Serum and colonic mucosal immune markers in irritable bowel syndrome.

OBJECTIVES: Low-grade colonic mucosal inflammation has been postulated to have an important role in the pathophysiology of irritable bowel syndrome (IBS). The objectives of this study were (i) to identify serum and tissue-based immunological and neuroendocrine markers associated with mucosal inflammation in male (M) and female (F) patients with non-post-infectious IBS (non-PI-IBS) compared with healthy controls and (ii) to assess possible correlations of such markers with IBS symptoms. METHODS: Sigmoid mucosal biopsies were obtained from 45 Rome II positive IBS patients without a history of PI-IBS (26 F, 35.5% IBS-C, 33.3% IBS-D, 31.1% IBS-A/M) and 41 healthy controls (22 F) in order to measure immunological markers (serum cytokine levels, colonic mucosal mRNA levels of cytokines, mucosal immune cell counts) and neuroendocrine markers associated with mucosal inflammation (corticotropin releasing factor- and neurokinin (NK)-related ligands and receptors, enterochromaffin cells). Symptoms were measured using validated questionnaires. RESULTS: Of all the serum and mucosal cytokines measured, only interleukin-10 (IL-10) mRNA expression showed a group difference, with female, but not male, patients showing lower levels compared with female controls (18.0±2.9 vs. 29.5±4.0, P=0.006). Mucosal mRNA expression of NK-1 receptor was significantly lower (1.15±0.19 vs. 2.66±0.56, P=0.008) in female, but not male, patients compared with healthy controls. No other significant differences were observed. CONCLUSIONS: Immune cell counts and levels of cytokines and neuropeptides that are associated with inflammation were not significantly elevated in the colonic mucosa of non-PI-IBS patients, and did not correlate with symptoms. Thus, these findings do not support that colonic mucosal inflammation consistently has a primary role in these patients. However, the finding of decreased IL-10 mRNA expression may be a possible biomarker of IBS and warrants further investigation.

Childhood trauma is associated with hypothalamic-pituitary-adrenal axis responsiveness in irritable bowel syndrome.

BACKGROUND & AIMS: A history of early adverse life events (EALs) is associated with a poorer outcome and higher levels of distress in adult patients with functional gastrointestinal disorders. An EAL is thought to predispose individuals to develop a range of chronic illnesses by inducing persistent changes in the central stress response systems, including the hypothalamic-pituitary-adrenal (HPA) axis. We sought to determine if EALs affect the HPA axis response to a visceral stressor in irritable bowel syndrome (IBS) patients and healthy controls, and to determine if this is affected by sex or related to symptoms or quality of life. METHODS: Forty-four IBS patients (25 women, 19 men) and 39 healthy controls (21 women, 18 men) were assessed for gastrointestinal and psychological symptoms and EALs by validated questionnaires and interview. All subjects underwent a visceral stressor (sigmoidoscopy). Salivary cortisol was collected at baseline and serially for 1 hour poststressor. RESULTS: Twenty-one IBS patients and 18 controls had EALs. In subjects with and without IBS, an EAL was associated with higher mean (+/-SD) cortisol levels (0.32 +/- 0.2 vs 0.20 +/- 0.1 microg/dL; P = .003) and higher area under the curve (28.1 +/- 17 vs 18.6 +/- 13 microg x min/dL; P = .005) after the stressor compared with subjects without EALs. In IBS, a faster resolution of cortisol to basal values corresponded to lower symptom severity (r = -0.36, P < .05) and better disease-specific quality of life (r = 0.33, P < .05). CONCLUSIONS: HPA axis hyperresponsiveness to a visceral stressor is related more to a history of EALs than to the presence of IBS. However, HPA axis reactivity has a moderating effect on IBS symptoms.

The effect of life stress on symptoms of heartburn.

OBJECTIVE: Psychosocial stressors have been associated with exacerbations of symptoms in functional and inflammatory disorders of the gastrointestinal tract. The present longitudinal study tests the general hypothesis that life stressors can exacerbate symptoms in patients with chronic heartburn. METHODS: Sixty subjects with current heartburn symptoms were recruited by community advertisement and assessed for presence of stressful life events retrospectively over the preceding 6 months and prospectively for 4 months. Symptom severity by daily diary, quality of life, and psychological symptoms of anxiety, depression, and vital exhaustion were also measured. RESULTS: The presence of a severe, sustained life stress during the previous 6 months significantly predicted increased heartburn symptoms during the following 4 months. In addition, symptoms showed a strong, independent correlation with vital exhaustion. Affective and subjective stress ratings were not strongly related to heartburn severity; however, anxiety showed the strongest relationship to impaired quality of life and depression to heartburn medication use. CONCLUSIONS: As with other chronic conditions such as irritable bowel syndrome (IBS), heartburn severity appears to be most responsive to major life events and not an accumulation of more minor stressors or fluctuations in mood. In addition, vital exhaustion, which may in part result from sustained stress, may represent the psychophysiological symptom complex most closely associated with heartburn exacerbation. Potential mechanisms for these results include increased level and frequency of esophageal acid exposure, inhibition of gastric emptying of acid, or stress-induced hypersensitivity.

Irritable bowel syndrome patients show enhanced modulation of visceral perception by auditory stress.

OBJECTIVES: Symptoms in irritable bowel syndrome (IBS) patients are sensitive to psychological stressors. These effects may operate through an enhanced responsiveness of the emotional motor system, a network of brain circuits that modulate arousal, viscerosomatic perception, and autonomic responses associated with emotional responses, including anxiety and anger. The aim of this study was to test the primary hypothesis that IBS patients show altered perceptual responses to rectal balloon distention during experimentally induced psychological stress compared with healthy control subjects. METHODS: A total of 15 IBS patients (nine women and six men) and 14 healthy controls (seven women and seven men) were studied during two laboratory sessions: 1) a mild stress condition (dichotomous listening to two conflicting types of music), and 2) a control condition (relaxing nature sounds). The stress and relaxation auditory stimuli were delivered over a 10-min listening period preceding rectal distentions and during the rectal distentions but not during the distention rating process. Ratings of intensity and unpleasantness of the visceral sensations, subjective emotional responses, heart rate, and neuroendocrine measures (norepinephrine, cortisol, adrenocorticotropic hormone [ACTH], and prolactin) were obtained during the study. RESULTS: IBS patients, but not healthy controls, rated the 45-mm Hg visceral stimulus significantly higher in terms of intensity and unpleasantness during the stress condition compared with the relaxation condition. IBS patients also reported higher ratings of stress, anger, and anxiety during the stress compared with the relaxing condition, whereas controls had smaller and nonsignificant subjective responses. Heart rate measurements, but not other neuroendocrine stress measures, were increased under the stress condition in both groups. CONCLUSION: These findings confirm the hypothesis of altered stress-induced modulation of visceral perception in IBS patients.