Randomised clinical trial: individual versus group hypnotherapy for irritable bowel syndrome.

BACKGROUND: Gut-directed hypnotherapy improves symptoms for patients with irritable bowel syndrome (IBS). Group hypnotherapy, as well as hypnotherapy administered by nurses, can increase treatment availability, but there are few comparisons between individual and group-based hypnotherapy. AIM: We aimed to evaluate and compare the effectiveness of nurse-administered hypnotherapy for IBS delivered individually or in groups. METHODS: IBS patients were randomised to individual or group hypnotherapy (8 sessions, 12 weeks). The primary endpoint was changes in severity of IBS symptoms. A responder was defined as reduction of IBS severity scoring system (IBS-SSS) ≥50 points at the end of treatment compared to baseline. The effects on extracolonic and psychological symptoms, and quality of life were also assessed. Symptoms were also followed up 6 months after treatment start. RESULTS: A total of 119 patients were randomised (61 individual, 58 group hypnotherapy). Patients reported improvements in IBS symptoms (IBS-SSS) (individual: 332 (273-401) (median, IQR), versus 216 (140-308), (p < 0.0001), group: 315 (239-382), versus 217 (149-314), (p < 0.0001)), with no differences between the groups (p = 0.16). Extracolonic symptoms, psychological symptoms and quality of life also improved, without clear differences between the groups. Sixty-nine percent of the individual hypnotherapy patients were responders after treatment versus 57% of the group hypnotherapy patients (p = 0.25). Symptom improvements were also seen at follow-up. CONCLUSIONS: Nurse-administered gut-directed hypnotherapy, delivered individually or in groups, relieves IBS symptoms, improves psychological symptoms and quality of life. Group hypnotherapy can be an efficacious alternative, enabling more patients to benefit from the treatment (ClinicalTrials.gov ID no of study: NCT03432078).

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.

The Effects of Human Milk Oligosaccharides on Gut Microbiota, Metabolite Profiles and Host Mucosal Response in Patients with Irritable Bowel Syndrome.

BACKGROUND: Human milk oligosaccharide supplementation safely modulates fecal bifidobacteria abundance and holds the potential to manage symptoms in irritable bowel syndrome (IBS). Here, we aimed to determine the role of a 4:1 mix of 2'-O-fucosyllactose and lacto-N-neotetraose (2'FL/LNnT) on the modulation of the gut microbiota composition and host mucosal response, as well as the link between the bifidobacteria abundance and metabolite modulation, in IBS patients. METHODS: Biological samples were collected from IBS patients (n = 58) at baseline and week 4 post-supplementation with placebo, 5 g or 10 g doses of 2'FL/LNnT. The gut microbiota composition, metabolite profiles and expression of genes related to host mucosal response were determined. RESULTS: Moderate changes in fecal, but not mucosal, microbial composition (ß-diversity) was observed during the intervention with higher dissimilarity observed within individuals receiving 10g 2'FL/LNnT compared to placebo. Both fecal and mucosal Bifidobacterium spp. increased after 2'FL/LNnT intake, with increased proportions of Bifidobacterium adolescentis and Bifidobacterium longum. Moreover, the intervention modulated the fecal and plasma metabolite profiles, but not the urine metabolite profile or the host mucosal response. Changes in the metabolite profiles were associated to changes in bifidobacteria abundance. CONCLUSION: Supplementation with 2'FL/LNnT modulated the gut microbiota, fecal and plasma metabolite profiles, but not the host mucosal response in IBS. Furthermore, the bifidogenic effect was associated with metabolite modulation. Overall, these findings support the assertion that 2'FL/LNnT supplementation modulate the intestinal microenvironment of patients with IBS, potentially related to health.

Human milk oligosaccharide supplementation in irritable bowel syndrome patients: A parallel, randomized, double-blind, placebo-controlled study.

