Introduction

Patients with irritable bowel syndrome (IBS) frequently seek dietary advice. However, few evidence-based options exist. Societal guidelines recommend traditional dietary advice (TDA) as first-line therapy, with the cumbersome and resource-intensive low FODMAP diet reserved as second-line therapy.
Recent pilot data suggests that the Mediterranean diet (MD), renowned for its general health benefits, improves the symptoms of IBS. Whether it can be considered another first-line dietary option is not known.

Aims & Methods

This randomized non-inferiority clinical trial assigned 139 individuals with IBS, from across the United Kingdom, to follow the MD (n=68) or TDA (n=71) for six weeks. The primary endpoint was the proportion of participants achieving clinical response, defined as a ≥50-point reduction in the IBS Symptom Severity Scale (IBS-SSS). Secondary outcomes included changes in IBS-SSS, psychological health, somatic symptom reporting, quality of life, diet satisfaction, and the Mediterranean Diet Adherence Screener (MEDAS).

Results

Baseline characteristics (mean age 40.4 [range 19-65] years, 80% female) and IBS-SSS (mean 309, SD 90) were similar between groups. On modified intention-to-treat analysis, the primary endpoint was met by 62% (95% CI 50%-73%) taking a MD versus 42% (95% CI 31%-55%) taking TDA. The difference in clinical response between the groups was in favor of the MD (20%, 95% CI 4%-36%), demonstrating it to be non-inferior based on the a priori defined requirement for the CI to exclude -5%. Rather, the MD was superior to TDA (odds ratio 2.3 [95% CI: 1.16-4.64], p = 0.017). There was a greater reduction in the mean IBS-SSS following a MD than TDA (-101.2 vs. -64.5, ∆-36.7 [95% C.I. -70.5 to -2.8], p=0.034). No significant differences were observed between the groups with regards to changes in mood, somatic symptoms, quality of life or diet satisfaction. The MEDAS significantly increased following a MD compared with TDA (p< 0.001).

Conclusion

The MD is non-inferior (rather, it demonstrated superiority) to TDA in managing the symptoms of IBS, and can be considered as another first-line dietary option.
Clinical trials registration: NCT05985018

Disclosure

Nil

Introduction

The low-FODMAP diet (LFD) is the most well-documented diet intervention for significantly improving irritable bowel syndrome (IBS) symptoms. The Mediterranean diet (MED), with plant-based foods, olive oil, fruits, herbs, wine, and lean proteins, has antioxidant properties that might ameliorate the low-grade inflammation characterizing the syndrome. The efficacy of the two diets combined in IBS is unknown.

Aims & Methods

Our primary aim was to examine the efficacy of combining LFD with MED diet components (MED-LFD) compared to the nutritional recommendations of the British National Institute for Health and Care Excellence (NICE) for managing non-constipation IBS.
Single-center, randomized, parallel groups design, single-masked, controlled study with six months of follow-up. We enrolled patients fulfilling Rome IV criteria with Bristol Stool Form Scale 3-7, IBS-SSS > 175, normal TSH, negative tTg-IgA/IgG, without either chronic systemic disorder or probiotic and/or antibiotic administration within a month before enrolment. Patients were randomized to either MED-LFD that included swapping high FODMAP for low FODMAP alternatives (1st phase), gradual introduction of foods rich in FODMAPs to test tolerance (2nd phase), and individualized diet based on personal tolerance (3rd phase) or a diet according to their energy needs adjusted to NICE recommendation for IBS. Patients were evaluated at baseline and follow-ups (1stFU: 4 weeks after initiation of intervention for NICE and at the end of phase 2 for MED-LFD, 2ndFU: at six 6 months) with: IBS-SSS (intervention responder: drop of >50 points), IBS-QOL, SF-12, modified for lower GI symptoms burden GSRS, and HADS.

