Irritable bowel syndrome (IBS) is a functional disorder causing recurrent abdominal pain associated with changes in bowel habits. It is the most common disorder of gut-brain interaction diagnosed in gastroenterology and has a worldwide prevalence of 9.2% [1]. Its etiology involves complex interactions of factors such as altered immune and barrier functions of the mucosa, central nervous system dysregulation of gut signaling and microbial dysbiosis within the gut. Modulating the gut microbiota, as a means of alleviating symptoms may therefore be an attractive prevention and treatment option. Indeed probiotics, which are live microorganisms that, when administered in adequate amounts confer a health benefit on the host [2], were shown to be beneficial in terms of improvement of global IBS symptoms [3], however the effects are strain specific. In this context, we developed a methodology combining in vitro and in vivo tests to maximize the probability of identifying novel strains with probiotic effects in IBS. We screened a collection of 41 strains of lactic acid bacteria. Bacterial supernatants were analyzed for the production of short chain fatty acids (SCFAs) and aryl hydrocarbon receptor (AhR) agonists, using gas chromatography and HepG2 Lucia reporter cell line, respectively. The strains were also tested in vitro for cytokine production after co-incubation on TNF-α challenged HT-29 cells or non-stimulated peripheral blood mononuclear cells (PBMCs). Additionally, measurements of transepithelial electrical resistance (TEER) of TNF-α challenged Caco-2 cells co-incubated with the strains were performed to test the improvement of barrier function. We then used principal component analysis (PCA) to identify new strains with profiles similar to those of bacteria with proven probiotic effect [4], [5] [6] and found a promising strain called PI41. This strain was then tested in a rodent model of IBS induced by infection with Citrobacter rodentium[7]. After pathogen clearance (16 days post infection), mice were administered per os daily with PI41 or saline buffer for the control group. The PI41 strain was able to resolve colonic hypersensitivity as measured by colorectal distention (CRD) test. This result correlated with an increase of AhR agonists in mice feces. This strain is therefore promising as a new probiotic to prevent and treat IBS.