IBS ANIMAL MODELS

In the same study, we observed in a model of rats having a visceral hypersensitivity induced by intrarectal instillation of high concentration of butyrate (mimicking the IBS visceral hypersensitivity without any sign of inflammation).

We also noted that the same probiotic reduces significantly the pain perception and is as efficient as the injection of morphine at the dosage of 0.1mg/kg. We demonstrated that the mechanism of action of this probiotic had impacted the expression of cannabinoid and opioid receptors.

Validated in vivo model

We commonly use a validated in vivo model to evaluate the effects of prebiotics, probiotics or other compounds in the intestinal well-being or in the visceral pain (induced by butyrate) mimicking the features of IBS that is the colorectal distension and not an invasive method. The colonic pain perception in rats can be assessed using a balloon inserted intra-rectally and inflated by a barostat system.

The tools associated to evaluate the properties of tested substances are:

- modification of the fecal flora by conventional bacteriologic methods.

- expression of the therapeutic target at the mRNA level (Real-Time PCR) and at the protein level (IHC, Western Blot).

IBD ANIMAL MODELS

As more and more sophisticated IBD models become available, we have to exploit the unique potential of each model to ask specific questions. Although no single animal model recapitulates all of the pathogenic and clinical features of human IBD, each animal model contributed to the improved understanding of the mechanisms underlying initiation and perpetuation of chronic intestinal inflammation.

Colitis induced by chemical agents:

-The model of colitis induced by TNBS

-The model of colitis induced by DSS (severe or chronic)

- The model of colitis induced by oxazolone

Genetically modified animal model:

IL10-/- mice, TLR deficient mice

Other models can be used:

The CD45RBHi transfer model

The model of ileitis induced by indomethacine

Which model to choose?

Based on our expertise, we are able to propose the most relevant animal model to evaluate the anti-inflammatory properties of the tested compounds among these different models.

Quantitative and qualitative tools will be used to evaluate the effect of the tested compounds at the clinical macroscopical, histological, mRNA and protein levels (for pro- and anti-inflammatory mediators, therapeutic targets).