Results

From July 2019 to April 2023, 108 patients (77.8% females, 40±11 yrs) were randomized (1:1) to MED-LFD or NICE diet groups. 92 (85.2%) patients completed the study. Primary endpoints: 1. Responders' rate was significantly higher in the MED-LFD group in the ITT and PP analysis at the 1st (81.5% vs. 57.4%, p=0.007 and 84.6% vs. 60.8%, p=0.007) and 2nd (68.5% vs. 40.7%, p=0.004 and 80.4% vs. 51.2%, p=0.004) FUs, respectively. 2. At both FUs, the MED-LFD group showed significantly greater improvement in symptom severity (IBS-SSS: 159±80 vs. 253±94 and 168±117 vs. 245±98). For all secondary endpoints (Table 1), patients in the MED-LFD group showed significantly higher improvement than the NICE group at each FU. Adherence rate was significantly higher in the MED-LFD group at both FUs (75% vs. 41% and 45% vs. 7%). No patient discontinued the intervention due to an adverse event. Eighteen (10 and eight in the MED-LFD and NICE groups, respectively) patients reported the use of rescue medication 26 times (12 and 14 in MED-LFD and NICE groups, respectively) during the intervention, including paracetamol (n=10), loperamide (n=14) and a combination of the two medications in two cases.

Table 1. Secondary endpoints: * denotes significant difference over baseline score at the different time points; $ denotes significant difference over comparator score at the FU.

Conclusion

Low-FODMAP diet combined with Mediterranean diet components is superior to the NICE nutritional recommendations for amelioration of IBS symptoms and improvement of quality of life of non-constipated IBS patients. The results are sustainable for six months

References

ClinicalTrials.gov identifier: NCT03997708

Introduction

Irritable bowel syndrome (IBS) is defined as a disorders of gut–brain interaction, which shows a high comorbidity tendency with anxiety and depression. Berberine has been suggested in previous studies to alleviate IBS-like symptoms, however, there is currently a lack of research investigating the clinical efficacy of berberine, its modulation of gut microbiota, and its influence on brain functional regulation in IBS patients with comorbid anxiety and depression.

Aims & Methods

We conducted a double-blind, randomized, placebo-controlled clinical trial to evaluate the therapeutic efficacy of berberine on clinical symptoms in patients with IBS comorbid depression and (or) anxiety. Eligible participants with IBS based on Rome IV criteria and comorbid anxiety/depression based on HAMA/HAMD criteria were recruited. Participants were randomly assigned to receive berberine (300mg tid) or placebo for 8 weeks. Follow-up assessments occurred at 4 and 8 weeks. We collected stool samples from patients and performed resting-state functional magnetic resonance imaging (rs-fMRI) for patients and healthy controls (HCs) recruited at the same period at baseline and after 8 weeks of treatment. Fractional amplitude of low-frequency fluctuations (fALFF) was used to assess brain activation.

Results

78 patients (40 berberine, 38 placebo) showed no significant baseline differences. Berberine had higher drug response rates at 4 weeks (61.86% vs. 32.26%, p=0.027) and 8 weeks (73.53% vs. 32.26%, p=0.003). Berberine also had higher drug efficacy rates for anxiety at 8 weeks (79.4% vs. 29.0%, p<0.001). Adverse reactions (constipation, nausea) were higher with berberine (35.00% vs. 13.16%, p=0.025) but not severe. Metagenomic sequencing revealed that, berberine decreased pathogenic bacteria (Eubacterium, Faecalibacterium, Collinsella, Streptococcus, Lachnospira) and increased beneficial bacteria (Bacteroides uniformis etc.). Correlations indicated associations between Streptococcus, Eubacterium and diarrhea and abdominal pain. Berberine suppressed flagella assembly and bacterial chemotaxis, accordingly reduced invasiveness by decreasing the abundance of Eubacterium and Streptococcus, and improved gastrointestinal symptoms. Also berberine may reduce the function of pyrimidine metabolism, one-carbon pool folate, and glycerophospholipid metabolism by suppressing the abundance of Collinsella, Faecalibacterium and enriching Bacteroides uniformis. Patients exhibited decreased activity in several brain regions compared to HC, while increasing activity in brain regions (cingulate gyrus, supplementary motor area, superior frontal gyrus, etc.) after berberine intake was shown. Placebo group showed limited activity increase. Activity in different brain regions negatively correlated with abdominal pain, anxiety scores.

