Response In Irritable Bowel Syndrome Research Articles

Predictors of Symptom-Specific Treatment Response to Dietary Interventions in Irritable Bowel Syndrome.

(1) Background: Predictors of dietary treatment response in irritable bowel syndrome (IBS) remain understudied. We aimed to investigate predictors of symptom improvement during the low FODMAP and the traditional IBS diet for four weeks. (2) Methods: Baseline measures included faecal Dysbiosis Index, food diaries with daily energy and FODMAP intake, non-gastrointestinal (GI) somatic symptoms, GI-specific anxiety, and psychological distress. Outcomes were bloating, constipation, diarrhea, and pain symptom scores treated as continuous variables in linear mixed models. (3) Results: We included 33 and 34 patients on the low FODMAP and traditional IBS diet, respectively. Less severe dysbiosis and higher energy intake predicted better pain response to both diets. Less severe dysbiosis also predicted better constipation response to both diets. More severe psychological distress predicted worse bloating response to both diets. For the different outcomes, several differential predictors were identified, indicating that baseline factors could predict better improvement in one treatment arm, but worse improvement in the other treatment arm. (4) Conclusions: Psychological, nutritional, and microbial factors predict symptom improvement when following the low FODMAP and traditional IBS diet. Findings may help individualize dietary treatment in IBS.

Smart Data Collection for the Assessment of Treatment Effects in Irritable Bowel Syndrome: Observational Study.

BackgroundEnd-of-day symptom diaries are recommended by drug regulatory authorities to assess treatment response in patients with irritable bowel syndrome. We developed a smartphone app to measure treatment response.ObjectiveBecause the employment of an app to measure treatment response in irritable bowel syndrome is relatively new, we aimed to explore patients’ adherence to diary use and characteristics associated with adherence.MethodsA smartphone app was developed to serve as a symptom diary. Patients with irritable bowel syndrome (based on Rome IV criteria) were instructed to fill out end-of-day diary questionnaires during an 8-week treatment. Additional online questionnaires assessed demographics, irritable bowel syndrome symptom severity, and psychosocial comorbidities. Adherence rate to the diary was defined as the percentage of days completed out of total days. Adherence to the additional web-based questionnaires was also assessed.ResultsOverall, 189 patients were included (age: mean 34.0 years, SD 13.3 years; female: 147/189, 77.8%; male: 42/189, 22.2%). The mean adherence rate was 87.9% (SD 9.4%). However, adherence to the diary decreased over time (P<.001). No significant association was found between adherence and gender (P=.84), age (P=.22), or education level (lower education level: P=.58, middle education level: P=.46, versus high education level), while higher anxiety scores were associated with lower adherence (P=.03). Adherence to the online questionnaires was also high (>99%). Missing data due to technical issues were limited.ConclusionsThe use of a smartphone app as a symptom diary to assess treatment response resulted in high patient adherence. The data-collection framework described led to standardized data collection with excellent completeness and can be used for future randomized controlled trials. Due to the slight decrease in adherence to diary use throughout the study, this method might be less suitable for longer trials.

Su1606 – Autonomic Nervous System Response in Irritable Bowel Syndrome is Associated with Sex, Bowel Habit and Gut Microbiota

Su1606 – Autonomic Nervous System Response in Irritable Bowel Syndrome is Associated with Sex, Bowel Habit and Gut Microbiota

Clinical response to linaclotide at week 4 predicts sustained response in irritable bowel syndrome with constipation and improvements in digestive and extra-digestive symptoms.

Background:Linaclotide is approved for the treatment of moderate-to-severe irritable bowel syndrome (IBS) with constipation (IBS-C) in adults. This study aimed to assess factors predictive of a clinical response and improvements in non-IBS symptoms with linaclotide treatment in a Spanish patient population.Methods:In this open-label phase IIIb study, patients with moderate-to-severe IBS-C received linaclotide 290 μg once daily for 12 weeks. The primary endpoint was clinical response at week 12, defined as >30% reduction in IBS symptom severity score (IBS-SSS) or IBS-SSS <75 plus self-reported response of feeling ‘better’ or ‘much better’ versus the baseline. Digestive nonintestinal and extra-digestive symptom scores were assessed. Baseline characteristics and week 4 clinical response were assessed as predictors of week 12 clinical response.Results:A total of 96 patients were eligible; 91 were female and the mean age was 47.4 years. Mean (SD) baseline IBS-SSS was 371 (72.5). In the intention-to-treat and per-protocol populations, 22.9% and 31.7% were clinical responders at week 4, respectively, and 25.0% and 36.7% were clinical responders at week 12. Digestive nonintestinal and extra-digestive symptom scores were significantly improved at weeks 4 and 12. Baseline characteristic was not associated with week 12 clinical response; however, clinical response at week 4 was predictive of response at week 12 (OR: 6.5; 95%IC: 2.1–19.8). The most common adverse event was diarrhea inclusive of loose or watery stools (35.4%).Conclusions:Linaclotide improves IBS-C symptoms, including digestive nonintestinal and extra-digestive symptoms. A clinical response at week 4 may predict response at week 12.

