Skip to main content

Advertisement

Log in

Role of biological rhythms in gastrointestinal health and disease

  • Published:
Reviews in Endocrine and Metabolic Disorders Aims and scope Submit manuscript

Abstract

The molecular basis for biological rhythms is formed by clock genes. Clock genes are functional in the liver, within gastrointestinal epithelial cells and neurons of the enteric nervous system. These observations suggest a possible role for clock genes in various circadian functions of the liver and the gastrointestinal tract through the modulation of organ specific clock-controlled genes. Consequently, disruptions in circadian rhythmicity may lead to adverse health consequences. This review will focus on the current understanding of the role of circadian rhythms in the pathogenesis of gastrointestinal- and hepatic disease such as obesity, non-alcoholic fatty liver disease, alcoholic fatty liver disease and alterations in colonic motility.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Brown SA, Schibler U. The ins and outs of circadian timekeeping. Curr Opin Genet Dev. 1999;9:588–94.

    Article  CAS  PubMed  Google Scholar 

  2. Bell-Pedersen D, Cassone VM, Earnest DJ, Golden SS, Hardin PE, Thomas TL, et al. Circadian rhythms from multiple oscillators: lessons from diverse organisms. Nat Rev Genet. 2005;6:544–56.

    Article  CAS  PubMed  Google Scholar 

  3. Lowrey PL, Takahashi JS. Mammalian circadian biology: elucidating genome-wide levels of temporal organization. Annu Rev Genomics Hum Genet. 2004;5:407–41.

    Article  CAS  PubMed  Google Scholar 

  4. Siepka SM, Yoo SH, Park J, Lee C, Takahashi JS. Genetics and neurobiology of circadian clocks in mammals. Cold Spring Harb Symp Quant Biol. 2007;72:251–9.

    Article  CAS  PubMed  Google Scholar 

  5. Hoogerwerf WA. Biologic clocks and the gut. Curr Gastroenterol Rep. 2006;8:353–9.

    Article  PubMed  Google Scholar 

  6. Halberg F, Haus E, Cornelissen G. From Biologic rhythms to chronomes relevant for nutrition. In: Marriott B, editor. Not eating enough: Overcoming underconsumption of military operational rations. Washington, DC: National Academy; 1995. p. 361–72.

    Google Scholar 

  7. Hirsch E, Halberg E, Halberg F, Goetz FC, Cressey D, Wendt H, et al. Body weight change during 1 week on a single daily 2, 000-calorie meal consumed as breakfast (B) or dinner (D). Chronobiologia. 1975;2:31–2.

    Google Scholar 

  8. Karlsson B, Knutsson A, Lindahl B. Is there an association between shift work and having a metabolic syndrome? Results from a population based study of 27,485 people. Occup Environ Med. 2001;58:747–52.

    Article  CAS  PubMed  Google Scholar 

  9. Morikawa Y, Nakagawa H, Miura K, Soyama Y, Ishizaki M, Kido T, et al. Effect of shift work on body mass index and metabolic parameters. Scand J Work Environ Health. 2007;33:45–50.

    PubMed  Google Scholar 

  10. Dallman MF, Engeland WC, Rose JC, Wilkinson CW, Shinsako J, Siedenburg F. Nycthemeral rhythm in adrenal responsiveness to ACTH. Am J Physiol. 1978;235:R210–8.

    CAS  PubMed  Google Scholar 

  11. Dallman MF, Strack AM, Akana SF, Bradbury MJ, Hanson ES, Scribner KA, et al. Feast and famine: critical role of glucocorticoids with insulin in daily energy flow. Front Neuroendocrinol. 1993;14:303–47.

    Article  CAS  PubMed  Google Scholar 

  12. Jasper MS, Engeland WC. Splanchnic neural activity modulates ultradian and circadian rhythms in adrenocortical secretion in awake rats. Neuroendocrinology. 1994;59:97–109.

