Introduction

Irritable bowel syndrome (IBS) is one of the most common disorders of the gut–brain interaction, associated with intestinal microbiota composition, increased gut permeability and psychosocial disturbances^1,2. The pasteurized form of the next generation beneficial microbe, Akkermansia muciniphila, improves gut barrier function and reduces colonic hypersensitivity and anxiety-like behavior in preclinical setting, showing potential in modulation of the gut-brain-axis³.

Aims & Methods

This human study aimed at exploring the effects of pasteurized A. muciniphila on IBS symptoms and psychological function in subjects with moderate IBS.
In a 12-week, randomized, double-blind, placebo-controlled exploratory trial at a single center in Germany, 48 selected individuals diagnosed with IBS (Rome IV criteria), with moderate symptoms based on the IBS Severity Scoring System (IBS-SSS score ≥ 175), were randomized to pasteurized Akkermansia muciniphila at a daily dose of around 30 billion versus placebo in a 2:1 ratio. A main outcome, although not statistically powered, was mean change in IBS-SSS scores from baseline to 12-week endpoint (NCT05348642).

Results

The oral intake of pasteurized Akkermansia muciniphila was very well tolerated. Intent-to-treat analysis revealed clinically meaningful mean improvements from baseline to the 12-week endpoint in the main outcome measure (IBS-SSS) for both pasteurized A. muciniphila (-147.45, SD 94.08) and placebo (-122.25, SD 90.07). Although the pasteurized A. muciniphila group reported numerically higher improvement than the placebo group, the difference between the groups was not statistically significant. The IBS-SSS parameter had decreased already by 44% and 37% of the initial values in the verum and placebo arms respectively at the 2-week timepoint, reflecting a relatively quick effect. At the level of the psychological scores, the Hospital Anxiety and Depression Scores were in the normal range at baseline, improved with 10 and 5% in the verum group, and worsened by 11 and 35% in the placebo arm from the initial anxiety and depression parameters respectively.

Conclusion

Pasteurized Akkermansia muciniphila showed clinically meaningful but not statistically significant improvement over placebo in IBS symptoms in subjects with moderate IBS. The psychological scores improved mildly in the verum group while worsening in the placebo arm. These results support the potential of pasteurized Akkermansia muciniphila to modulate the gut–brain interaction in IBS subjects.

References

1 Barbara G, Grover M, Bercik P, Corsetti M, Ghoshal UC, Ohman L, Rajilić-Stojanović M. Rome foundation working team report on post-infection irritable bowel syndrome. Gastroenterology 2019;156:46–58,
2 Huang HL, Chen HT, Luo QL, Xu HM, He J, Li YQ, Zhou YL, Yao F, Nie YQ, Zhou YJ. Relief of irritable bowel syndrome by fecal microbiota transplantation is associated with changes in diversity and composition of the gut microbiota. J Dig Dis. 2019;20:401-408
3 Paper with the scientific data submitted to and currently in review by peer reviewed journal.

Disclosure

The trial is sponsored by The Akkermansia Company SA that is developing and commercializing pasteurized Akkermansia muciniphila.