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Melatonin Regulation as a Possible Mechanism for Probiotic (VSL#3) in Irritable Bowel Syndrome: A Randomized Double-Blinded Placebo Study

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Abstract

Background

Probiotics have treatment efficacy in irritable bowel syndrome (IBS), but the exact mechanism remains obscure. One hypothesis is the mediation of melatonin levels, leading to changes in IBS symptoms.

Aim

The purpose of this study was to evaluate the effects of a probiotic, VSL#3, on symptoms, psychological and sleep parameters, and pain sensitivity in IBS, and relate these parameters to in vivo melatonin levels.

Methods

Forty-two IBS patients were randomly assigned to receive VSL#3 or placebo for 6 weeks. Subjects completed bowel and psychological questionnaires, underwent rectal sensitivity testing and saliva melatonin assays.

Results

Abdominal pain duration and distension intensity decreased significantly in the probiotic group, along with an increase in rectal distension pain thresholds. A correlation between increase in pain tolerance and improvement in abdominal pain scores (r = 0.51, p = 0.02) was seen with probiotic. There was an increase in salivary morning melatonin levels in males treated with VSL#3, which correlated (r = 0.61) with improved satisfaction in bowel habits. When grouped based on baseline diurnal melatonin levels, patients with normal diurnal fluctuations showed an increase in morning melatonin levels with VSL#3 treatment, which significantly correlated with improved satisfaction in bowel habits (r = 0.68). They also had reduced symptom severity scores and abdominal pain duration when treated with VSL#3, as well as satisfaction with bowel movements and quality-of-life.

Conclusions

VSL#3 improved symptoms and increased rectal pain thresholds. Symptom improvement correlated with a rise in morning melatonin, significant in males and subjects with normal circadian rhythm. This suggests that probiotics may act by influencing melatonin production, hence modulating IBS symptoms, in individuals with a normal circadian rhythm.

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References

  1. Farthing MJ. Irritable bowel, irritable body, or irritable brain? BMJ. 1995;310:171–175.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Gwee KA, Wee S, Wong ML, Png DJ. The prevalence, symptom characteristics, and impact of irritable bowel syndrome in an asian urban community. Am J Gastroenterol. 2004;99:924–931.

  3. Matto J, Maunuksela L, Kajander K, et al. Composition and temporal stability of gastrointestinal microbiota in irritable bowel syndrome–a longitudinal study in IBS and control subjects. FEMS Immunol Med Microbiol. 2005;43:213–222.

    Article  PubMed  Google Scholar 

  4. Malinen E, Rinttila T, Kajander K, et al. Analysis of the fecal microbiota of irritable bowel syndrome patients and healthy controls with real-time PCR. Am J Gastroenterol. 2005;100:373–382.

    Article  CAS  PubMed  Google Scholar 

  5. Kim HJ, Vazquez Roque MI, Camilleri M, et al. A randomized controlled trial of a probiotic combination VSL#3 and placebo in irritable bowel syndrome with bloating. Neurogastroenterol Motil. 2005;17:687–696.

    Article  CAS  PubMed  Google Scholar 

  6. O’Mahony L, McCarthy J, Kelly P, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology. 2005;128:541–551.

    Article  PubMed  Google Scholar 

  7. King TS, Elia M, Hunter JO. Abnormal colonic fermentation in irritable bowel syndrome. Lancet. 1998;352:1187–1189.

    Article  CAS  PubMed  Google Scholar 

  8. Treem WR, Ahsan N, Kastoff G, Hyams JS. Fecal short-chain fatty acids in patients with diarrhea-predominant irritable bowel syndrome: in vitro studies of carbohydrate fermentation. J Pediatr Gastroenterol Nutr. 1996;23:280–286.

    Article  CAS  PubMed  Google Scholar 

  9. Lamine F, Eutamene H, Fioramonti J, Bueno L, Theodorou V. Colonic responses to Lactobacillus farciminis treatment in trinitrobenzene sulphonic acid-induced colitis in rats. Scand J Gastroenterol. 2004;39:1250–1258.

    Article  CAS  PubMed  Google Scholar 

  10. Sartor RB. Therapeutic manipulation of the enteric microflora in inflammatory bowel diseases: antibiotics, probiotics, and prebiotics. Gastroenterology. 2004;126:1620–1633.

    Article  PubMed  Google Scholar 

  11. Weinryb RM, Osterberg E, Blomquist L, Hultcrantz R, Krakau I, Asberg M. Psychological factors in irritable bowel syndrome: a population-based study of patients, non-patients and controls. Scand J Gastroenterol. 2003;38:503–510.

    Article  CAS  PubMed  Google Scholar 

  12. Patacchioli FR, Angelucci L, Dellerba G, Monnazzi P, Leri O. Actual stress, psychopathology and salivary cortisol levels in the irritable bowel syndrome (IBS). J Endocrinol Invest. 2001;24:173–177.

    Article  CAS  PubMed  Google Scholar 

  13. Kellner M, Yassouridis A, Manz B, Steiger A, Holsboer F, Wiedemann K. Corticotropin-releasing hormone inhibits melatonin secretion in healthy volunteers—a potential link to low-melatonin syndrome in depression? Neuroendocrinology. 1997;65:284–290.

    Article  CAS  PubMed  Google Scholar 

  14. Song GH, Leng PH, Gwee KA, Moochhala SM, Ho KY. Melatonin improves abdominal pain in irritable bowel syndrome patients who have sleep disturbances: a randomised, double blind, placebo controlled study. Gut. 2005;54:1402–1407.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. 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;22:927–934.

