 2022;17(2):173-191.
19. Ozminkowski RJ, Wang S, Walsh JK. The direct and indirect costs of untreated insomnia in adults in the United States. Sleep. 2007;30(3):263-273.
20. Wickwire EM, Tom SE, Scharf SM, Vadlamani A, Bulatao IG, Albrecht JS. Untreated insomnia increases all-cause health care utilization and costs among Medicare beneficiaries. Sleep. 2019;42(4):zsz007.
21. Berry RB, Brooks R, Gamaldo C, et al. AASM scoring manual updates for 2017 (version 2.4). J Clin Sleep Med. 2017;13(5):665-666.
22. Castillo PR. Clinical neurobiology of sleep and wakefulness. Continuum (Minneap Minn). 2023;29(4):1016-1030.
23. Choi S, Lee JH, Shin DH, et al. Effect of adenosine-1 receptor activation on pacemaker activity of interstitial cells of Cajal from mouse colon. Cell Mol Biol (Noisy-le-Grand). 2023;69(2):67-73.
24. Morin CM, Belleville G, Bélanger L, Ivers H. The Insomnia Severity Index: psychometric indicators to detect insomnia cases and evaluate treatment response. Sleep. 2011;34(5):601-608.
25. Patel D, Tsang J, Saripella A, et al. Validation of the STOP questionnaire as a screening tool for OSA among different populations: a systematic review and meta-regression analysis. J Clin Sleep Med. 2022;18(5):1441-1453.
26. Sim MJH, Poh Y, Wong HS, Mok Y. Failure to complete diagnostic testing in patients with suspected obstructive sleep apnoea and inconclusive home sleep apnoea test. Sleep Breath. 2025;29(5):277.
27. Chiang AA, Jerkins E, Holfinger S, et al. OSA diagnosis goes wearable: are the latest devices ready to shine? J Clin Sleep Med. 2024;20(11):1823-1838.
28. Belenky G, Wesensten NJ, Thorne DR, et al. Patterns of performance degradation and restoration during sleep restriction and subsequent recovery: a sleep dose-response study. J Sleep Res. 2003;12(1):1-12.
29. Chee MW, Choo WC. Functional imaging of working memory after 24 hr of total sleep deprivation. J Neurosci. 2004;24(19):4560-4567.
30. Ma N, Dinges DF, Basner M, Rao H. How acute total sleep loss affects the attending brain: a meta-analysis of neuroimaging studies. Sleep. 2015;38(2):233-240.
31. Palmer CA, Bower JL, Cho KW, et al. Sleep loss and emotion: a systematic review and meta-analysis of over 50 years of experimental research. Psychol Bull. 2024;150(4):440-463.
32. Pires GN, Bezerra AG, Tufik S, Andersen ML. Effects of acute sleep deprivation on state anxiety levels: a systematic review and meta-analysis. Sleep Med. 2016;24:109-118.
33. Reimann GM, Hoseini A, Koçak M, et al. Distinct convergent brain alterations in sleep disorders and sleep deprivation: a meta-analysis. JAMA Psychiatry. 2025;82(7):681-691.
34. Sperber AD, Bangdiwala SI, Drossman DA, et al. Worldwide prevalence and burden of functional gastrointestinal disorders, results of Rome Foundation Global Study. Gastroenterology. 2021;160(1):99-114.e3.
35. Lee K, Kwon CI, Yeniova AÖ, et al. Global prevalence of functional dyspepsia according to Rome criteria, 1990-2020: a systematic review and meta-analysis. Sci Rep. 2024;14(1):4172.
36. Tack J, Palsson OS, Bangdiwala SI, et al. Functional dyspepsia and its subgroups: prevalence and impact in the Rome IV Global Epidemiology Study. Aliment Pharmacol Ther. 2025;62(3):330-339.
37. Törnblom H, Carbone F, Hasler WL, et al. Gastroduodenal disorders. Gastroenterology. 2026;170(6):1240-1260.
38. Lacy BE, Everhart K, Crowell MD. Functional dyspepsia is associated with sleep disorders. Clin Gastroenterol Hepatol. 2011;9(5):410-414.
39. Huang ZP, Li SM, Shen T, Zhang YY. Correlation between sleep impairment and functional dyspepsia. J Int Med Res. 2020;48(7):300060520937164.
40. Park JK, Huh KC, Kwon JG, et al. Sleep disorders in patients with functional dyspepsia: a multicenter study from the Korean Society of Neurogastroenterology and Motility. J Gastroenterol Hepatol. 2021;36(3):687-693.
41. Wuestenberghs F, Melchior C, Desprez C, Leroi AM, Netchitailo M, Gourcerol G. Sleep quality and insomnia are associated with quality of life in functional dyspepsia. Front Neurosci. 2022;16:829916.
42. Nakamura F, Kuribayashi S, Tanaka F, et al. Impact of improvement of sleep disturbance on symptoms and quality of life in patients with functional dyspepsia. BMC Gastroenterol. 2021;21(1):78.
43. Du H, Lin R, Xiao S, et al. Improved sleep affects epigastric pain in functional dyspepsia by reducing the levels of inflammatory mediators. Dig Dis. 2023;41(6):835-844.
44. Chojnacki C, Poplawski T, Blasiak J, Chojnacki J, Klupinska G. Does melatonin homeostasis play a role in continuous epigastric pain syndrome? Int J Mol Sci. 2013;14(6):12550-12562.