OBJECTIVES: Human milk oligosaccharides safely and beneficially impact bifidobacteria abundance in healthy adults, while their effects in patients with irritable bowel syndrome (IBS) are unknown. Hence, we aimed to determine the dose of 4:1 mix of 2'-O-fucosyllactose and Lacto-N-neotetraose (2'FL/LNnT) that increases fecal bifidobacteria abundance without aggravating overall gastrointestinal symptoms in IBS patients in a randomized, double-blind, controlled study. Additionally, the impact of 2'FL/LNnT on the fecal bacterial profile was assessed. METHODS: Irritable bowel syndrome patients diagnosed according to the Rome IV criteria received placebo (glucose), or 5 g or 10 g 2'FL/LNnT for 4 weeks followed by a four-week follow-up period. Gastrointestinal Symptom Rating Scale-IBS was used to assess gastrointestinal symptom severity; fecal microbiota composition was evaluated by GA-map™ Dysbiosis Test. RESULTS: Of the included 60 patients, two (one placebo and one 10 g) discontinued prematurely. Fecal bifidobacteria abundance was increased at week 4, but not at week 8, in the 10 g group compared to the other groups. Severity of overall or individual gastrointestinal symptoms did not differ between the groups at week 4 or 8, and no symptom deterioration was seen in any of the groups. The 10 g dose influenced overall fecal microbiota composition, and responders-defined as bifidobacteria increase ≥50%-could be discriminated from non-responders based on fecal microbiota modulation. CONCLUSIONS: The 10 g dose of 2'FL/LNnT induced an increase in the beneficial Bifidobacterium spp. without aggravating gastrointestinal symptoms in patients with IBS. This approach may be worthwhile to modulate gut microbiota of IBS patients toward a healthier profile.

Randomized clinical trial: Effects of Aloe barbadensis Mill. extract on symptoms, fecal microbiota and fecal metabolite profiles in patients with irritable bowel syndrome.

BACKGROUND: Aloe barbadensis Mill. (Aloe) with potential prebiotic effects has been suggested to reduce symptoms in patients with irritable bowel syndrome (IBS). We therefore aimed to determine the effects of an Aloe extract on symptoms of IBS, and evaluate whether effects may be mediated by fecal microbiota and metabolites in a randomized, double-blind, controlled trial. METHODS: Patient with IBS diagnosed according to the ROME III criteria (all subtypes), received Aloe or control treatment (inulin) for 4 weeks. IBS Symptom Severity Score (IBS-SSS) was assessed, and fecal samples collected before and at end of treatment. Fecal microbiota composition and metabolomic profile were determined. KEY RESULTS: In total, 160 IBS patients completed the study. The overall severity of IBS symptoms was reduced in both Aloe and control treatment groups (P < .001, both groups, comparing baseline vs end of treatment), without difference between groups (P = .62). The frequency of responders (IBS-SSS reduction ≥ 50) did not differ between Aloe treatment (n = 33, 39%) and control (n = 34, 45%) (P = .49). However, fecal microbiota and metabolite profiles differed between Aloe, but not control treatment responders and non-responders both before and after treatment. CONCLUSION: In a mixed group of IBS patients, Aloe was not superior to control treatment, although it showed potential to reduce IBS symptom severity in subsets of IBS patients which could be predicted by fecal microbiota and metabolite profiles. ClinicalTrials.gov no: NCT01400048.

A Perspective on Brain-Gut Communication: The American Gastroenterology Association and American Psychosomatic Society Joint Symposium on Brain-Gut Interactions and the Intestinal Microenvironment.

BACKGROUND: Alterations in brain-gut communication and the intestinal microenvironment have been implicated in a variety of medical and neuropsychiatric diseases. Three central areas require basic and clinical research: (1) how the intestinal microenvironment interacts with the host immune system, central nervous system, and enteric nervous system; (2) the role of the intestinal microenvironment in the pathogenesis of medical and neuropsychiatric disease; and (3) the effects of diet, prebiotics, probiotics, and fecal microbiota transplantation on the intestinal microenvironment and the treatment of disease. METHODS: This review article is based on a symposium convened by the American Gastroenterology Association and the American Psychosomatic Society to foster interest in the role of the intestinal microenvironment in brain-gut communication and pathogenesis of neuropsychiatric and biopsychosocial disorders. The aims were to define the state of the art of the current scientific knowledge base and to identify guidelines and future directions for new research in this area. RESULTS: This review provides a characterization of the intestinal microbial composition and function. We also provide evidence for the interactions between the intestinal microbiome, the host, and the environment. The role of the intestinal microbiome in medical and neuropsychiatric diseases is reviewed as well as the treatment effects of manipulation of the intestinal microbiome. CONCLUSIONS: Based on this review, opportunities and challenges for conducting research in the field are described, leading to potential avenues for future research.