Modulation of inflammation by toll-like receptor 4/nuclear factor-kappa B in diarrhea-predominant irritable bowel syndrome.

In order to investigate the function of toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signal pathways in the pathogenesis of diarrhea-predominant irritable bowel syndrome (IBS-D), IBS-D animal models were established in wistar rats challenged with acute and chronic stresses (29 days). Wistar rats without stress-challenged were used as controls. IBS-D models were randomly divided into two groups: one was treated with normal saline, another group was treated with TLR4/NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC) (50mg/kg/week) for continuous four times. Our results demonstrate that continuous stresses can induce the characteristic symptoms of IBS-D, including high wet stool rate and intestinal flora imbalance. Further examinations of colon tissues show that the protein expression levels of TLR4 and NF-κB in IBS-D groups are higher than that in control group. The secretory levels of interleukin (IL-8), tumor necrosis factor α (TNFα), and myeloid differentiation factor 88 (MyD88) are significantly increased in IBS-D group. Administration with PDTC effectively downregulates levels of these inflammatory factors. In contrast, interleukin-10 (IL-10) is in an opposite alteration with lower levels in IBS-D groups and the PDTC treatment increases it to the levels as in control group. Moreover, inhibition of the TLR4/NF-κB by PDTC improves the microstructure of intestinal mucosa mainly by increasing the height of villi. Our results suggest that TLR4/NF-κB signal pathway plays an important role in the modulation of inflammatory responses in IBS-D, which might be a therapeutic target for the IBS-D. All of these findings also provide the evidence concerning an inherent linkage between the axis of stress/NF-κB/inflammation and IBS-D.

Immune response in irritable bowel syndrome: A systematic review of systemic and mucosal inflammatory mediators.

To systematically review the available data on cytokine and immune cells in the peripheral blood and mucosal biopsy samples from patients with irritable bowel syndrome (IBS). From a review of the literature, data on cytokines and immune cells that had been assayed in at least three independent studies were collated and trends examined. Levels of interleukin (IL)-10 tended to be decreased and those of IL-6, IL-8, tumor necrosis factor-α and IL-1β increased in the systemic circulation in IBS, while in the mucosa, IL-10 was decreased and IL-8, mast cells, enterochromaffin cells and CD3+ T lymphocytes were increased. However, these findings were not consistent across all studies and, in some instances, were limited to certain IBS sub-populations. The interpretation of this literature is limited by several factors, such as the intrinsic heterogeneity of IBS and a lack of standardization in study design. While a number of intriguing immunological observations have been made in IBS, more work is needed before a compelling case can be made for a role for immune-mediated events in the etiology of IBS.

244 Enhanced Stimulated Stress Hormone Response in Irritable Bowel Syndrome (IBS) Is Associated With Downregulation of Glucocorticoid Receptor Expression

244 Enhanced Stimulated Stress Hormone Response in Irritable Bowel Syndrome (IBS) Is Associated With Downregulation of Glucocorticoid Receptor Expression

Autonomic response to a visceral stressor is dysregulated in irritable bowel syndrome and correlates with duration of disease

Previous studies reported altered autonomic nervous system (ANS) responses in irritable bowel syndrome (IBS) at baseline and to colonic balloon distension. This study examined heart rate variability (HRV) and plasma catecholamines as an index of ANS responsiveness in IBS during flexible sigmoidoscopy (FS) and explored associations of HRV with clinical measures. Rome III-positive IBS patients and healthy controls completed questionnaires measuring gastrointestinal and psychological symptoms. Heart rate variability measures were calculated using electrocardiogram (ECG) data at rest and during FS. Plasma catecholamines were measured before and after the FS. Linear mixed effects models were used to compare HRV with IBS status and IBS duration across six time points. Significance was assessed at the 0.05 level. Thirty-six IBS patients (53% F, mean age 37.89) and 31 controls (58% F, mean age 37.26) participated. After adjusting for age, sex, body mass index, and current anxiety symptoms, IBS patients had a non-significant lower cardiovagal tone (P=0.436) and higher cardiosympathetic balance (P=0.316) at rest. During FS, controls showed a transient increase in cardiosympathetic balance and decrease in cardiovagal tone. However, IBS patients had significantly less cardiosympathetic and cardiovagal responsiveness both leading up to (P=0.003, P=0.005) and following (P=0.001) this stimulus. Those with longer duration of disease had less cardiosympathetic (P=0.014) and cardiovagal (P=0.009) responsiveness than those with shorter duration. No differences in catecholamines between IBS and controls were found. Irritable bowel syndrome demonstrated dysregulated ANS responses to a visceral stressor which could be related to disease duration. Therefore, autonomic dysregulation is an objective physiologic correlate of IBS.

