The Effect of Serotonergic Modulation on Intestinal Permeability and Visceral Hypersensitivity in Healthy Individuals and Irritable Bowel Syndrome (IBS) Patients

The Effect of Serotonergic Modulation on Intestinal Permeability and Visceral Hypersensitivity in Healthy Individuals and IBS Patients

Serotonin, 5-hydroxytryptamin (5-HT), plays an important role in regulating the gastrointestinal functions. In this study we will modulate the serotonin system with acute tryptophan depletion (ATD) and administration of 5-hydroxytryptophan (5-HTP). ATD is based on ingestion of an amino acid drink devoid of the precursor of serotonin and hence caused a decreased serotonin level. 5-hydroxy-tryptophan is the direct precursor of serotonin and its administration, an increased serotonin level is expected. During these interventions, gut permeability and visceral sensitivity will be measured in healthy individuals and patients with irritable bowel syndrome, which is characterized by altered permeability and visceral hypersensitivity.

Inclusion Criteria:

• IBS-patients

Inclusion criteria:

1. IBS will be diagnosed according to the Rome III criteria* [35]:

   Recurrent abdominal pain or discomfort at least 3 days per month in the last 3 months associated with 2 or more of the following:

   • Improvement with defecation

   • Onset associated with a change in frequency of stool

   • Onset associated with a change in form (appearance) of stool

     • Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis
     • Discomfort means an uncomfortable sensation not described as pain. In pathophysiological research and clinical trails, a pain/discomfort frequency of at least 2 days a week during screening evaluation is an indication for subject's eligibility.

2. Based on the medical history and previous examination, no other causes for the abdominal complaints can be defined.

3. Age between 18 and 65 years

Healthy individuals

Inclusion criteria:

All subjects will be screened with a standardized psychiatric examination using the mini international neuropsychiatric interview (MINI) to determine present psychiatric state. General psychological state will be assessed using the 17 item Hamilton depression rating scale (HAM-D17), the Dutch version of the symptom checklist (SCL-90) and the hospital anxiety and depression rating scale (HADS). The psychiatric evaluation will be carried out by a psychiatrist. Volunteers with deviating scores on any topic will be excluded from participation.

Healthy individuals between age 18 and 65 years will be included in the study.

Exclusion Criteria:

• Exclusion criteria for IBS patients:

  1. Severe co-morbidity hindering a rectal barostat procedure, according to the gastroenterologist's perception.
  2. Abdominal surgery, except for uncomplicated appendectomy, laparoscopic cholecystectomy or hysterectomy.
  3. Inability to stop medication that can influence gastrointestinal motility or perception (like loperamide, butylscopolamine, psylliumsead (metamucil), duspatal, metoclopramide, domperidon, erytromycine), or serotonin metabolism (carbidopa) for at least 3 days before tests.
  4. History of psychiatric disorders including use of psychoactive medication or psychological symptomatology, defined as a diagnosis on the MINI, HAM-D17 score above 18, global severity index score on SCL-90 for females ≥150, for males ≥131, or HADS scores ≥ 8. First-degree family members with psychiatric disorders
  5. Administration of investigational drugs in the 180 days prior to the study
  6. Premenstrual syndrome, dieting, pregnancy, lactation
  7. Excessive alcohol consumption (>20 alcoholic consumption per week)
  8. Smoking
  9. Blood donation within 3 months before the study period
  10. Self-admitted HIV-positive state
  11. Irregular day-night rhythm

Exclusion criteria for healthy individuals:

1. History of gastrointestinal, psychiatric disorders including use of psychoactive medication or psychological symptomatology, defined as a diagnosis on the MINI, HAM-D17 score above 18, global severity index score on SCL-90 for females ≥150, for males ≥131, or HADS scores ≥ 8 First-degree family members with psychiatric disorders
2. Use of medication, except oral contraceptives, within 14 days prior to testing
3. Administration of investigational drugs in the 180 days prior to the study
4. Previous abdominal surgery (other than uncomplicated appendectomy, laparoscopic cholecystectomy and hysterectomy)
5. Premenstrual syndrome, dieting, pregnancy, lactation
6. Excessive alcohol consumption (>20 alcoholic consumption per week)
7. Smoking
8. Blood donation within 3 months before the study period
9. Self-admitted HIV-positive state
10. Irregular day-night rhythm
11. Severe co-morbidity hindering a rectal barostat procedure, according to the gastroenterologist's perception.