    Article  CAS  PubMed  Google Scholar 

  13. Moore RY, Eichler VB. Loss of a circadian adrenal corticosterone rhythm following suprachiasmatic lesions in the rat. Brain Res. 1972;42:201–6.

    Article  CAS  PubMed  Google Scholar 

  14. Nagai K, Nishio T, Nakagawa H, Nakamura S, Fukuda Y. Effect of bilateral lesions of the suprachiasmatic nuclei on the circadian rhythm of food-intake. Brain Res. 1978;142:384–9.

    Article  CAS  PubMed  Google Scholar 

  15. Tataranni PA, Larson DE, Snitker S, Young JB, Flatt JP, Ravussin E. Effects of glucocorticoids on energy metabolism and food intake in humans. Am J Physiol. 1996;271:E317–25.

    CAS  PubMed  Google Scholar 

  16. Bjorntorp P, Rosmond R. Obesity and cortisol. Nutrition. 2000;16:924–36.

    Article  CAS  PubMed  Google Scholar 

  17. Koska J, de Courten B, Wake DJ, Nair S, Walker BR, Bunt JC, et al. 11beta-hydroxysteroid dehydrogenase type 1 in adipose tissue and prospective changes in body weight and insulin resistance. Obesity (Silver Spring). 2006;14:1515–22.

    Article  CAS  Google Scholar 

  18. Livingstone DE, Jones GC, Smith K, Jamieson PM, Andrew R, Kenyon CJ, et al. Understanding the role of glucocorticoids in obesity: tissue-specific alterations of corticosterone metabolism in obese Zucker rats. Endocrinology. 2000;141:560–3.

    Article  CAS  PubMed  Google Scholar 

  19. Livingstone DE, Kenyon CJ, Walker BR. Mechanisms of dysregulation of 11 beta-hydroxysteroid dehydrogenase type 1 in obese Zucker rats. J Endocrinol. 2000;167:533–9.

    Article  CAS  PubMed  Google Scholar 

  20. Dallman MF, Pecoraro N, Akana SF, La Fleur SE, Gomez F, Houshyar H, et al. Chronic stress and obesity: a new view of “comfort food”. Proc Natl Acad Sci USA. 2003;100:11696–701.

    Article  CAS  PubMed  Google Scholar 

  21. Scheer FA, Hilton MF, Mantzoros CS, Shea SA. Adverse metabolic and cardiovascular consequences of circadian misalignment. Proc Natl Acad Sci USA. 2009;106:4453–8.

    Article  CAS  PubMed  Google Scholar 

  22. Byrne CD, Olufadi R, Bruce KD, Cagampang FR, Ahmed MH. Metabolic disturbances in non-alcoholic fatty liver disease. Clin Sci (Lond). 2009;116:539–64.

    Article  CAS  Google Scholar 

  23. Vuppalanchi R, Chalasani N. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: Selected practical issues in their evaluation and management. Hepatology. 2009;49:306–17.

    Article  PubMed  Google Scholar 

  24. Postic C, Girard J. Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice. J Clin Invest. 2008;118:829–38.

    Article  CAS  PubMed  Google Scholar 

  25. Panda S, Antoch MP, Miller BH, Su AI, Schook AB, Straume M, et al. Coordinated transcription of key pathways in the mouse by the circadian clock. Cell. 2002;109:307–20.

    Article  CAS  PubMed  Google Scholar 

  26. Storch KF, Lipan O, Leykin I, Viswanathan N, Davis FC, Wong WH, et al. Extensive and divergent circadian gene expression in liver and heart. Nature. 2002;417:78–83.

    Article  CAS  PubMed  Google Scholar 

  27. Yang X, Downes M, Yu RT, Bookout AL, He W, Straume M, et al. Nuclear receptor expression links the circadian clock to metabolism. Cell. 2006;126:801–10.

