Background and Purpose: Obesity is a complex condition where a low-grade chronic inflammation and gut dysbiosis contribute to the development of the related metabolic dysfunctions. Nowadays, its management of such disease implies drastic changes in lifestyle and different anti-obesity drugs. Unfortunately, most of them present limited effectiveness and important side effects. Therefore there is an urgent demand for more effective and safer strategies for obesity management. In this sense, probiotics are emerging as a promising therapy. Different probiotics have demonstrated beneficial effects on this condition, increasing the interest in the development of probiotic treatments. Lactobacillus fermentum CECT5716 has shown anti-inflammatory effects and capacity to modulate microbiota composition in different experimental models. Experimental Approach: L. fermentum CECT5716 (5x10⁸ CFU/mice/day) was evaluated in a model of high fat diet-induced obesity in mice. Key results: L. fermentum exerts anti-obesity effects, associated with its anti-inflammatory properties and amelioration endothelial dysfunction and gut dysbiosis. The probiotic restores Akkermansia sp. abundance and reduced Erysipelotrichi class and Clostridium spp presence as well as increased Bacteroides proportion. Conclusion and Implications: This probiotic represents a very interesting approach. Our findings describe, for the first time, the ability of this probiotic to ameliorate experimental obesity through microbiome modulation, affecting different bacteria that have been reported to play a key role in the pathogenesis of obesity. Therefore, this suggests a potential use of L. fermentum CECT5716 in clinical practice, also taking into account that probiotic treatments have demonstrated to be relatively safe and well tolerated.