From the Perspective of TCM Theory of “Vigorous in Day and Sleeping Well at Night”: The Interactive Influence Between Insomnia and Digestive System Diseases

Kongxi Zhu, Shan Qin

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¹ Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210000, Jiangsu, China,

CNR 2026 , 4(1), 26–38; https://doi.org/10.26689/cnr.v4i1.14291

© 2026 by the Authors. Licensee Whioce Publishing, Singapore. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )

Abstract

For a long time, insufficient attention has been paid to the complex relationship between insomnia and digestive system diseases. Studies have found that “vigorous in day and sleeping well at night” plays an important regulatory role in both. The imbalance of arousal-sleep rhythm can lead to various forms of insomnia and digestive system diseases, which may also be one of the keys to the bidirectional influence between insomnia and digestive system diseases. Therefore, this paper will sort out the relationship between insomnia and digestive system diseases based on this characteristic, in order to provide a basis for clinical treatment.

References

Kanaly T, Shaheen, NJ, Vaughn BV, 2009, Gastrointestinal Physiology and Digestive Disorders in Sleep. Current Opinion in Pulmonary Medicine, 2009(15): 571–577. https://doi.org/10.1097/MCP.0b013e3283318539

Fass R, Fullerton S, Tung S, et al., 2000, Sleep Disturbances in Clinic Patients with Functional Bowel Disorders. The American Journal of Gastroenterology, 2000(95): 1195–2000. https://doi.org/10.1111/j.1572-0241.2000.02009.x

Zhang NQ, Feng YM, 2022, Yellow Emperor’s Inner Canon. Hubei Science and Technology Press: Hubei, 590.

Albrecht U, 2012, Timing to Perfection: The Biology of Central and Peripheral Circadian Clocks. Neuron, 2012(74): 246–260. https://doi.org/10.1016/j.neuron.2012.04.006

Wang D, Yin H, Wang X, et al., 2022, Influence of Sleep Disruption on Inflammatory Bowel Disease and Changes in Circadian Rhythm Genes. Heliyon, 2022(8): e11229. https://doi.org/10.1016/j.heliyon.2022.e11229

Liu X, Yu R, Zhu L, et al., 2017, Bidirectional Regulation of Circadian Disturbance and Inflammation in Inflammatory Bowel Disease. Inflammatory Bowel Disease, 2017(23): 1741–1751. https://doi.org/10.1097/mib.0000000000001265

Lear CS, Flanagan JB Jr., Moorrees CF, 1965, The Frequency of Deglutition in Man. Archives of Oral Biology, 1965(10): 83–100. https://doi.org/10.1016/0003-9969(65)90060-9

Castiglione, Emde FC, Armstrong D, et al., 1993, Nocturnal Oesophageal Motor Activity is Dependent on Sleep Stage. Gut, 1993(34): 1653–1659 (1993). https://doi.org/10.1136/gut.34.12.1653

Furukawa Y, Cook IJ, Panagopoulos V, et al., 1994, Relationship between Sleep Patterns and Human Colonic Motor Patterns. Gastroenterology, 1994(107): 1372–1381. https://doi.org/10.1016/0016-5085(94)90539-8

Schneyer LH, Pigman W, Hanahan L, et al., 1956, Rate of Flow of Human Parotid, Sublingual, and Submaxillary Secretions during Sleep. Journal of Dental Research, 1956(35): 109–114. https://doi.org/10.1177/00220345560350010301

Watanabe M. Nakazawa S, Yoshino J, et al., 1995, A Study of the Relationship between Nocturnal Intragastric pH and Sleep Stages of Peptic Ulcer. Nihon Shokakibyo Gakkai Zasshi, 1995(92): 1241–1249.

Hoogerwerf WA, 2009, Role of Biological Rhythms in Gastrointestinal Health and Disease. Reviews in Endocrine and Metabolic Disorders, 2009(10): 293–300. https://doi.org/10.1007/s11154-009-9119-3

Crosby P, Hamnett R, Putkeret M, et al., 2019, Insulin/IGF-1 Drives PERIOD Synthesis to Entrain Circadian Rhythms with Feeding Time. Cell, 2019(177): 909.e820. https://doi.org/10.1016/j.cell.2019.02.017

Zheng L, Seon YJ, McHugh J, et al., 2012, Clock Genes Show Circadian Rhythms in Salivary Glands. Journal of Dental Research, 2012(91): 788. https://doi.org/10.1177/0022034512451450

Furukawa M, Kawamoto T, Noshiro M, et al., 2005, Clock Gene Expression in the Submandibular Glands. Journal of Dental Research, 2005(84): 1193–1197. https://doi.org/10.1177/154405910508401219