Genetic biomarkers of placebo response: what could it mean for future trial design?

Genetic biomarkers of placebo response: what could it mean for future trial design?

Evidence of an enhanced central 5HT response in irritable bowel syndrome and in the rat maternal separation model

Efforts to define either a biomarker for irritable bowel syndrome (IBS) or a valid animal model have proven disappointing. The aims of this study were to determine if buspirone stimulates prolactin release through the 5-hydroxytryptamine (5HT)1a receptor and whether this response is altered in patients with IBS and in the rat maternal separation model. Buspirone (30 mg) was used to stimulate prolactin release in 40 patients with IBS and in 40 healthy controls. In study 1, 10 IBS patients and 10 controls underwent pretreatment with pindolol (5HT1a antagonist) or placebo followed by buspirone. In study 2, 30 patients with IBS and 30 healthy controls had prolactin release stimulated by buspirone. Maternally separated and nonseparated rats were also treated with buspirone and prolactin monitored. Serotonin metabolites were measured together with the expression of the 5HT1a and serotonin transporter (SERT) gene. Pindolol produced a dose-dependent decrease in the buspirone prolactin response. Patients with IBS and maternally separated rats showed an exaggerated release of prolactin in response to buspirone. In the animal model, an increased turnover of 5HT was found in the brainstem together with a trend toward increased activity of the SERT gene. In conclusion altered central serotonin responses are found in both IBS and in an animal model.

Feeding and colonic distension provoke altered autonomic responses in irritable bowel syndrome

Objective. Alterations in autonomic balance, detectable by heart rate variability (HRV) analysis, have been shown to occur after a meal in patients with irritable bowel syndrome (IBS). There are few data on changes in sympathovagal responses in IBS to other forms of enteric stimulation such as colonic distension. The aim of this study was to determine the effects of colonic balloon distension on HRV in the fasting and the postprandial state in healthy subjects and in IBS patients. Material and methods. Eight IBS patients and 8 age- and gender-matched healthy subjects underwent unsedated descending colonic distension before and after a 1000 kcal liquid meal. Low- (LF) and high-frequency (HF) HRV band values obtained from 2-min ECG segments recorded before and during distension were compared between groups, and between fasting and postprandial states. A visual analogue scale was used to determine sensation during colonic distension. Results. HF values decreased significantly with feeding in IBS patients (p=0.01), but not in healthy subjects. The low-to-high frequency (LF/HF) ratio was significantly higher postprandially in IBS patients (p=0.02) and, additionally, was decreased (p<0.01) with colonic distension in the fed state, independently of colonic sensitivity or distending volume. Moreover, changes in the LF/HF ratio with distension in the fed versus the fasting state were negatively correlated in IBS patients but positively correlated in healthy subjects (both p<0.05). Conclusions. IBS patients demonstrated altered autonomic responses to feeding and colonic distension. Further studies should determine whether these alterations could explain the postprandial exacerbation of symptoms in IBS.

Defining the predictors of the placebo response in irritable bowel syndrome

We sought to determine the components of irritable bowel syndrome (IBS) clinical trials that correlate with higher levels of placebo response. We performed a systematic review of placebo-controlled trials in patients with IBS to assess which variables correlate with a higher placebo response. Placebo responses for global symptom improvement and for decreased abdominal pain were assessed. Univariate and multiple linear regression analyses were conducted. Higher rates of global improvement correlated with frequency of administration of study intervention ( r = .31, P = .03), duration of the study ( r = .28, P = .04), and overall treatment effect of the active agent being studied ( r = .33, P = .02). Higher rates of decreased abdominal pain correlated with the frequency of intervention ( r = .39, P = .02) and overall treatment effect ( r = .40, P = .01), whereas lower placebo response rates correlated with year of the study ( r = -.36, P = .03), median age ( r = -.38, P = .04), and duration of study run-in period ( r = -.33, P = .04). On multivariate analysis, global improvement in the placebo group was associated significantly with intervention frequency ( P = .0079), overall treatment response ( P = .0031), and parallel study design ( P = .0044). Decreased abdominal pain was associated significantly with frequency of intervention ( P = .0061) and overall treatment response ( P = .0128). In IBS studies, higher placebo response rates correlated with frequency of the intervention and with overall treatment effect of the active agent being studied. In designing IBS trials, it may be possible to minimize placebo response by less frequent dosing. In treating patients with IBS, it may be possible to harness the placebo response and maximize therapeutic response rates by more frequent dosing.

Visceral sensitivity and postprandial gastrocolonic response in irritable bowel syndrome (IBS)

Visceral sensitivity and postprandial gastrocolonic response in irritable bowel syndrome (IBS)