    Article  CAS  PubMed  Google Scholar 

  28. Turek FW, Joshu C, Kohsaka A, Lin E, Ivanova G, McDearmon E, et al. Obesity and metabolic syndrome in circadian Clock mutant mice. Science. 2005;308:1043–5.

    Article  CAS  PubMed  Google Scholar 

  29. Ando H, Yanagihara H, Hayashi Y, Obi Y, Tsuruoka S, Takamura T, et al. Rhythmic messenger ribonucleic acid expression of clock genes and adipocytokines in mouse visceral adipose tissue. Endocrinology. 2005;146:5631–6.

    Article  CAS  PubMed  Google Scholar 

  30. Fontaine C, Dubois G, Duguay Y, Helledie T, Vu-Dac N, Gervois P, et al. The orphan nuclear receptor Rev-Erbalpha is a peroxisome proliferator-activated receptor (PPAR) gamma target gene and promotes PPARgamma-induced adipocyte differentiation. J Biol Chem. 2003;278:37672–80.

    Article  CAS  PubMed  Google Scholar 

  31. Ando H, Takamura T, Matsuzawa-Nagata N, Shima KR, Nakamura S, Kumazaki M, et al. The hepatic circadian clock is preserved in a lipid-induced mouse model of non-alcoholic steatohepatitis. Biochem Biophys Res Commun. 2009;380:684–8.

    Article  CAS  PubMed  Google Scholar 

  32. Sookoian S, Castano G, Gemma C, Gianotti TF, Pirola CJ. Common genetic variations in CLOCK transcription factor are associated with nonalcoholic fatty liver disease. World J Gastroenterol. 2007;13:4242–8.

    CAS  PubMed  Google Scholar 

  33. Kudo T, Tamagawa T, Shibata S. Effect of chronic ethanol exposure on the liver of Clock-mutant mice. J Circadian Rhythms. 2009;7:4.

    PubMed  Google Scholar 

  34. Deimling MJ, Schnell RC. Circadian rhythms in the biological response and disposition of ethanol in the mouse. J Pharmacol Exp Ther. 1980;213:1–8.

    CAS  PubMed  Google Scholar 

  35. Salsano F, Maly IP, Sasse D. The circadian rhythm of intra-acinar profiles of alcohol dehydrogenase activity in rat liver: a microquantitative study. Histochem J. 1990;22:395–400.

    Article  CAS  PubMed  Google Scholar 

  36. Stearns AT, Balakrishnan A, Rhoads DB, Ashley SW, Tavakkolizadeh A. Diurnal expression of the rat intestinal sodium-glucose cotransporter 1 (SGLT1) is independent of local luminal factors. Surgery. 2009;145:294–302.

    Article  PubMed  Google Scholar 

  37. Saito H, Terada T, Shimakura J, Katsura T, Inui K. Regulatory mechanism governing the diurnal rhythm of intestinal H+/peptide cotransporter 1 (PEPT1). Am J Physiol.: Gastrointest Liver Physiol. 2008;295:G395–402.

    Article  CAS  Google Scholar 

  38. Pan X, Terada T, Okuda M, Inui K. Altered diurnal rhythm of intestinal peptide transporter by fasting and its effects on the pharmacokinetics of ceftibuten. J Pharmacol Exp Ther. 2003;307:626–32.

    Article  CAS  PubMed  Google Scholar 

  39. Tavakkolizadeh A, Ramsanahie A, Levitsky LL, Zinner MJ, Whang EE, Ashley SW, et al. Differential role of vagus nerve in maintaining diurnal gene expression rhythms in the proximal small intestine. J Surg Res. 2005;129:73–8.

    Article  CAS  PubMed  Google Scholar 

  40. Hoogerwerf WA, Hellmich HL, Cornelissen G, Halberg F, Shahinian VB, Bostwick J, et al. Clock gene expression in the murine gastrointestinal tract: endogenous rhythmicity and effects of a feeding regimen. Gastroenterology. 2007;133:1250–60.

