3b - STRESS & IBS

Question 1

Core concept of stress & IBS

Answer 1

CORE CONCEPT
- IBS = functional gastrointestinal (GI) disorder marked by abdominal pain/discomfort, altered stool patterns, with no
visible abnormalities
- Psychological stress = major contributing factor in both development & symptom exacerbation of IBS
- IBS increasingly recognized as involving dysregulation of brain-gut axis & more recently, microbiota-gut-brain axis

Question 2

Key physiological systems involved

Answer 2

Table

Question 3

Stress-related pathways in IBS:
- HPA axis activation
- neuro-immune crosstalk
- microbiota-gut brain axis

Answer 3

STRESS-RELATED PATHWAYS IN IBS
HPA Axis Activation
- Stress → hypothalamus releases CRF → stimulates pituitary to release ACTH → adrenal glands release cortisol
- Cortisol alters gut motility, increases permeability & affects immune activation

Neuro-immune Crosstalk
- Mast cells, enterochromaffin (EC) cells & cytokines mediate inflammation & visceral hypersensitivity.
- CRF also acts on immune cells → immune activation exacerbates symptoms.

Microbiota-Gut-Brain Axis
- Chronic stress alters gut flora.
- Dysbiosis contributes to altered immunity, neuroendocrine signaling & GI symptoms

Question 4

Evidence highlights:
- clinical evidence
- animal models

Answer 4

Clinical Evidence
- 40–80% of IBS patients have psychiatric comorbidities (depression, anxiety).
- Early adverse life events (EALs) correlate with IBS onset and severity.
- Stressful life events often precede IBS symptoms.

Animal Models
- Neonatal maternal separation and water avoidance stress induce IBS-like changes.
- CRF triggers mast cell activity and changes in gut permeability.
- Serotonin (5-HT) pathways are altered, leading to pain, altered motility, and secretion

Question 5

Top-down vs bottom-up models

Answer 5

Table

Question 6

Treatment strategies:
- non pharmaco
- pharmaco

Answer 6

Non-Pharmacological
- CBT, hypnosis, stress management
- Dietary changes (ex: probiotics)
- Exercise & patient education
- Biofeedback therapy

Pharmacological
- Antidepressants, antipsychotics
- Targeting 5-HT system:
o 5-HT synthesis inhibitors (ex: LX1031)
o 5-HT3 antagonists (ex: alosetron)
o 5-HT4 agonists (ex: prucalopride)
- Consider risk-benefit (ex: adverse effects of alosetron & tegaserod