Summary: Recent studies highlighted the beneficial health effects of a supplementation with B. animalis subsp. lactis LA804 and L. gasseri LA806 strains, previously isolated by PiLeje Laboratoire. Thanks to a scientific collaboration, the DO-IT team provided its expertise to characterize the mechanism by which the mix of these two probiotics protects against weight gain and deterioration of lipid metabolism in mice fed a high-calorie diet. We demonstrated that the inhibition of the FXR nuclear receptor signaling pathway in the small intestine contributed to the beneficial effects of the probiotic intake, without altering intestinal permeability or short-chain fatty acid production. Our data suggest a new mechanism of action for probiotics at the intestinal level, opening the door to therapeutic or preventive strategies targeting FXR receptor activity in the management of weight and metabolic imbalances related to obesity or diabetes.