There is a growing need to develop new approaches to prevent and treat diseases related to metabolic syndromes, including obesity or type 2 diabetes, that focus on the different factors involved in the pathogenesis of these diseases. Due to the role of gut microbiota in the regulation of glucose and insulin homeostasis, probiotics with beneficial properties have emerged as an alternative therapeutic tool to ameliorate metabolic diseases-related disturbances, including fat excess or inflammation. In the last few years, different strains of bacteria, mainly lactic acid bacteria (LAB) and species from the genus Bifidobacterium, have emerged as potential probiotics due to their anti-obesogenic and/or anti-diabetic properties. However, in vivo studies are needed to demonstrate the mechanisms involved in these probiotic features. In this context, Caenorhabditis elegans has emerged as a very powerful simple in vivo model to study the physiological and molecular effects of probiotics with potential applications regarding the different pathologies of metabolic syndrome. This review aims to summarize the main studies describing anti-obesogenic, anti-diabetic, or anti-inflammatory properties of probiotics using C. elegans as an in vivo research model, as well as providing a description of the molecular mechanisms involved in these activities.

Probiotic strains with health-promoting activities have emerged as a promising strategy to prevent or treat different metabolic syndrome-related disturbances, including obesity or type 2 diabetes. In this work, we characterize the probiotic properties of a novel strain of Latilactobacillus sakei (L. sakei) CNTA 173, and we demonstrate its anti-obesity properties using the in vivo model Caenorhabditis elegans (C. elegans). This new strain exhibited sensitivity to the entire spectrum of antibiotics analysed, gastric and intestinal in vitro resistance, β-galactosidase activity, and the ability to form biofilm and to produce acetic acid in vitro. Cell culture analyses demonstrated that L. sakei CNTA 173 was able to reduce the adhesion to Caco-2 cells of the pathogenic E. coli O157:H7 and to exert immunomodulatory capacity in RAW 264.7 and HT-29 in vitro models. Furthermore, supplementation with L. sakei CNTA 173 counteracted the deleterious effects of glucose in C. elegans by significantly reducing fat accumulation, enhancing the oxidative stress response, and extending lifespan by directly regulating the carbohydrate and lipid metabolism-related genes acox-1, maoc-1, and daf-16. Our results unveil new strain-specific mechanisms of action by which L. sakei CNTA 173 exerts beneficial effects in vitro and in C. elegans, and suggest potential application of this novel probiotic strain in the prevention and treatment of metabolic syndrome-related disturbances.

The call for new approaches to prevent and treat metabolic syndrome-related diseases has led to research on the use of lacto-fermentative probiotics with beneficial metabolic properties like Lactobacilli. Here, we characterize the probiotic properties of a novel strain, Lactiplantibacillus plantarum CNTA 628, and investigate its potential anti-obesity and health-promoting activities in the Caenorhabditis elegans model, additionally elucidating the molecular mechanisms involved. Lactiplantibacillus plantarum CNTA 628 exhibited sensitivity to the entire spectrum of antibiotics analyzed, gastric and intestinal resistance in vitro, β-galactosidase and bile-salt hydrolysate activities, and the capacity to form biofilms and produce SCFAs. In addition, it reduced the binding of the pathogenic E. coli O157:H7 to intestinal epithelial cells (Caco-2) and exerted immune-modulating effects in cellular models. Supplementation with this probiotic significantly reduced C. elegans fat accumulation by more than 18% under control and high-glucose conditions, lowered senescence, improved oxidative stress, and significantly enhanced lifespan without affecting the development of the worms. Gene expression analyses evidenced that L. plantarum CNTA 628 plays a role in regulating daf-22 and maoc-1 gene expression, both linked to beta-oxidation pathways. Our results demonstrate the health-benefiting properties of this novel strain and suggest its potential as probiotic candidate for the prevention and treatment of metabolic syndrome-related conditions.

Introduction: In the last few years, several studies have described the beneficial effects of the supplementation of diets with certain probiotic strains and different obesity-related disturbances, including metabolic syndrome. New research lines aim to characterize and understand the strain-specific mechanisms of action and their effects on the host’s health. The use of animal models is necessary to understand how probiotics interact with the gut microbiota and exert beneficial activities, which would allow us gain insight into potential new strategies against obesity-related diseases. Objective: we aim to characterize the effects of a novel probiotic strain of Latilactobacillus sakei (L. sakei) in two different animal models with adiposity excess. Methods: Caenorhabditis elegans was used as a starting in vivo model to analyse how the probiotics affect fat accumulation, oxidative stress, senescence, and lifespan when exposed to high-glucose conditions. Then, the effects of L. sakei oral administration (10⁹ CFU/day) were evaluated in diet-induced obese (DIO) Wistar rats, and biochemical, transcriptomic, metagenomics, and metabolomics analyses were performed. Results: Supplementation with L. sakei in C. elegans counteracted the deleterious effects of glucose by reducing fat accumulation, enhancing the oxidative stress response, and extending lifespan by directly regulating the carbohydrate- and lipid metabolism-related genes acox-1, maoc-1, and daf-16. Following the same trend, DIO rats supplemented with L. sakei showed lower proportions of mesenteric and subcutaneous fat, improved glucose tolerance, and an ameliorated inflammatory marker profile, partly by regulating the expression levels of key metabolic genes like adiponectin, leptin, and Acox1. The oral administration of L. sakei modulated faecal microbiota composition and induced the production of novel plasma metabolites. Conclusions: our results unveil new strain-specific mechanisms of action through which L. sakei exerts health-promoting effects in C. elegans and DIO adiposity models, as well as further describe how these probiotics could potentially be useful for the prevention and treatment of metabolic syndrome-related diseases.