A Pilot Study of the Effect of Aloe barbadensis Mill. Extract (AVH200®) in Patients with Irritable Bowel Syndrome: a Randomized, Double-Blind, Placebo-Controlled Study.

BACKGROUND AND AIMS: Few effective treatment options exist for patients with irritable bowel syndrome (IBS), and many patients state the use of aloe vera products reduce their symptoms. The aim of this pilot study was to investigate the effect of Aloe barbadensis Mill. Extract (AVH200®) in adult patients with IBS in a randomized, double-blind, placebo controlled study. METHODS: Sixty-eight adult patients diagnosed with IBS according to the Rome III criteria were randomized to receive AVH200® or matching placebo for four weeks. Symptom questionnaires were completed on a weekly basis and the patients were asked if they had had adequate relief of their gastrointestinal symptoms. RESULTS: A tendency towards a higher proportion of responders in the aloe vera group (55%) vs. placebo (31%), (p=0.09) was observed, and the proportion of subjects who reported adequate relief at least 50% of the weeks during the treatment period tended to be larger in the aloe vera vs. placebo group (33% vs. 14%; p=0.12). The overall severity of the gastrointestinal symptoms was reduced in the aloe vera group (314+/-83 vs. 257+/-107; p=0.003) but not the placebo group (276+/-88 vs. 253+/-100; NS), without difference between the groups (p=0.10). AVH200® was well tolerated and no serious adverse events were observed. CONCLUSION: Even though the primary endpoint was not met, AVH200® seems to be a promising treatment option for patients with IBS owing to the positive results seen within the secondary endpoints. This study may have been underpowered to detect a clinically meaningful difference between the treatment groups, and therefore larger randomized, controlled studies are required to confirm these results and to elucidate potential mechanisms explaining its effect.

Nurse-Administered, Gut-Directed Hypnotherapy in IBS: Efficacy and Factors Predicting a Positive Response.

Hypnotherapy is an effective treatment in irritable bowel syndrome (IBS). It is often delivered by a psychotherapist and is costly and time consuming. Nurse-administered hypnotherapy could increase availability and reduce costs. In this study the authors evaluate the effectiveness of nurse-administered, gut-directed hypnotherapy and identify factors predicting treatment outcome. Eighty-five patients were included in the study. Participants received hypnotherapy by a nurse once/week for 12 weeks. Patients reported marked improvement in gastrointestinal (GI) and extra-colonic symptoms after treatment, as well as a reduction in GI-specific anxiety, general anxiety, and depression. Fifty-eight percent were responders after the 12 weeks treatment period, and of these 82% had a favorable clinical response already at week 6. Women were more likely than men to respond favorably to the treatment. Nurse-administered hypnotherapy is an effective treatment for IBS. Being female and reporting a favorable response to treatment by week 6 predicted a positive treatment response at the end of the 12 weeks treatment period.

Effects on gastrointestinal transit and antroduodenojejunal manometry after gut-directed hypnotherapy in irritable bowel syndrome (IBS).

BACKGROUND: Gut-directed hypnotherapy is an effective treatment in irritable bowel syndrome (IBS) but little is known about the mechanisms of action. In this study we aimed to investigate the effects on gastrointestinal motility when treating IBS with gut-directed hypnotherapy. METHODS: We randomized 90 patients with IBS, refractory to standard management to receive gut-directed hypnotherapy 1 h/week for 12 weeks or supportive treatment for the same time period. Eighty-one subjects (40 hypnotherapy, 41 controls) could be evaluated by one or more of the following investigations, both before and after the intervention: gastric emptying time, small bowel transit time, colonic transit time, and antroduodenojejunal manometry. RESULTS: No significant differences in gastric emptying time, small bowel transit time, or colonic transit time was found when comparing the baseline and post-intervention measurements in the hypnotherapy group or in the control group. The same was true concerning the results of the antroduodenojejunal manometry. However, there was a numerical trend toward a higher number of migrating motor complexes at manometry and an accelerated gastric emptying time after hypnotherapy that did not reach statistical significance. CONCLUSIONS: In this study, we were not able to find evidence for long-standing effects on gastrointestinal motility as a mediator of the effects on IBS when treating the condition with gut-directed hypnotherapy. Further research to understand the mechanism of action is needed.

Meditation over medication for irritable bowel syndrome? On exercise and alternative treatments for irritable bowel syndrome.