    Article  CAS  PubMed  Google Scholar 

  41. Auwerda JJ, Bac DJ, Schouten WR. Circadian rhythm of rectal motor complexes. Dis Colon Rectum. 2001;44:1328–32.

    Article  CAS  PubMed  Google Scholar 

  42. Bassotti G, Iantorno G, Fiorella S, Bustos-Fernandez L, Bilder CR. Colonic motility in man: features in normal subjects and in patients with chronic idiopathic constipation. Am J Gastroenterol. 1999;94:1760–70.

    Article  CAS  PubMed  Google Scholar 

  43. Frexinos J, Bueno L, Fioramonti J. Diurnal changes in myoelectric spiking activity of the human colon. Gastroenterology. 1985;88:1104–10.

    CAS  PubMed  Google Scholar 

  44. Rao SS, Sadeghi P, Beaty J, Kavlock R, Ackerson K. Ambulatory 24-h colonic manometry in healthy humans. Am J Physiol: Gastrointest Liver Physiol. 2001;280:G629–39.

    CAS  Google Scholar 

  45. Caruso CC, Lusk SL, Gillespie BW. Relationship of work schedules to gastrointestinal diagnoses, symptoms, and medication use in auto factory workers. Am J Ind Med. 2004;46:586–98.

    Article  PubMed  Google Scholar 

  46. Cassone VM, Stephan FK. Central and peripheral regulation of feeding and nutrition by the mammalian circadian clock: implications for nutrition during manned space flight. Nutrition. 2002;18:814–9.

    Article  PubMed  Google Scholar 

  47. Costa G. The impact of shift and night work on health. Appl Ergon. 1996;27:9–16.

    Article  CAS  PubMed  Google Scholar 

  48. Knutsson A. Health disorders of shift workers. Occup Med (Lond). 2003;53:103–8.

    Article  Google Scholar 

  49. Vener KJ, Szabo S, Moore JG. The effect of shift work on gastrointestinal (GI) function: a review. Chronobiologia. 1989;16:421–39.

    CAS  PubMed  Google Scholar 

  50. Sladek M, Rybova M, Jindrakova Z, Zemanova Z, Polidarova L, Mrnka L, et al. Insight into the circadian clock within rat colonic epithelial cells. Gastroenterology. 2007;133:1240–9.

    Article  CAS  PubMed  Google Scholar 

  51. Hoogerwerf WA, Sinha M, Conesa A, Luxon BA, Shahinian VB, Cornelissen G, et al. Transcriptional Profiling of mRNA Expression in the Mouse Distal Colon. Gastroenterology 2008.

  52. Lu WZ, Gwee KA, Ho KY. Functional bowel disorders in rotating shift nurses may be related to sleep disturbances. Eur J Gastroenterol Hepatol. 2006;18:623–7.

    Article  Google Scholar 

  53. Nojkov BR, J. Hoogerwerf, S. Chey, WD. The Effect of Shift Work on the Prevalence and Clinical Impact of Functional Bowel Disorders in Nurses. Am J Gastroenterol 2008.

  54. Gwee KA. Irritable bowel syndrome in developing countries—a disorder of civilization or colonization? Neurogastroenterol Motil. 2005;17:317–24.

    Article  PubMed  Google Scholar 

  55. Corney RH, Stanton R. Physical symptom severity, psychological and social dysfunction in a series of outpatients with irritable bowel syndrome. J Psychosom Res. 1990;34:483–91.

    Article  CAS  PubMed  Google Scholar 

  56. Fass R, Fullerton S, Tung S, Mayer EA. Sleep disturbances in clinic patients with functional bowel disorders. Am J Gastroenterol. 2000;95:1195–2000.