    Article  CAS  PubMed  Google Scholar 

  16. Bubenik GA. Gastrointestinal melatonin: localization, function, and clinical relevance. Dig Dis Sci. 2002;47:2336–2348.

    Article  CAS  PubMed  Google Scholar 

  17. Drossman DA, Dumitrascu DL. Rome III: new standard for functional gastrointestinal disorders. J Gastrointestin Liver Dis. 2006;15:237–241.

    PubMed  Google Scholar 

  18. Talley NJ, Phillips SF, Melton J 3rd, Wiltgen C, Zinsmeister AR. A patient questionnaire to identify bowel disease. Ann Intern Med. 1989;111:671–674.

    Article  CAS  PubMed  Google Scholar 

  19. Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989;28:193–213.

    Article  CAS  PubMed  Google Scholar 

  20. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67:361–370.

    Article  CAS  PubMed  Google Scholar 

  21. Camilleri M. Drugs targeting functional bowel disorders: lessons from drug trials. Curr Opin Pharmacol. 2002;2:684–690.

    Article  CAS  PubMed  Google Scholar 

  22. Song GH, Venkatraman V, Ho KY, Chee MW, Yeoh KG, Wilder-Smith CH. Cortical effects of anticipation and endogenous modulation of visceral pain assessed by functional brain MRI in irritable bowel syndrome patients and healthy controls. Pain. 2006;126:79–90.

    Article  PubMed  Google Scholar 

  23. Francis CY, Morris J, Whorwell PJ. The irritable bowel severity scoring system: a simple method of monitoring irritable bowel syndrome and its progress. Aliment Pharmacol Ther. 1997;11:395–402.

    Article  CAS  PubMed  Google Scholar 

  24. Hirano S, Ono M, Aimoto A. Functional and biochemical effects on rat lung following instillation of crocidolite and chrysotile asbestos. J Toxicol Environ Health. 1988;24:27–39.

    Article  CAS  PubMed  Google Scholar 

  25. McKernan DP, Fitzgerald P, Dinan TG, Cryan JF. The probiotic Bifidobacterium infantis 35624 displays visceral antinociceptive effects in the rat. Neurogastroenterol Motil. 2010;22:e268.

    Article  Google Scholar 

  26. Wilder-Smith CH, Schindler D, Lovblad K, Redmond SM, Nirkko A. Brain functional magnetic resonance imaging of rectal pain and activation of endogenous inhibitory mechanisms in irritable bowel syndrome patient subgroups and healthy controls. Gut. 2004;53:1595–1601.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Wilder-Smith CH, Robert-Yap J. Abnormal endogenous pain modulation and somatic and visceral hypersensitivity in female patients with irritable bowel syndrome. World J Gastroenterol. 2007;13:3699–3704.

    PubMed Central  PubMed  Google Scholar 

  28. Heymen S, Maixner W, Whitehead WE, Klatzkin RR, Mechlin B, Light KC. Central processing of noxious somatic stimuli in patients with irritable bowel syndrome compared with healthy controls. Clin J Pain. 2010;26:104–109.

    Article  PubMed  Google Scholar 

  29. Piche M, Arsenault M, Poitras P, Rainville P, Bouin M. Widespread hypersensitivity is related to altered pain inhibition processes in irritable bowel syndrome. Pain. 2010;148:49–58.

    Article  PubMed  Google Scholar 

  30. Wilder-Smith CH, Song G, Yeoh KG, Ho KY. Activating endogenous visceral pain modulation: a comparison of heterotopic stimulation methods in healthy controls. Eur J Pain. 2009;13:836–842.

    Article  PubMed  Google Scholar 

  31. Guerrero JM, Reiter RJ. Melatonin-immune system relationships. Curr Top Med Chem. 2002;2:167–179.

    Article  CAS  PubMed  Google Scholar 

  32. Klupinska G, Wisniewska-Jarosinska M, Harasiuk A, et al. Nocturnal secretion of melatonin in patients with upper digestive tract disorders. J Physiol Pharmacol. 2006;57:41–50.

    PubMed  Google Scholar 

  33. Houghton LA, Heyman DJ, Whorwell PJ. Symptomatology, quality of life and economic features of irritable bowel syndrome–the effect of hypnotherapy. Aliment Pharmacol Ther. 1996;10:91–95.

    Article  CAS  PubMed  Google Scholar 

  34. Radwan P, Skrzydlo-Radomanska B, Radwan-Kwiatek K, Burak-Czapiuk B, Strzemecka J. Is melatonin involved in the irritable bowel syndrome? J Physiol Pharmacol. 2009;60:67–70.

    PubMed  Google Scholar 

  35. Cain SW, Dennison CF, Zeitzer JM, et al. Sex differences in phase angle of entrainment and melatonin amplitude in humans. J Biol Rhythms. 2010;25:288–296.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Correspondence to Reuben K. Wong.

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Wong, R.K., Yang, C., Song, GH. et al. Melatonin Regulation as a Possible Mechanism for Probiotic (VSL#3) in Irritable Bowel Syndrome: A Randomized Double-Blinded Placebo Study. Dig Dis Sci 60, 186–194 (2015). https://doi.org/10.1007/s10620-014-3299-8

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  • DOI: https://doi.org/10.1007/s10620-014-3299-8

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