Complimentary alternative treatment regimens are widely used in irritable bowel syndrome (IBS), but the evidence supporting their use varies. For psychological treatment options, such as cognitive behavioral therapy, mindfulness, gut-directed hypnotherapy, and psychodynamic therapy, the evidence supporting their use in IBS patients is strong, but the availability limits their use in clinical practice. Dietary interventions are commonly included in the management of IBS patients, but these are primarily based on studies assessing physiological function in relation to dietary components, and to a lesser degree upon research examining the role of dietary components in the therapeutic management of IBS. Several probiotic products improve a range of symptoms in IBS patients. Physical activity is of benefit for health in general and recent data implicates its usefulness also for IBS patients. Acupuncture does not seem to have an effect beyond placebo in IBS. A beneficial effect of some herbal treatments has been reported.

Long-term effects of hypnotherapy in patients with refractory irritable bowel syndrome.

OBJECTIVE: Gut-directed hypnotherapy is considered to be an effective treatment in irritable bowel syndrome (IBS) but few studies report the long-term effects. This retrospective study aims to evaluate the long-term perceived efficacy of gut-directed hypnotherapy given outside highly specialized hypnotherapy centers. METHODS: 208 patients, who all had received gut-directed hypnotherapy, were retrospectively evaluated. The Subjective Assessment Questionnaire (SAQ) was used to measure changes in IBS symptoms, and patients were classified as responders and non-responders. Patients were also asked to report changes in health-care seeking, use of drugs for IBS symptoms, use of alternative non-pharmacological treatments, and if they still actively used hypnotherapy. RESULTS: Immediately after hypnotherapy, 103 of 208 patients (49%) were responders and 75 of these (73%) had improved further at the follow-up 2-7 years after hypnotherapy (mean 4 years). A majority of the responders still used hypnotherapy on a regular basis at follow-up (73%), and the responders reported a greater reduction in health-care seeking than non-responders. A total of 87% of all patients reported that they considered gut-directed hypnotherapy to be worthwhile, and this differed between responders and non-responders (100% vs. 74%; p < 0.0001). CONCLUSION: This long-term follow-up study indicates that gut-directed hypnotherapy in refractory IBS is an effective treatment option with long-lasting effects, also when given outside highly specialized hypnotherapy centers. Apart from the clinical benefits, the reduction in health-care utilization has the potential to reduce the health-care costs.

Effects of gut-directed hypnotherapy on IBS in different clinical settings-results from two randomized, controlled trials.

OBJECTIVES: Gut-directed hypnotherapy has been found to be effective in irritable bowel syndrome (IBS). However, randomized, controlled studies are rare and few have been performed outside highly specialized research centers. The objective of this study was to study the effect of gut-directed hypnotherapy in IBS in different clinical settings outside the traditional research units. METHODS: The study population included IBS patients refractory to standard management. In study 1, patients were randomized to receive gut-directed hypnotherapy (12 sessions, 1 h/week) in psychology private practices or supportive therapy, whereas patients were randomized to receive gut-directed hypnotherapy in a small county hospital or to serve as waiting list controls in study 2. Gastrointestinal symptom severity and quality of life were evaluated at baseline, at 3 months follow-up and after 1 year. RESULTS: We randomized 138 IBS patients refractory to standard management, 90 in study 1 and 48 in study 2. In both the studies, IBS-related symptoms were improved at 3 months in the gut-directed hypnotherapy groups (P<0.05), but not in the control groups (ns). In study 1, a significantly greater improvement of IBS-related symptom severity could be detected in the gut-directed hypnotherapy group than in the control group (P<0.05), and a trend in the same direction was seen in study 2 (P=0.17). The results seen at 3 months were sustained up to 1 year. CONCLUSIONS: Gut-directed hypnotherapy is an effective treatment alternative for patients with refractory IBS, but the effectiveness is lower when the therapy is given outside the highly specialized research centers.

A slow caloric satiety drinking test in patients with temporary and permanent gastric electrical stimulation.

