STRESS AND THE GUT(7)

were reported to modulate the activity of serotonin in the gut.Serotonin stored in enterochromaffin cells (ECC) plays a crucialrole in the motility, visceral sensitivity and secretion. Furtherdrugs effective in IBS treatment include antimuscarinic agents,µ-opioid antagonists, CRF antagonists, chloride channel openerand even melatonin (50). This last group of drugs show apositive effect on IBS anti-motility effects. Melatonin strongly prevents theviaantioxidative, anti-inflammatory andexacerbation of colitis caused by stress as shown in appropriateanimal models (51).

Treatment options for IBS with the predominant symptom beingPharmacotherapy should be based on the leading symptoms.diarrhoea (IBD-D) include anti-diarrhoeals such as loperamide (1-8 mg for times daily in divided doses). It is important to titratedose for desired effect to side effects such as constipation.Although loperamide is useful for the treatment of diarrhoea, noglobal symptom relief can be expected under this medication (51).Interestingly, the 5-HTtwice daily have been shown to be effective in the treatment of3-antagonists such as alosetron 0.5-1 mgdiarrhoea in IBS patients. However, the serious complications,especially ischemic colitis limited its use and led to the withdrawalof this medication from the market in Germany. However, in theUSAwomen under an appropriate risk management program (52, 53).alosetron is available for the treatment of severe IBS-D inRecently, Pimentel antibiotic rifaximin showed a global efficacy and significantet al.(54) demonstrated that luminal actingimprovement of bloating in IBS-D patients. Moreover, tricyclicantidepressant (amitryptiline 10-150 mg at night; doxepin 10-130mg at night, trimipramine 10-150 mg at night or desipramine 10-150 mg at night patients. It is important to initiate the therapy at a lower dose thanetc.) can be recommended in some IBS-Dthe typical dose given for mood disorders (48). Finally, recentstudies indicate that some probiotics may be useful in the therapyof diarrhoea in IBS patients. However, the exact dose of probioticsrequires evaluation with more number of studies (48).

include the bulking agents (psyllium 2.5-30 g daily in dividedTreatment options for IBS patients with constipation (IBS-C)doses) and laxatives (polyethylene glycol, PEG) (55, 56).Prucalopride, which is a selective 5-HTonce daily, relieved symptoms of constipation in patients with4agonist given 1-2 mgIBS-C (57). The activators of mucosal epithelial chloridechannels play an important role in fluid transportation within thecolon and may be successfully implemented in the therapy of IBSpatients with constipation. Lubiprostone, with an approved IBS-C patients dose of 8 µg twice daily is a prostaglandin Ederivative which activates the mucosal epithelial chloride1channels and promotes chloride-rich fluid secretion into thelumen of GI tract. This leads to softening of the stool andacceleration of colonic transit (58). Finally, there is also evidencethat some probiotic strains may be useful in IBS-C patients (59).

line of therapy is a antispasmodics such as hyoscamine sulphateIn IBS patients with bloating and pain the recommended first(0.125 up to four times daily) or dicyclomine (10-10 mg twicedaily up to four times daily). Antispasmodics act predominantlyas antagonists at cholinergic receptors and thereby reducecontraction of the GI tract. In addition to reduction of coloniccontraction by antispasmodics, tricyclic antidepressants (TCA)and selective serotonin reuptake inhibitors SSRI such asfluoxetine (10-40 mg daily), citalopram (20 mg daily), sertraline(25-100 mg daily) and escitalopram (10 mg daily) are effectivein the treatment of chronic pain in IBS patients. At the molecularlevel, TCAnorepinephrine, increasing the bioavailability of theseinhibit the re-uptake of both serotonin andneurotransmitters in the synaptic cleft. In contrast, SSRI preventthe re-uptake of serotonin alone (60). In recent years alpha 2delta (α2δ) ligands, gabapentin and pregabalin have been shown597

pre- and probiotics may positively influence the visceralhypersensitivity and reduce bloating in IBS patients. However,the clinical benefits seem to be strain-dependent (62).

positive effect of probiotics IBS on symptoms. The postulatedRecently, an increasing number of studies indicates themechanisms of action of probiotics on stressed gastrointestinalmucosa include: 1) improvement of the barrier function of theepithelium (permeability); 2) suppression of the growth andbinding of pathogenic bacteria; 3) positive effect on visceralhypersensitivity and 4) immunomodulatory effect (inhibition ofsubclinical inflammation in IBS). Despite the high number ofstudies using probiotics in IBS patients, a lot of new questionshave been left unanswered such as the optimal dose, its role incombination therapy, strain specific activity, stability within GItract, possible development of antibiotic resistance and theduration of therapy. Probiotics may vary in species, strains,preparation and doses, what makes the interpretation of theefficacy difficult. To answer all these questions, large placebo-controlled trials are needed in the future.

could be recommended. However, a physician combiningIn some clinical settings, a combination therapy approachdifferent types of drugs should be aware of possible side effectsand interactions. Combination therapy should be aimed at thepredominant symptoms of the patient (63).

behavioural therapy (CBT), dynamic psychotherapy, stressComplementary or alternative approaches includes cognitivemanagement, hypnotherapy, relaxation therapy and evenacupuncture represent further important treatment approaches toreduce the symptoms of IBS (64, 65). These forms of therapyshould not only be used in refractory forms of disease, but alsoused as useful adjunctive therapy.

CONCLUSIONS

stress) is a major risk factor in the pathogenesis of differentWe conclude that 1) exposure to stress (especially chronicdiseases of gastrointestinal tract including gastroesophagealreflux disease (GERD), peptic ulcer, functional dyspepsia,inflammatory bowel disease (IBD), irritable bowel disease (IBS),and other functional disorders of GI tract; 2) the dysregulation ofbrain-gut-axis plays a central role in the pathogenesis of stress-induced diseases; 3) Stress increases intestinal permeability,visceral sensitivity, alteration in GI-motility and leads toprofound mast cell activation resulting in release of manyproinflammatory mediators; 4) diagnostic approach to stress-induced gastrointestinal disorders includes: laboratory tests,imaging techniques (abdominal sonography), endoscopy(gastroscopy, colonoscopy, small intestine endoscopy) as well asHovergrowth (SIBO) and maldigestion of carbohydrates; 5)2breath test for exclusion of small intestinal bacterialTherapy is based mainly on the leading symptoms and includesgeneral measurements, pharmacotherapy as well aspsychological and behavioural therapies.

Conflict of interests: None declared.

REFERENCES

1.Selye H. Syndrome produced by diverse nocuous agents.

2.NatureBhatia V1936; 138: 32.

3.J Gastroenterol Hepatol, Tandon RK. Stress and the gastrointestinal tract.

Soderholm JD, Perdue MH. Stress and gastrointestinal tract.

2005; 20: 332-339.

II. Stress and intestinal barrier function. Am J Physiol

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