A53 SACCHAROMYCES BOULARDII CNCM I-745 IMPROVES ANXIETY-LIKE BEHAVIOR AND RESCUES DYSMOTILITY IN A HUMANIZED MOUSE MODEL OF IRRITABLE BOWEL SYNDROME WITH CO-MORBID ANXIETY

Abstract

Background

Irritable bowel syndrome (IBS) is one of the most common conditions seen by gastroenterologists for which there is no effective cure. The pathophysiology of IBS is multifactorial and poorly understood, but the condition is characterized by chronic abdominal pain accompanied by altered bowel habits in the absence of an underlying structural abnormality. IBS is frequently associated with psychiatric co-morbidities such as anxiety and depression and has been considered a disorder of gut-brain communication. We previously developed a humanized mouse model of IBS with co-morbid anxiety (IBS+A) by colonizing germ-free mice with fecal microbiota of IBS+A patients.

Aims

To test the therapeutic potential of the probiotic yeast Saccharomyces boulardii CNCM I-745 (S. bou) in preventing the transfer of the IBS+A phenotype and investigated underlying mechanisms.

Methods

Germ-free Swiss-Webster mice were colonized with fecal microbiota from an IBS+A patient or from a healthy subject (controls) and after three weeks they were gavaged daily for two weeks with 3g/kg/day of the probiotic S. bou (Biocodex–France) or water. Behavior, intestinal motility and permeability were assessed at sacrifice. Potential mechanisms were assessed by microbiota 16S rRNA gene sequencing, gene expression by Nanostring Counter Gene Expression and indole quantification by absorption using Kovak’s reagent.

Results

IBS+A colonized mice developed 25% faster gastrointestinal transit (P<0.05) and had a 3-fold longer latency time in the step-down test (P<0.001), indicative of anxiety-like behaviour compared with controls. S. bou normalized gastrointestinal transit (P<0.05) and shortened by 50% the step-down latency (P<0.01), compared to water-treated mice. Microbiota of IBS+A colonized mice had higher abundance of Unc. Erysipelotrichaceae and Unc. Coriobacteriaceae, and lower abundance of Oscillospira, Weissela, and Fructubacillus. S. bou treatment prevented these changes and the microbiota was similar to controls. Predicted function analysis in S. bou treated mice suggested higher number of genes implicated in indole biosynthesis (P<0.05) and S. bou increased indole levels by 20% in vitro. Finally, Trpv1, a gene implicated in visceral hypersensitivity and anxiety, was increased by 2-fold in IBS+A colonized mice compared with controls (P<0.001), and this was reverted by 20% (P<0.05) by S. bou treatment.

Conclusions

Our data indicate that Saccharomyces boulardii CNCM I-745 supplementation improves the intestinal and behavioral phonotype that is induced by IBS+A microbiota in mice. Putative mechanisms include regulation of indole production by bacteria and regulation of host Trpv1 gene expression. The results prompt investigation of S. bou in IBS patients with co-morbid anxiety.

Funding Agencies

Biocodex – Gentilly – France