OBJECTIVES: Improvement of gastric accommodation has been proposed as a potential explanation for the positive effect of gastric electrical stimulation (GES) on nausea/vomiting. A drinking test has been suggested as a noninvasive measure of gastric accommodation capacity. METHODS: Eight patients with therapy refractory nausea and vomiting and nonapproved diagnosis for GES (chronic intestinal pseudo-obstruction (CIP, n=1), functional dyspepsia (FD, n=3), postsurgical gastroparesis (PSGP, n=4) underwent temporary percutaneous GES for 10-14 days, randomized to stimulation ON or OFF, respectively. 19 patients [CIP (n=1), diabetic gastroparesis (n=5), FD (n=5), idiopathic gastroparesis (n=4), PSGP (n=4)] received permanent GES (Enterra, Medtronic) (follow-up at baseline, 6 and 12 months). At the end of each stimulation period a slow caloric satiety drinking test was performed (Nutridrink 1.5 kcal/ml, 15 ml/min). RESULTS: Healthy volunteers had higher drinking capacity compared to patients at baseline (1630 + or - 496 kcal vs. 887 + or - 412; P<0.001) and less composite symptom score (128 + or - 51 vs. 235 + or - 83; P<0.001). With temporary percutaneous GES, there was no significant change in drinking capacity during stimulation ON versus OFF (746 + or - 383 vs. 734 + or - 427 kcal) and symptom severity at the drinking test was unchanged. For patients having permanent GES there was no significant difference at 6 months (876 + or - 277 kcal) versus baseline, and no difference between symptomatic responders and nonresponders in change in drinking capacity (P=0.7). CONCLUSION: GES had no effect on proximal gastric function as evaluated by the slow caloric satiety drinking test. This seems to be the case for patients with approved as well as nonapproved indications for GES, and irrespective of the symptomatic response.

Hypnosis for irritable bowel syndrome: the quest for the mechanism of action.

Irritable bowel syndrome (IBS) is a very common condition in the Western part of the world, and it accounts for a large proportion of the workload of a gastroenterologist. Unfortunately, the pathogenesis and pathophysiology of the syndrome are incompletely understood, and the treatment options are limited. However, hypnotherapy is one treatment option that has proven to be very useful in IBS. The mechanisms of action explaining why hypnosis is effective for IBS are not altogether known, but recent studies have shed some light on this issue. These studies, and what can be learned from them about how hypnosis impacts IBS, are reviewed in this article. Hypnosis may affect IBS partly through changes in colorectal sensitivity and improvement in psychological factors. The effects on GI motility and the autonomic nervous system are less clear and need further evaluation.

Treatment with hypnotherapy reduces the sensory and motor component of the gastrocolonic response in irritable bowel syndrome.

OBJECTIVE: Postprandial symptoms in irritable bowel syndrome are common and relate to an exaggerated motor and sensory component of the gastrocolonic response. We investigated whether this response can be affected by hypnotherapy. METHODS: We included 28 patients with irritable bowel syndrome refractory to other treatments. They were randomized to receive gut-directed hypnotherapy 1 hour per week for 12 weeks (N = 14) or were provided with supportive therapy (control group; N = 14). Before randomization and after 3 months, all patients underwent a colonic distension trial before and after a 1-hour duodenal lipid infusion. Colonic sensory thresholds and tonic and phasic motor activity were assessed. RESULTS: Before randomization, reduced thresholds after vs. before lipid infusion were seen in both groups for all studied sensations. At 3 months, the colonic sensitivity before duodenal lipids did not differ between groups. Controls reduced their thresholds after duodenal lipids for gas (22 +/- 1.7 mm Hg vs. 16 +/- 1.6 mm Hg, p <.01), discomfort (29 +/- 2.9 mm Hg vs. 22 +/- 2.6 mm Hg, p <.01), and pain (33 +/- 2.7 mm Hg vs. 26 +/- 3.3 mm Hg, p <.01), whereas the hypnotherapy group reduced their thresholds after lipids only for pain (35 +/- 4.0 mm Hg vs. 29 +/- 4.7 mm Hg, p <.01). The colonic balloon volumes and tone response at randomization were similar in both groups. At 3 months, baseline balloon volumes were lower in the hypnotherapy group than in controls (83 +/- 14 ml vs. 141 +/- 15 ml, p <.01). In the control group, reduced balloon volumes during lipid infusion were seen (141 +/- 15 ml vs. 111 +/- 19 ml, p <.05), but not after hypnotherapy (83 +/- 14 ml vs. 80 +/- 16 ml, p >.20). CONCLUSION: Hypnotherapy reduces the sensory and motor component of the gastrocolonic response in patients with irritable bowel syndrome. These effects may be involved in the clinical efficacy of hypnotherapy in IBS.