    Article  CAS  PubMed  Google Scholar 

  57. Nyhlin H, Ford MJ, Eastwood J, Smith JH, Nicol EF, Elton RA, et al. Non-alimentary aspects of the irritable bowel syndrome. J Psychosom Res. 1993;37:155–62.

    Article  CAS  PubMed  Google Scholar 

  58. Goldsmith G, Levin JS. Effect of sleep quality on symptoms of irritable bowel syndrome. Dig Dis Sci. 1993;38:1809–14.

    Article  CAS  PubMed  Google Scholar 

  59. Jarrett M, Heitkemper M, Cain KC, Burr RL, Hertig V. Sleep disturbance influences gastrointestinal symptoms in women with irritable bowel syndrome. Dig Dis Sci. 2000;45:952–9.

    Article  CAS  PubMed  Google Scholar 

  60. Burioka N, Koyanagi S, Endo M, Takata M, Fukuoka Y, Miyata M, et al. Clock gene dysfunction in patients with obstructive sleep apnoea syndrome. Eur Respir J. 2008;32:105–12.

    Article  CAS  PubMed  Google Scholar 

  61. Mistlberger RE. Circadian regulation of sleep in mammals: role of the suprachiasmatic nucleus. Brain Res Brain Res Rev. 2005;49:429–54.

    Article  PubMed  Google Scholar 

  62. Lu WZ, Gwee KA, Moochhalla S, Ho KY. Melatonin improves bowel symptoms in female patients with irritable bowel syndrome: a double-blind placebo-controlled study. Aliment Pharmacol Ther. 2005;22:927–34.

    Article  CAS  PubMed  Google Scholar 

  63. Enck P, Kaiser C, Felber M, Riepl RL, Klauser A, Klosterhalfen S, et al. Circadian variation of rectal sensitivity and gastrointestinal peptides in healthy volunteers. Neurogastroenterol Motil 2008.

  64. Chang L, Sundaresh S, Elliott J, Anton PA, Baldi P, Licudine A, et al. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in irritable bowel syndrome. Neurogastroenterol Motil. 2009;21:149–59.

    Article  CAS  PubMed  Google Scholar 

  65. Tebbe JJ, Pasat IR, Monnikes H, Ritter M, Kobelt P, Schafer MK. Excitatory stimulation of neurons in the arcuate nucleus initiates central CRF-dependent stimulation of colonic propulsion in rats. Brain Res. 2005;1036:130–8.

    Article  CAS  PubMed  Google Scholar 

  66. Stengel A, Tache Y. Neuroendocrine control of the gut during stress: corticotropin-releasing factor signaling pathways in the spotlight. Annu Rev Physiol 2008.

  67. Gue M, Junien JL, Bueno L. Conditioned emotional response in rats enhances colonic motility through the central release of corticotropin-releasing factor. Gastroenterology. 1991;100:964–70.

    CAS  PubMed  Google Scholar 

  68. Chatzaki E, Crowe PD, Wang L, Million M, Tache Y, Grigoriadis DE. CRF receptor type 1 and 2 expression and anatomical distribution in the rat colon. J Neurochem. 2004;90:309–16.

    Article  CAS  PubMed  Google Scholar 

  69. Yuan PQ, Million M, Wu SV, Rivier J, Tache Y. Peripheral corticotropin releasing factor (CRF) and a novel CRF1 receptor agonist, stressin1-A activate CRF1 receptor expressing cholinergic and nitrergic myenteric neurons selectively in the colon of conscious rats. Neurogastroenterol Motil. 2007;19:923–36.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work is supported by R21 DK074477 and the Michigan Gastrointestinal Peptide Research Center.

Financial disclosures

None of the authors have a conflict of interest to disclose

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Willemijntje A. Hoogerwerf.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hoogerwerf, W.A. Role of biological rhythms in gastrointestinal health and disease. Rev Endocr Metab Disord 10, 293–300 (2009). https://doi.org/10.1007/s11154-009-9119-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11154-009-9119-3

Keywords

Navigation