STRESS AND THE GUT(4)

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the strong impact of acute stress such as terroristic attack onWorld Trade Center on GERD symptoms.

Exposure to a stressful life events may evoke thedevelopment of PUD. Ulcer patients are more likely to bedivorced, separated or widowed. Despite the fact thatHelicobacter pylori(Hp) and nonsteroidal anti-inflammatorydrugs (NSAID) are the important causes of PUD, it has beenshown that stress exposure may contribute to this disease andmay impede the gastric and duodenal defences against thedamage induced by an attack from acid and pepsin damage (26).Possible causative factors include: 1) alterations in gastric acidsecretion; 2) reduced mucosal blood flow; 3) reduced HCO3-secretion; 4) acid back diffusion; 5) reduced proliferation andrestitution of the injured mucosa; 6) alterations in gastricmotility. Before the discovery of Hp, stress was considered asone of the most important risk factor for peptic ulceration (27).Aspecial form of ulcerations resulting from intense stressexposure is termed as a stress ulceration, commonly observed inpatients in intensive care units (28).

Our own studies demonstrated that stress may profoundlyaffect the BGAviathe modulation of a number of importantneuropeptides (like CGRP) involved in the protection of thegastric mucosa, changes in gastric secretion, regeneration ofgastric mucosa, and changes in mucosal blood flow (29-30)(Fig. 4).

From a practical point of view, the diagnostic approach tostress-related diseases in the upper GI tract includes non-invasive and invasive techniques (31). Non-invasive techniquesconsist of 1) routine blood tests (complete blood count,chemistries, thyroid function, stool diagnostic); 2) celiac diseaseserology (transglutaminase IgA), 13C urease breath test toexclude Hp infection, determination of elastase-1 in stool toexclude exocrine pancreatic insufficiency, H2breath test withglucose to exclude small intestinal bacterial overgrowth (SIBO),H2breath testing to rule out carbohydrate malabsorption,abdominal ultrasonography and other imaging methods (MRI),sucrose permeability test to analyze the intestinal barrierfunction and evaluation of the gut motility with H2breath testusing lactulose. The invasive techniques include upper GI tractendoscopy or intestinal endoscopy (capsule endoscopy, push-and pull enteroscopy).

Therapies of stress-related disorders within the upper GItract are focused mainly on the inhibition of gastric acidsecretion using proton pump inhibitors (PPI), histamine-H2

blockers, etc.In the case of Hp infection, an appropriateeradication should be advocated, because the eradication of Hpmay lead in some patients with functional dyspepsia and animprovement of the symptoms (32, 33). Recently, some studiesindicate a positive effect of probiotics on stress related pathologyin upper GI tract, however the effects need to be furtherevaluated (34).

Stress is also a known risk factor for the induction andexacerbation of IBD. There is evidence that stress may induce denovocolitis or provokes the exacerbation of colitis (35).However, not all studies support this association, so more largeprospective population-based studies are needed to betterexplore these potential interaction. Additionally, animal modelsare another line of evidence (36). Numerous studies havedemonstrated that stress may aggravate the experimental colitisby increasing oxidative damage (37). Finally, human studiesrevealed a close association between acute daily stressors andvarious bowel symptoms (38). The exact mechanisms by whichstress exposure may induce or aggravate colitis is not wellknown, but probably by activation of mast cells, increasedrelease of cells and impairment of the intestinal barrier function(20) (Fig. 5).

There is also evidence that stress may have a profoundeffect on bacterial flora leading to increased adhesion andtranslocation of bacteria due to increased barrier permeability.This may be an important factor leading to the activation of theimmune system resulting in the exacerbation or induction ofacute colitis (39). Importantly, this effect could be alleviated byprobiotics or antibiotics.

IRRITABLE BOWELSYNDROME AS THE IMPORTANT

MANIFESTATION OF STRESS IN LOWER

GASTROINTESTINALTRACTOne of the most important diseases of the GI tract that islinked to stress exposure to gut is IBS, which represents acommon, but heterogeneous gastrointestinal disorder with aworldwide prevalence of between 10-20%. Females are morecommonly involved than males (F:M; 2:1 ratio). IBS is afunctional disease and its diagnosis is mainly based on theexclusion of organic disease. IBS is characterized by periods offlare-ups and periods of remission. The most common symptomsare diarrhoea, constipation, abdominal pain and bloating (40-41).

Fig. 4. Effect of disruption ofbrain-gut axis on ulcerhealing. Exposure to stressand the resulting disturbanceof brain-gut axis may havenegative effect on ulcerhealing including changes ingastric secretion, proliferationrate at the ulcer edge and

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