Background and Purpose: Melatonin has shown beneficial effects on obesity, both in humans and experimental models, via regulating the altered circadian rhythm and thus ameliorating the gut dysbiosis associated with this metabolic condition. However, its clinical use is limited, mostly due to its short half-life. Agomelatine is an agonist of the melatonin receptors that could be used to manage obesity and offer a better profile than melatonin. Experimental Approach: Male C57BL/6 mice were fed a high fat diet and orally treated for five weeks with agomelatine, or melatonin or metformin, used as control drugs. Metabolic profile, inflammatory status, vascular dysfunction and intestinal microbiota composition were assessed. Key Results: Agomelatine lessened body weight gain, enhanced glucose and lipid metabolisms, and improved insulin resistance. It also reduced the obesity-associated inflammatory status and endothelial dysfunction, probably linked to its effect on gut dysbiosis, consisting of the restoration of bacterial populations with key functions, such as short chain fatty acid production. Conclusions and Implications: Agomelatine can be considered as a novel therapeutic tool for the management of human obesity and its associated comorbidities.

Background and Purpose: Colorectal cancer (CRC) is one of the cancers with the highest incidence in which APC gene mutations occurs in almost 80% of patients. This mutation leads to β-catenin aberrant accumulation and an uncontrolled proliferation. Apoptosis evasion, changes in the immune response and microbiota composition are also events that arise in CRC. Tetracyclines are drugs with proven antibiotic and immunomodulatory properties that have shown cytotoxic activity against different tumor cell lines. Experimental Approach: The effect of tigecycline was evaluated in vitro in HCT116 cells and in vivo in a colitis-associated colorectal cancer (CAC) murine model. 5-fluorouracil was assayed as positive control in both studies. Key Results: Tigecycline showed an antiproliferative activity targeting the Wnt/β-catenin pathway and downregulating STAT3. Moreover, tigecycline induced apoptosis through extrinsic, intrinsic and endoplasmic reticulum pathways converging on an increase of CASP7 levels. Furthermore, tigecycline modulated the immune response in CAC, reducing the cancer-associated inflammation through a downregulation of cytokines expression. Additionally, tigecycline favored the cytotoxic activity of CD8+ T lymphocytes, one of the main immune defenses against tumor cells. Lastly, the antibiotic reestablished the gut dysbiosis in CAC mice increasing the abundance of bacterial genera and species, such as Akkermansia and Parabacteroides distasonis, that act as protectors against tumor development. These findings resulted in a reduction of the numbers of tumors and an amelioration of the tumorigenesis process in CAC. Conclusion and Implications: tigecycline exerts a beneficial effect against CRC supporting the use of this antibiotic for the treatment of this disease.

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.