Melatonin regulation as a possible mechanism for probiotic (VSL#3) in irritable bowel syndrome: a randomized double-blinded placebo study

Dig Dis Sci. 2015 Jan;60(1):186-94. doi: 10.1007/s10620-014-3299-8. Epub 2014 Aug 5.


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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Double-Blind Method
  • Female
  • Humans
  • Irritable Bowel Syndrome / physiopathology*
  • Irritable Bowel Syndrome / therapy*
  • Male
  • Melatonin / biosynthesis
  • Melatonin / physiology*
  • Middle Aged
  • Probiotics / chemistry
  • Probiotics / therapeutic use*
  • Rectum / physiopathology
  • Saliva / chemistry
  • Sensory Thresholds
  • Sleep / physiology
  • Treatment Outcome
  • Young Adult


  • Melatonin