Hoogerwerf WA, Hellmich HL, Cornélissen G, et al., 2007, Clock Gene Expression in the Murine Gastrointestinal Tract: Endogenous Rhythmicity and Effects of a Feeding Regimen. Gastroenterology, 2007(133): 1250–1260. https://doi.org/10.1053/j.gastro.2007.07.009

Auwerda JJ, Bac DJ, Schouten WR, 2001, Circadian Rhythm of Rectal Motor Complexes. Diseases of the Colon & Rectum, 2001(44): 1328–1332. https://doi.org/10.1007/bf02234793

Palmieri O, Mazzoccoli G, Bossa F, et al., 2015, Systematic Analysis of Circadian Genes using Genome-wide cDNA Microarrays in the Inflammatory Bowel Disease Transcriptome. Chronobiology International, 2015(32): 903–916. https://doi.org/10.3109/07420528.2015.1050726

Mazzoccoli G, De Cata A, Greco A, et al., 2010, Circadian Rhythmicity of Lymphocyte Subpopulations and Relationship with Neuro-endocrine System. Journal of Biological Regulators and Homeostatic Agents, 2010(24): 341–350.

Ma Y, Yu S, Li Q, et al., 2024, Sleep Patterns, Genetic Susceptibility, and Digestive Diseases: A Large-scale Longitudinal Cohort Study. International Surgery Journal, 2024(110): 5471–5482. https://doi.org/10.1097/js9.0000000000001695

Marinelli C, Savarino EV, Marsilio I, et al., 2020, Sleep Disturbance in Inflammatory Bowel Disease: Prevalence and Risk Factors — A Cross-sectional Study. Science Reports, 2020(10): 507. https://doi.org/10.1038/s41598-020-57460-6

Sobolewska-Włodarczyk A, Włodarczyk M, Talar M, et al., 2021, The Association of the Quality of Sleep with Proinflammatory Cytokine Profile in Inflammatory Bowel Disease Patients. Pharmacological Reports, 2021(73): 1660–1669. https://doi.org/10.1007/s43440-021-00333-0

Ali T, Madhoun MF, Orr WC, et al., 2013, Assessment of the Relationship between Quality of Sleep and Disease Activity in Inflammatory Bowel Disease Patients. Inflammatory Bowel Diseases, 2013(19): 2440–2443. https://doi.org/10.1097/MIB.0b013e3182a0ea54

Cavadini G, Petrzilka S, Kohler P, et al., 2007, TNF-alpha Suppresses the Expression of Clock Genes by Interfering with E-box-mediated Transcription. Proceedings of the National Academy of Sciences of the United States of America, 2007(104): 12843–12848. https://doi.org/10.1073/pnas.0701466104

Tang Y, Preuss F, Turek FW, et al., 2009, Sleep Deprivation Worsens Inflammation and Delays Recovery in a Mouse Model of Colitis. Sleep Medicine, 2009(10): 597–603. https://doi.org/10.1016/j.sleep.2008.12.009

Li ZQ, Miao YL, 2022, The Bidirectional Relationship Between Inflammatory Bowel Disease and Insomnia. Gastroenterology, 2022(27): 637–640.

Codoñer-Franch P, Gombert M, 2018, Circadian Rhythms in the Pathogenesis of Gastrointestinal Diseases. Journal of Gastroenterology and Hepatology, 2018(24): 4297–4303. https://doi.org/10.3748/wjg.v24.i38.4297

Vege SS, Locke GR 3rd, Weaver AL, et al., 2004, Functional Gastrointestinal Disorders among People with Sleep Disturbances: A Population-based Study. Mayo Clinic Proceedings, 2004(79): 1501–1506. https://doi.org/10.4065/79.12.1501

Chen CL, Liu TT, Yi CH, et al., 2011, Evidence for Altered Anorectal Function in Irritable Bowel Syndrome Patients with Sleep Disturbance. Digestion, 2011(84): 247–251. https://doi.org/10.1159/000330847

Axelsson J, Rehman JU, Akerstedt T, et al., 2013, Effects of Sustained Sleep Restriction on Mitogen-stimulated Cytokines, Chemokines and T Helper 1/ T Helper 2 Balance in Humans. PLoS One, 2013(8): e82291. https://doi.org/10.1371/journal.pone.0082291

Malhotra S, Sawhney G, Pandhi P, 2004, The Therapeutic Potential of Melatonin: a Review of the Science. MedGenMed, 2004(6): 46.

Orr WC, Fass R, Sundaram SS, et al., 2020, The Effect of Sleep on Gastrointestinal Functioning in Common Digestive Diseases. The Lancet Gastroenterology & Hepatology, 2020(5): 616–624. https://doi.org/10.1016/s2468-1253(19)30412-1

Orr WC, Johnson LF, Robinson MG, 1984, Effect of Sleep on Swallowing, Esophageal Peristalsis, and Acid Clearance. Gastroenterology, 1984(86): 814–819.

