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

Introduction

Helicobacter pylori infection affects approximately half of the global population and may lead to sever complications, including gastric cancer. Current antibiotic-based therapies face the challenge of rising resistance rates. Therefore, there is urgent medical need for an effective vaccine. Despite extensive research efforts, no H. pylori vaccine has yet made it to clinical application. Aim of our study is the development of a novel multi-epitope-based H. pylori vaccine

Aims & Methods

Sixteen selected B- and T-cell epitopes from six key virulence factors were fused to create the Multi-Epitope-Unit (MEU) antigen. Two vaccine formulations were evaluated: MEU combined with flagellin as adjuvant, and MEU incorporated into the Modified Vaccinia virus Ankara (MVA) genome for enhanced antigen delivery. The efficacy was assessed in murine models using H. pylori SS1 infection, with evaluation in both prophylactic and therapeutic settings. To explore the possible clinical relevance, crude antigens from 48 human clinical isolates of H. pylori obtained from international healthcare centers were tested for binding capacity with anti-MEU antibodies generated from immunized mice.

Results

Both vaccine formulations elicited robust MEU-specific antibody and CD4+ T-cell responses. The vaccines generated a balanced Th1/Th2 immune response profile and significantly elevated CD4+NKT-like cell levels. Complete bacterial clearance was achieved with protein-based vaccination followed by MVA boost or two doses of MVA vaccine in both prevention and treatment models. Binding assays revealed that anti-MEU antibodies demonstrated positive binding capacity to crude antigens from all 48 tested human clinical isolates (100% reactivity), confirming broad-spectrum recognition across diverse H. pylori strains from different geographical origins.

Conclusion

This study represents groundbreaking research, presenting a novel promising H. pylori vaccine candidate. The comprehensive testing against 48 human clinical isolates from international healthcare units provides unprecedented evidence of functional immune responses. Our data demonstrate 100% binding reactivity of anti-MEU antibodies to crude antigens from ALL tested clinical isolates, representing diverse geographical origins and strain variations. This finding demonstrates for the first time that a H. pylori vaccine can generate immune responses effective against a vast spectrum of human pathogenic strains, which has eluded all previous vaccine approach failures and poses high expectation for a successful clinical application. Our multi-epitope vaccine represents a novel H. pylori vaccine development, being the first to demonstrate both complete bacterial clearance in preclinical models as well as a broad-spectrum reactivity against human clinical isolates. These results provide strong scientific rationale for advancing to toxicology studies and clinical evaluation, offering the first genuine hope for both prevention and treatment of H. pylori infections in human populations worldwide.

Disclosure

BK, HM and VW are employed by Iguana Biotechnology. The remaining authors declare no conflicts of interest.