A combined nutrient and lactulose challenge test allows symptom-based clustering of patients with irritable bowel syndrome.

OBJECTIVES: The aim of the present pilot study was to evaluate the usefulness of a test meal containing lactulose in the non-invasive assessment of visceral sensitivity in irritable bowel syndrome (IBS), and to identify subsets of IBS patients based on gastrointestinal (GI) symptom generation. METHODS: We included 43 patients with IBS (Rome III) and 29 healthy controls. The fasted subjects were served three test meals consisting of a 400-ml liquid breakfast alone or containing lactulose (15 or 25 g) in a double-blind crossover design. Seven GI symptoms, overall digestive comfort, and exhaled H2/CH4 were assessed at baseline and every 15 min during 4 h after meal intake. Anxiety and depression were assessed only at baseline. A mapping of the seven GI symptoms was done using a Principal Component Analysis (4 h mean area under the curve, AUC). Independently, a hierarchical cluster analysis was performed on the same parameters to identify GI symptom-based IBS clusters. RESULTS: All three tests were well tolerated. The 25 g lactulose challenge enabled discrimination of IBS from healthy controls according to the symptom response. This challenge also enabled clustering of IBS subjects in two subgroups based mainly on bloating, distension, and discomfort symptoms (2,457 (2,043-2,872), 2,450 (1,910-2,990), 2,602 (2,126-3,079) vs. 537 (383-691), 619 (458-780), 643 (432-854); 4 h mean AUC; P<0.0001), overall digestive comfort (1807 (1318-2295) vs. 3350 (2942-3758); 4 h mean AUC; P<0.0001), and anxiety at baseline (9.2 (7.0-11.5) vs. 5.5 (4.2-6.9); Hospital Anxiety and Depression scale anxiety mean scores; P=0.003). This clustering was independent of the Rome III subtype and the amount of exhaled H2/CH4. CONCLUSIONS: The lactulose challenge test seems to be a promising tool to assess visceral sensitivity in IBS, and to subgroup IBS patients based on their symptom pattern.

Randomised clinical trial: symptoms of the irritable bowel syndrome are improved by a psycho-education group intervention.

BACKGROUND: Evidence supports the effectiveness of cognitive behavioural approaches in improving the symptoms of the irritable bowel syndrome (IBS). Duration, cost and resistance of many patients towards a psychological therapy have limited their acceptance. AIM: To evaluate the effectiveness of a psycho-educational intervention on IBS symptoms. METHODS: Sixty-nine IBS patients (72% female) were randomised to an intervention or a wait-list control group. The IBS class consisted of education on a biological mind body disease model emphasising self-efficacy and practical relaxation techniques. RESULTS: Patients in the intervention showed significant improvement on GI symptom severity, visceral sensitivity, depression and QoL postintervention and most of these gains were maintained at 3-month follow-up (Hedge's g = -0.46-0.77). Moderated mediation analyses indicated change in anxiety, visceral sensitivity, QoL and catastrophising due to the intervention had moderate mediation effects (Hedge's g = -0.38 to -0.60) on improvements in GI symptom severity for patients entering the trial with low to average QoL. Also, change in GI symptom severity due to the intervention had moderate mediation effects on improvements in QoL especially in patients with low to average levels of QoL at baseline. Moderated mediation analyses indicated mediation was less effective for patients entering the intervention with high QoL. CONCLUSIONS: A brief psycho-educational group intervention is efficacious in changing cognitions and fears about the symptoms of the irritable bowel syndrome, and these changes are associated with clinically meaningful improvement in symptoms and quality of life. The intervention seems particularly tailored to patients with low to moderate quality of life baseline levels.

Clinical trial: the effects of a fermented milk containing three probiotic bacteria in patients with irritable bowel syndrome - a randomized, double-blind, controlled study.

BACKGROUND: The effects of probiotic bacteria in IBS remain controversial. AIM: To study the effects of a probiotic product on IBS symptoms. METHODS: We randomized 74 IBS patients to receive 8 weeks of daily treatment with 400 mL milk fermented with the yoghurt bacteria and containing Lactobacillus paracasei, ssp. paracasei F19, Lactobacillus acidophilus La5 and Bifidobacterium lactis Bb12 (Cultura; active) or acidified milk without these bacteria (control). The primary endpoint was the proportion of subjects reporting adequate relief of their IBS symptoms at least 50% of the weeks. IBS symptom severity, psychological symptoms and quality of life were assessed. RESULTS: The proportion of responders was 38% (14/37 patients) in the active group and 27% (10/37 patients) in the control group (P = 0.3). IBS symptom severity improved significantly in both groups during the treatment period. This change was greater in the active group during the first 2 weeks, but thereafter, no significant group differences were seen. CONCLUSIONS: We could not detect a clearly positive effect of fermented milk containing three probiotic bacteria on GI symptoms in IBS patients compared with the control treatment. However, a trend towards a more favourable effect during the first weeks was seen in the active group.

B-cell activation in patients with irritable bowel syndrome (IBS).

