Probiotics are defined by the World Health Organization as live microorganisms which, when administered in adequate amounts, confer a health benefit on the host (1). Although their beneficial effects on health are proven, knowledge on their mechanisms of action is becoming a priority today. This is the case with L. rhamnosus Lcr35, whose probiotic and anti- Candida albicans properties have been demonstrated (2, 3). Lcr35 is genetically and physiologically well-characterized and it has been proven that ingredients included in the formulations is able to potentialize Lcr35 probiotic effect. In order to investigate the molecular mechanisms involved in the Lcr35 strain probiotic properties, in vivo studies have been carried out in C. elegans : the analysis of the nematode survival in the presence of the probiotic strain potentialized or not for the anti- C. albicans properties, and a preliminary analysis of the modulation of the immune response by Lcr35. The survival analyzes showed that the strain Lcr35 allowed a significant increased lifespan of the nematode in comparison with E. coli OP50 whereas C. albicans impaired survival. The activation of insulin and p38 MAPK pathways has been shown using RT-qPCR. Then we will go further into the investigations to understand the molecular mechanisms related to these properties by studying in particular the preventive and curative effects of Lcr35 with respect to a C. albicans infection. In addition, a complete analysis of the transcriptome of C. elegans will be carried out by RNA sequencing in order to precisely identify the signaling pathways involved in the interaction between the host and the probiotic or the pathogen microorganisms. Moreover, because of C. elegans genetic homology with humans and in particular its intestinal physiology close to humans, our work lead us to evaluate the potential of C. elegans to be a relevant in vivo model to characterize the molecular mechanisms involved in the probiotic potential of a microorganisms and then to screen microorganisms collections for their potential probiotic capacities. 1. FAO, WHO. 2001. Health and nutritional properties of probiotics in food including powder milk with live lactic acid bacteria. Food Nutr Pap 85:71. 2. Nivoliez A et al. 2012. Influence of manufacturing processes on in vitro properties of the probiotic strain Lactobacillus rhamnosus Lcr35. J Biotechnol 160:236–241. 3. Nivoliez A et al. 2015. Influence of manufacturing processes on cell surface properties of probiotic strain Lactobacillus rhamnosus Lcr35. Appl Microbiol Biotechnol 99:399–411