Orr WC, Elsenbruch S, Harnish MJ, et al., 2000, Proximal Migration of Esophageal Acid Perfusions during Waking and Sleep. The American Journal of Gastroenterology, 2000(95): 37–42. https://doi.org/10.1111/j.1572-0241.2000.01669.x

Frazzoni M, De Micheli E, Savarino V, 2003, Different Patterns of Oesophageal Acid Exposure Distinguish Complicated Reflux Disease from either Erosive Reflux Oesophagitis or Non-erosive Reflux Disease. Alimentary Pharmacology & Therapeutics, 2003(18): 1091–1098. https://doi.org/10.1046/j.1365-2036.2003.01768.x

Nakahara K, Fujiwara Y, Tsukahara T, et al., 2014, Acid Reflux Directly Causes Sleep Disturbances in Rat with Chronic Esophagitis. PLoS One, 2014(9): e106969. https://doi.org/10.1371/journal.pone.0106969

Fass R, 2009, The Relationship between Gastroesophageal Reflux Disease and Sleep. Current Gastroenterology Reports, 2009(11): 202–208. https://doi.org/10.1007/s11894-009-0032-4

Hashimoto A, Uemura R, Sawada A, et al., 2019, Changes in Clock Genes Expression in Esophagus in Rat Reflux Esophagitis. Digestive Diseases and Sciences, 2019(64): 2132–2139. https://doi.org/10.1007/s10620-019-05546-1

Dickman R, Green C, Fass SS, et al., 2007, Relationships between Sleep Quality and pH Monitoring Findings in Persons with Gastroesophageal Reflux Disease. Journal of Clinical Sleep Medicine, 2007(3): 505–513.

Malfertheiner P, Chan FK, McColl KE, 2009, Peptic Ulcer Disease. Lancet, 2009(374): 1449–1461. https://doi.org/10.1016/s0140-6736(09)60938-7

Lanas A, Chan FKL, 2017, Peptic Ulcer Disease. Lancet, 2017(390): 613–624. https://doi.org/10.1016/s0140-6736(16)32404-7

Fang B, Yang S, Xu R, et al., 2019, Association between Poor Sleep Quality and Subsequent Peptic Ulcer Recurrence in Older Patients with Mild Cognitive Impairment: Examining the Role of Social Engagement. Scientific Reports, 2019(9): 2188.

Ko SH, Baeg MK, Ko SY, et al., 2016, Women Who Sleep More Have Reduced Risk of Peptic Ulcer Disease; Korean National Health and Nutrition Examination Survey (2008–2009). Science Reports, 2016(6): 36925. https://doi.org/10.1038/srep36925

Zha LF, Dong JT, Wang JL, et al., 2021, Effects of Insomnia on Peptic Ulcer Disease Using Mendelian Randomization. Oxidative Medicine and Cellular Longevity, 2021(2216314): 11. https://doi.org/10.1155/2021/2216314

Semple JI, Newton JL, Westley BR, et al., 2001, Dramatic Diurnal Variation in the concentration of the Human Trefoil Peptide TFF2 in Gastric Juice. Gut, 2001(48): 648–655. https://doi.org/10.1136/gut.48.5.648

Phull PS, Green CJ, Jacyna MR, 1995, A Radical View of the Stomach: The Role of Oxygen-derived Free Radicals and anti-oxidants in Gastroduodenal Disease. European Journal of Gastroenterology & Hepatology, 1995(7): 265–274.

Zimmermann P, Kurth S, Pugin B, et al., 2024, Microbial Melatonin Metabolism in the Human Intestine as a Therapeutic Target for Dysbiosis and Rhythm Disorders. NPJ Biofilms Microbiomes, 2024(10): 139. https://doi.org/10.1038/s41522-024-00605-6

Mei Q, Yu JP, Xu JM, et al., 2002, Melatonin Reduces Colon Immunological Injury in Rats by Regulating Activity of Macrophages. cta Pharmacologica Sinica, 2002(23): 882–886.

Baser KHC, Haskologlu IC, Erdag E, 2025, Molecular Links Between Circadian Rhythm Disruption, Melatonin, and Neurodegenerative Diseases: An Updated Review. Molecules, 30(9): 1888. https://doi.org/10.3390/molecules30091888

Kato K, Murai I, Asai S, et al., 2002, Circadian Rhythm of Melatonin and Prostaglandin in Modulation of Stress-induced Gastric Mucosal Lesions in Rats. Alimentary Pharmacology & Therapeutics, 2002(16): 29–34. https://doi.org/10.1046/j.1365-2036.16.s2.11.x

Jha LK, Fass R, Gadam R, et al., 2016, The Effect of Ramelteon on Heartburn Symptoms of Patients With Gastroesophageal Reflux Disease and Chronic Insomnia: A Pilot Study. Journal of Clinical Gastroenterology, 2016(50): e19–24. https://doi.org/10.1097/mcg.0000000000000322

Zhang WX, Zhu F, Hu R, 2017, Effects of Total Saponins from Lilium on Serum Brain-Gut Peptide Levels in Rats with Insomnia and Gastrointestinal Dysmotility. Journal of Hebei North University (Natural Science Edition), 2017(33): 25–26 + 29.