Conclusion

Berberine significantly improves gastrointestinal symptoms and psychometric scale score in IBS patients comorbid depression and (or) anxiety. Berberine reduces the abundance of pathogenetic bacteria, suppresses bacterial chemotaxis, flagella assembly and accordingly decreases bacteria invasiveness, which correlate with symptom improvement. Berberine may affect metabolic pathways linked to anxiety and depression improvement. Following berberine intervention, the activity in these hypoactive brain regions significantly recovers. Moreover, berberine enhances the activity in brain regions related to the functionality of the whole-body action-cognition network and control network, which may serve as important neurobiological foundations for berberine's treatment of the gut-brain comorbidity.

Disclosure

There are no financial conflicts of interest to disclose

Introduction

Irritable bowel syndrome (IBS), which affects between 5 and 10% of the population according to the Rome III or IV diagnostic criteria, manifests as chronic abdominal pain associated with altered bowel transit. Moderate or severe IBS significantly impair the quality of life of patients, who are often dissatisfied with conventional treatments. In search of more effective solutions, many are turning to complementary and alternative approaches, such as hypnotherapy, whose effectiveness is well-established. Among these approaches, osteopathy, adopted by nearly 40% of patients in France, attracts growing interest. Single-centre studies with small sample sizes (30 to 40 patients) have reported promising but miscellaneous results, suggesting an improvement in symptoms and an effect on rectal sensitivity (1), or a transient effect on the severity of IBS (2).

Aims & Methods

Our study aims to evaluate the efficacy of visceral osteopathy on the severity of IBS symptoms in a French multicentre study. The trial, conducted as part of the 2015 National Hospital Clinical Research Program (PHRCN-PHRC-15-294), included adult patients suffering from IBS according to Rome III criteria and with moderate or severe IBS (IBS-SSS of 175 to 500 points at baseline). Patients were randomised into two groups: one with visceral osteopathy (three sessions performed over one month, two weeks apart) and one with placebo manipulation performed by the same osteopaths. Clinical characteristics (age, gender, BMI, IBS subtype according to bowel movements), anxiety (Spielberger State-Trait Anxiety Inventory, STAI-1 and STAI-2) and depression (Beck Depression Inventory or BDI II) levels, quality of life (IBS-QOL, ranging from 0 to 100, with 100 corresponding to the best quality of life), and IBS severity (IBS-SSS) were recorded. The primary objective of the study was the improvement in the IBS-SSS severity score at 2 months (1 month after the end of osteopathy). The effects on anxiety and depression levels as well as on quality of life were secondary objectives. The number of subjects to be included was calculated at 210 patients.

Results

Six centres included a total of 156 patients* (78 per group): mean age of 46 (± 15) years, 73% of women, 60% with IBS-C, 17% with IBS-D, 15% with IBS-M, and 8% with IBS-U. The mean IBS-SSS severity score was 336 (± 66) points (27.1% moderate severity and 72.9% severe with IBS-SSS > 300), with no difference between the two groups. Before inclusion, 61% of patients felt that osteopathy would be effective for their condition. At 2 months, the absolute decrease in the severity score (primary endpoint) was similar in both groups (52.4 ± 97.6 vs. 48.6 ± 98.9 points, p-value = 0.975), suggesting a placebo effect, as were the state-trait anxiety levels and quality of life (secondary endpoints).
* The monitoring committee terminated the study after a futility analysis on the first 156 patients because the study message could not be changed by including additional patients out of a planned total of 210.

Conclusion

In this first randomised multicentre study, visceral osteopathy was no more effective than a placebo manipulation in improving the severity of IBS, psychological comorbidities, or quality of life.

References

(1) Attali et al. Treatment of refractory irritable bowel syndrome with visceral osteopathy: Short-term and long-term results of a randomized trial. Journal of Digestive Diseases 2013; 14; 654–661. doi: 10.1111/1751-2980.12098
(2) Florance et al. Osteopathy improves the severity of irritable bowel syndrome: a pilot randomized sham-controlled study. European Journal of Gastroenterology & Hepatology 2012 ; 24 (8) : p 944-949. DOI: 10.1097/MEG.0b013e3283543eb7

Disclosure

Nothing to disclose