Patients with irritable bowel syndrome (IBS) may have a low grade immune activation. However, little is known about the properties of B cells of IBS patients. We therefore investigated activation level and antigen presenting phenotype of blood B cells of IBS patients. We also examined B-cell responses to lipopolysaccharide (LPS) and probiotic bacteria. Blood samples were obtained from 74 IBS patients and 30 healthy subjects. Peripheral blood mononuclear cells were isolated and stimulated with LPS or an UV-light inactivated bacterial cocktail consisting of the probiotic Gram-positive strains; Lactobacillus paracasei ssp. paracasei 19, Lactobacillus acidophilus La5, Bifidobacterium lactis B612. The phenotype of CD19(+) B cells was investigated by flow cytometry before and after 72 h cell culture. Furthermore, IBS symptom severity was assessed. B cells isolated from blood of IBS patients displayed an amplified activation level as demonstrated by increased cell surface expression of IgG, and also the costimulatory molecules CD80 and CD86. Expression of antigen presenting HLA-DR and costimulatory molecule CD40 on B cells was, however comparable in IBS patients and controls. B cells of IBS patients displayed an impaired ability to increase expression of CD80, but not CD86, in response to both LPS as well as probiotic bacteria stimulations. To conclude, blood B cells of IBS patients have an increased activation level. Bacterial component induced expression of the costimulatory molecule CD80, regarded as important for tolerance induction, is impaired. These data suggest that B-cell antigen presentation in IBS patients is associated with altered capacity of providing costimulation to T cells.

Predictors of subjective fatigue in chronic gastrointestinal disease.

BACKGROUND: Fatigue is a common, but poorly understood symptom in patients with chronic gastrointestinal (GI) diseases. AIM: To evaluate factors of importance for fatigue in patients with chronic GI diseases, and to compare it with fatigue in the general population. METHODS: In all, 399 patients attending a GI out-patient clinic completed questionnaires assessing fatigue, sleep disturbances, psychological general well-being and GI symptom severity. The patients were divided into two diagnostic groups: functional GI disorders (n = 112) and organic GI diseases (n = 287). The severity of fatigue was also evaluated in an age- and gender-matched group of 399 individuals from the general population. RESULTS: Both patient groups had more severe fatigue than controls and patients with functional GI disorders were more fatigued than patients with an organic GI disease. Fatigue was associated with psychological general well-being, GI symptom severity, gender, employment status and sleep disturbances. In a linear regression analysis, psychological general well-being (vitality, general health, self-control), sleep disturbances and employment status were independently associated with the severity of fatigue (adjusted R(2) = 55%). CONCLUSIONS: Fatigue is a troublesome symptom in a subgroup of patients with chronic GI diseases. These patients have a high symptom burden as regards both GI and psychological symptoms, as well as sleep disturbances.

Subtyping the irritable bowel syndrome by predominant bowel habit: Rome II versus Rome III.

BACKGROUND: The agreement between subtyping irritable bowel syndrome (IBS) patients based on Rome II criteria versus Rome III criteria is unknown. AIM: To compare IBS subtyping based on Rome II versus III criteria. METHODS: The Rome II Modular Questionnaire and the Bristol Stool Form Scale (one-week diary cards) were completed by 249 IBS patients. Based on the Rome II criteria, patients were defined as having diarrhoea- or constipation-predominant IBS, or alternating IBS. Based on the Rome III criteria, patients were divided into IBS with constipation, IBS with diarrhoea, mixed IBS or unsubtyped IBS. Agreement between Rome II and Rome III was assessed with kappa statistics. RESULTS: Based on Rome II there were 92 diarrhoea-predominant IBS, 45 constipation-predominant IBS and 112 alternating IBS, and based on Rome III 97 IBS with diarrhoea, 77 IBS with constipation, 16 mixed IBS and 59 unsubtyped IBS. The agreement between Rome II and Rome III subgroups was 46% (kappa = 0.19). Changes from the constipation to the diarrhoea subgroups and vice versa were uncommon (8% of patients). The majority of changes occurred from/to the alternating IBS, mixed IBS and unsubtyped IBS subgroups. CONCLUSION: There is poor agreement between subtyping of IBS patients based on Rome II versus Rome III criteria.

Altered visceral perceptual and neuroendocrine response in patients with irritable bowel syndrome during mental stress.

BACKGROUND AND AIMS: Stress often worsens the symptoms of irritable bowel syndrome (IBS). We hypothesised that this might be explained by altered neuroendocrine and visceral sensory responses to stress in IBS patients. SUBJECTS AND METHODS: Eighteen IBS patients and 22 control subjects were assessed using rectal balloon distensions before, during, and after mental stress. Ten controls and nine patients were studied in supplementary sessions. Rectal sensitivity (thresholds and intensity-visual analogue scale (VAS)) and perceived stress and arousal (VAS) were determined. Plasma levels of corticotropin releasing factor (CRF), adrenocorticotropic hormone (ACTH), cortisol, noradrenaline, and adrenaline were analysed at baseline, immediately after stress, and after the last distension. Heart rate was recorded continuously. RESULTS: Thresholds were increased during stress in control subjects (p<0.01) but not in IBS patients. Both groups showed lower thresholds after stress (p<0.05). Repeated distensions without stress did not affect thresholds. Both groups showed increased heart rate (p<0.001) and VAS ratings for stress and arousal (p<0.05) during stress. Patients demonstrated higher ratings for stress but lower for arousal than controls. Basal CRF levels were lower in patients (p<0.05) and increased significantly during stress in patients (p<0.01) but not in controls. Patients also responded with higher levels of ACTH during stress (p<0.05) and had higher basal levels of noradrenaline than controls (p<0.01). Controls, but not patients, showed increased levels of adrenaline and noradrenaline in response to stress (p<0.05). CONCLUSIONS: Stress induced exaggeration of the neuroendocrine response and visceral perceptual alterations during and after stress may explain some of the stress related gastrointestinal symptoms in IBS.