Effect of Serotonergic Stimulation on the Gut-brain Axis

Selective serotonin reuptake inhibitors increase the level of serotonin. This study will use functional magnetic resonance imaging to examine how subjects with, and without, irritable bowel syndrome patients respond to serotonergic stimulation. Brain activation during emotional and arithmetic tasks and during visceral pain will be measured after serotonergic stimulation using the oral administration of Escitalopram (10 mg). The investigators will further integrate background parameters of the irritable bowel syndrome subjects and healthy controls (such as microbiota composition, genetic markers of serotonergic and inflammatory pathways, intestinal permeability, state of mood and visceral sensitivity) with the responses to the various challenges on the level of functional brain imaging. These responses may reveal a 'footprint' of the individual gut-brain axis function. Analyses of these individual footprints in multiple subjects with and without irritable bowel syndrome may reveal biosignatures characterising certain groups of patients according to specific gut-brain signalling response patterns. These biosignatures may be used to develop an individualised treatment algorithm for irritable bowel syndrome therapy.

In this double-blinded, randomized, cross-over study, irritable bowel syndrome subjects (n = 40) and healthy controls (n = 20) will perform an emotional and the arithmetic task and receive visceral stimuli (by using a barostat) while placed in a functional magnetic resonance imaging scanner respectively during two different states, a) after oral administration of 10 mg Escitalopram, a well-known drug classified as Selective Serotonin Reuptake Inhibitor, packed in a coloured hydroxypropylmethylcellulose capsule, and b) during oral administration of a placebo, in a double-blinded randomized cross-over fashion. Background characteristics will be collected.

Eligibility Criteria:
Inclusion criteria for the irritable bowel syndrome group:

1. Subjects fulfill Rome IV diagnostic criteria for irritable bowel syndrome and pain frequency for at least 1 day per week in the last 12 weeks
2. Males or females aged 18-65 years
3. Signed informed consent

Exclusion criteria for the irritable bowel syndrome group:

1. Concurrent or recent treatment with drugs affecting intestinal microbiota, function or mood, e.g., antidepressants (\< 12 weeks), antibiotics (\< 12 weeks)
2. Concurrent or recent (\< 4 weeks) use of nutritional supplements or herb products affecting intestinal function or mood (e.g. aloe vera, St. John´s Wort and probiotics)
3. Diagnosis of major psychiatric or somatic disease other than part of irritable bowel syndrome
4. Suicidal tendencies according to Montgomery Åsberg Depression Ratings Scale and/or clinical judgment
5. Abuse of alcohol or drugs according to Alcohol Use Disorders Identification Test, and/or clinical judgment
6. Recent (\< 4 weeks) intake of proton pump inhibitors (e.g., omeprazole)
7. Epilepsy
8. Cerebral bleeding or history of cerebral bleeding
9. Pregnancy or breastfeeding (will be asked)
10. Claustrophobia
11. Smoking or using tobacco including snuff
12. Dominant left-hand
13. Medical implant (e.g., pacemaker)
14. Aneurysm clips in the head
15. Shunts in the head
16. Grenade-splinter or metal-splinter in the body (e.g., eyes)
17. Metal or electrodes in the body (e.g., temp-catheter, aorta stent, cochlear implant)
18. Comprehensive tooth-implants or prothesis
19. Operated in the head
20. Operated in the heart
21. Swallowed a video-capsule
22. Non-corrected astigmatism
23. Regular intake of antiinflammatory medication (including non-steroidal antiinflammatory drugs)
24. Visual defect without possibility to use lenses during functional magnetic resonance imaging scanning
25. Any other reason the investigator feels the subject is not suitable for participation in the study

Inclusion criteria for healthy group:

1. Males and females aged 18-65 years of age
2. Signed informed consent

Exclusion criteria for the healthy group:

1. Concurrent or recent history of gastrointestinal disorders or any somatic disorder
2. Concurrent or recent treatment with drugs affecting intestinal microbiota, function or mood, e.g., antidepressants (\< 12 weeks), antibiotics (\< 12 weeks)
3. Concurrent or recent (\< 4 weeks) use of nutritional supplements or herb products affecting intestinal function or mood (e.g. aloe vera, St. John´s Wort and probiotics)
4. Concurrent psychiatric or psychological symptomatology defined as above cut-off on Montgomery Åsberg Depression Ratings Scale, above clinical cut-off on hospital anxiety and depression scale (equal to or above 8)
5. Abuse of alcohol or drugs according to Alcohol Use Disorders Identification Test, and/or clinical judgment
6. Recent (\< 4 weeks) intake of proton pump inhibitors, (e.g., omeprazole)
7. Epilepsy
8. Cerebral bleeding or history of cerebral bleeding
9. Pregnancy or breastfeeding (will be asked)
10. Claustrophobia
11. Smoking or using tobacco including snuff
12. Dominant left-hand
13. Medical implant (e.g., pacemaker)
14. Aneurysm clips in the head
15. Shunts in the head
16. Grenade-splinter or metal-splinter in the body (e.g., eyes)
17. Metal or electrodes in the body (e.g., temp-catheter, aorta stent, cochlear implant)
18. Comprehensive tooth-implants or prothesis
19. Operated in the head
20. Operated in the heart
21. Swallowed a video-capsule
22. Non-corrected astigmatism
23. Intake of anti-inflammatory medication (including non-steroidal antiinflammatory drugs)
24. Visual defect without possibility to use lenses during functional magnetic resonance imaging scanning
25. Any other reason the investigator feels the subject is not suitable for participation in the study.