45. Long X, Liying W, Zhuoran L, et al. The effect of mindfulness-based cognitive therapy on the clinical efficacy and psychological state in patients with functional dyspepsia. Scand J Gastroenterol. 2024;59(8):900-905.
46. Huang Z, Zhuang Y, Lin T, Liu S, Wu J. Efficacy of exercise therapies on functional dyspepsia: a systematic review and meta-analysis. Dig Liver Dis. 2025;57(11):2087-2098.
47. Shen MY, Li ZJ, Zhou R, et al. Efficacy and safety of auricular acupressure for insomnia in patients with functional dyspepsia: a randomized controlled trial [published online December 10, 2025]. Am J Gastroenterol. doi:10.14309/ajg.0000000000003880.
48. Ullah H, Di Minno A, Piccinocchi R, et al. Efficacy of digestive enzyme supplementation in functional dyspepsia: a monocentric, randomized, double-blind, placebo-controlled, clinical trial. Biomed Pharmacother. 2023;169:115858.
49. Futagami S, Yamawaki H, Izumi N, et al. Impact of sleep disorders in Japanese patients with functional dyspepsia (FD): nizatidine improves clinical symptoms, gastric emptying and sleep disorders in FD patients. J Gastroenterol Hepatol. 2013;28(8):1314-1320.
50. Oka P, Parr H, Barberio B, Black CJ, Savarino EV, Ford AC. Global prevalence of irritable bowel syndrome according to Rome III or IV criteria: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2020;5(10):908-917.
51. Corsetti M, Shin A, Lacy BE, et al. Bowel disorders. Gastroenterology. 2026;170(6):1261-1282.
52. Lacy BE, Pimentel M, Brenner DM, et al. ACG clinical guideline: management of irritable bowel syndrome. Am J Gastroenterol. 2021;116(1):17-44.
53. Ford AC, Lacy BE, Talley NJ. Irritable bowel syndrome. N Engl J Med. 2017;376(26):2566-2578.
54. Wang B, Duan R, Duan L. Prevalence of sleep disorder in irritable bowel syndrome: a systematic review with meta-analysis. Saudi J Gastroenterol. 2018;24(3):141-150.
55. Ghiasi F, Amra B, Sebghatollahi V, Azimian F. Association of irritable bowel syndrome and sleep apnea in patients referred to sleep laboratory. J Res Med Sci. 2017;22:72.
56. Buchanan DT, Cain K, Heitkemper M, et al. Sleep measures predict next-day symptoms in women with irritable bowel syndrome. J Clin Sleep Med. 2014;10(9):1003-1009.
57. Patel A, Hasak S, Cassell B, et al. Effects of disturbed sleep on gastrointestinal and somatic pain symptoms in irritable bowel syndrome. Aliment Pharmacol Ther. 2016;44(3):246-258.
58. Nojkov B, Rubenstein JH, Chey WD, Hoogerwerf WA. The impact of rotating shift work on the prevalence of irritable bowel syndrome in nurses. Am J Gastroenterol. 2010;105(4):842-847.
59. Rotem AY, Sperber AD, Krugliak P, Freidman B, Tal A, Tarasiuk A. Polysomnographic and actigraphic evidence of sleep fragmentation in patients with irritable bowel syndrome. Sleep. 2003;26(6):747-752.
60. Siah KT, Wong RK, Ho KY. Melatonin for the treatment of irritable bowel syndrome. World J Gastroenterol. 2014;20(10):2492-2498.
61. Mody R, Bolge SC, Kannan H, Fass R. Effects of gastroesophageal reflux disease on sleep and outcomes. Clin Gastroenterol Hepatol. 2009;7(9):953-959.
62. Yamasaki T, Quan SF, Fass R. The effect of sleep deficiency on esophageal acid exposure of healthy controls and patients with gastroesophageal reflux disease. Neurogastroenterol Motil. 2019;31(12):e13705.
63. Schey R, Dickman R, Parthasarathy S, et al. Sleep deprivation is hyperalgesic in patients with gastroesophageal reflux disease. Gastroenterology. 2007;133(6):1787-1795.
64. Melo DLM, Carvalho LBC, Prado LBF, Prado GF. Biofeedback therapies for chronic insomnia: a systematic review. Appl Psychophysiol Biofeedback. 2019;44(4):259-269.
65. Costello RB, Lentino CV, Boyd CC, et al. The effectiveness of melatonin for promoting healthy sleep: a rapid evidence assessment of the literature. Nutr J. 2014;13:106.
66. De Crescenzo F, D’Alò GL, Ostinelli EG, et al. Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis. Lancet. 2022;400(10347):170-184.
67. US Food and Drug Administration. FDA approves first medication for obstructive sleep apnea. https://www.fda.gov/news-events/press-announcements/fda-approves-first-medication-obstructive-sleep-apnea. Published December 20, 2024. Accessed June 2026.
68. Zamani M, Alizadeh-Tabari S, Zamani V. Systematic review with meta-analysis: the prevalence of anxiety and depression in patients with irritable bowel syndrome. Aliment Pharmacol Ther. 2019;50(2):132-143.
69. Qin HY, Cheng CW, Tang XD, Bian ZX. Impact of psychological stress on irritable bowel syndrome. World J Gastroenterol. 2014;20(39):14126-14131.
70. Elsenbruch S, Rosenberger C, Bingel U, Forsting M, Schedlowski M, Gizewski ER. Patients with irritable bowel syndrome have altered emotional modulation of neural responses to visceral stimuli. Gastroenterology. 2010;139(4):1310-1319.