Huang WY, Zou X, Lu FE, et al., 2017, Effect of Jiaotai Pill on Intestinal Damage in Partially Sleep Deprived Rats. Chinese Journal of Integrative Medicine, 2017(23): 901–907. https://doi.org/10.1007/s11655-017-2969-8

Zhang YT, Qin S, Wang XQ, et al., 2025, The Scientific Connotation of “Heart and Brain Jointly Governing the Mind” and its Application in Acupuncture Treatment of Insomnia. Journal of Nanjing University of Chinese Medicine, 2025(41): 181–188. https://doi.org/10.14148/j.issn.1672-0482.2025.0181

Cui MJ, Chen YY, Liu C, et al., 2025, Clinical Study on Acupuncture Combined with Medication to Improve Blood Pressure Variability in Patients with Primary Hypertension. Journal of Shaanxi University of Chinese Medicine, 2025(48): 112–118. https://doi.org/10.13424/j.cnki.jsctcm.2025.01.018

Pan LM, Hong, ZB, Guan RQ, 2024, Research Progress on Insomnia Treated by Traditional Chinese Medicine and Acupuncture Based on Microbial-gut-brain Axis Theory. World Journal of Clinical Cases, 2024(12): 3314–3320. https://doi.org/10.12998/wjcc.v12.i18.3314

Liu Z, Zhao N, Xie C, et al., 2016, Effects of Electroacupuncture on Sleep-wake Circadian Rhythm and Melatonin Rhythm in Insomnia Rats. Chinese Journal of Traditional Chinese Medicine, 2016(31): 3695–3699.

Wang C, Sun XY, Xiu Y, et al., 2023, Effects of Electroacupuncture on the Expression of Hepatic Clock and Bmal1 Genes in C57BL/6J Mice with Circadian Rhythm Disruption. Chinese Archives of Traditional Chinese Medicine, 2023(41): 243–248. https://doi.org/10.13193/j.issn.1673-7717.2023.08.051

Wang ZW, Chen BW, Chen SZ, et al., 2023, Effects of Electroacupuncture at “Zusanli” (ST36) Combined with “Tianshu” (ST25) on Colonic Function and Autonomic Nerve Balance in Rats with Irritable Bowel Syndrome. Acupuncture Research, 2023(48): 165–171. https://doi.org/10.13702/j.1000-0607.20211324

Yan Y, Jin X, Zheng SX, et al., 2025, Effects of Acupuncture at Shenmen (HT7) Combined with Electroacupuncture at Front-mu Points on Intestinal Motility in Diarrhea-Predominant Irritable Bowel Syndrome. Journal of Shanxi University of Chinese Medicine, 2025(26): 555–561. https://doi.org/10.19763/j.cnki.2096-7403.2025.05.16

Yao XM, 2007, Effect of Acupuncture on Gastric Motility, Visceral Sensation, Electrogastrogram and Autonomic Nerve Function in Patients with Functional Dyspepsia, thesis, Hebei Medical University.

Wang XQ, Qin S, Wu WZ, et al., 2021, Electroacupuncture for Insomnia in the Elderly and Its Effect on Serum Melatonin and Dopamine. Chinese Acupuncture & Moxibustion, 2021(41): 501–504. https://doi.org/10.13703/j.0255-2930.20200404-k0001

Okudaira K, Furuta T, Shirai N, et al., 2005, Concomitant Dosing of Famotidine with a Triple Therapy Increases the Cure Rates of Helicobacter pylori Infections in Patients with the Homozygous Extensive Metabolizer Genotype of CYP2C19. Alimentary Pharmacology & Therapeutics, 2005(21): 491–497. https://doi.org/10.1111/j.1365-2036.2005.02353.x

Ran Q, Wu X, Hong XJ, 2011, Research Progress on Acupuncture and Moxibustion Treatment of Circadian Rhythm Sleep-wake Disorders. Journal of Liaoning University of Traditional Chinese Medicine, 2011(38): 570–572. https://doi.org/10.13192/j.ljtcm.2011.03.191.ranx.023

Xu Y, 2021, Bibliometric Study and Acupoint Selection Rule Analysis of Acupuncture and Moxibustion for Circadian Rhythm Insomnia, thesis, Liaoning University of Traditional Chinese Medicine.

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