Pasteurized akkermansia muciniphila improves irritable bowel syndrome-like symptoms and related behavioral disorders in mice

Gut Microbes. 2024 Jan-Dec;16(1):2298026. doi: 10.1080/19490976.2023.2298026. Epub 2024 Jan 3.

Abstract

Gut - brain communications disorders in irritable bowel syndrome (IBS) are associated with intestinal microbiota composition, increased gut permeability, and psychosocial disturbances. Symptoms of IBS are difficult to medicate, and hence much research is being made into alternative approaches. This study assesses the potential of a treatment with pasteurized Akkermansia muciniphila for alleviating IBS-like symptoms in two mouse models of IBS with different etiologies. Two clinically relevant animal models were used to mimic IBS-like symptoms in C57BL6/J mice: the neonatal maternal separation (NMS) paradigm and the Citrobacter rodentium infection model. In both models, gut permeability, colonic sensitivity, fecal microbiota composition and colonic IL-22 expression were evaluated. The cognitive performance and emotional state of the animals were also assessed by several tests in the C. rodentium infection model. The neuromodulation ability of pasteurized A. muciniphila was assessed on primary neuronal cells from mice dorsal root ganglia using a ratiometric calcium imaging approach. The administration of pasteurized A. muciniphila significantly reduced colonic hypersensitivity in both IBS mouse models, accompanied by a reinforcement of the intestinal barrier function. Beneficial effects of pasteurized A. muciniphila treatment have also been observed on anxiety-like behavior and memory defects in the C. rodentium infection model. Finally, a neuroinhibitory effect exerted by pasteurized A. muciniphila was observed on neuronal cells stimulated with two algogenic substances such as capsaicin and inflammatory soup. Our findings demonstrate novel anti-hyperalgesic and neuroinhibitory properties of pasteurized A. muciniphila, which therefore may have beneficial effects in relieving pain and anxiety in subjects with IBS.

Keywords: IBS; Pasteurized akkermansia muciniphila; anxiety-like disorders; colonic hypersensitivity; memory impairment; neuroinhibition.

MeSH terms

  • Animals
  • Gastrointestinal Microbiome*
  • Humans
  • Irritable Bowel Syndrome* / therapy
  • Maternal Deprivation
  • Mice
  • Verrucomicrobia / physiology

Supplementary concepts

  • Akkermansia muciniphila

Grants and funding

This work was supported by co-financing from The Akkermansia Company™ (Belgium) and supported by a research agreement from the Walloon Region (agreement 8206), the French Ministère de la Recherche et de la Technologie (NeuroDol laboratory [INSERM 1107]), the Region Auvergne-Rhône-Alpes and FEDER, No. Thématiques émergentes, Pack Ambition Recherche; the French Government IDEX-ISITE Initiative, No. 16-IDEX-0001-CAP 20-25, and the Clermont Auvergne Métropole, No “Recherche-Action” project. P.D.C. is research director for the FNRS and recipient of a Projet de Recherche PDR-convention: FNRS T.0030.21 and FRFS-WELBIO: WELBIO-CR-2022A-02, EOS: program no. 40007505.