The increasing prevalence of metabolic syndrome-related diseases, including type-2 diabetes and obesity, makes it urgent to develop new alternative therapies, such as probiotics. In this study, we have used Caenorhabditis elegans under a high-glucose condition as a model to examine the potential probiotic activities of Pediococcus acidilactici CECT9879 (pA1c). The supplementation with pA1c reduced C. elegans fat accumulation in a nematode growth medium (NGM) and in a high-glucose (10 mM) NGM medium. Moreover, treatment with pA1c counteracted the effect of the high glucose by reducing reactive oxygen species by 20%, retarding the aging process and extending the nematode median survival (>2 days in comparison with untreated control worms). Gene expression analyses demonstrated that the probiotic metabolic syndrome-alleviating activities were mediated by modulation of the insulin/IGF-1 signaling pathway (IIS) through the reversion of the glucose-nuclear-localization of daf-16 and the overexpression of ins-6 and daf-16 mediators, increased expression of fatty acid (FA) peroxisomal β-oxidation genes, and downregulation of FA biosynthesis key genes. Taken together, our data suggest that pA1c could be considered a potential probiotic strain for the prevention of the metabolic syndrome-related disturbances and highlight the use of C. elegans as an appropriate in vivo model for the study of the mechanisms underlying these diseases.

Type 2 diabetes (T2D) is a complex metabolic disease, which involves maintained hyperglycemia, mainly due to the development of an insulin resistance process. Metformin administration is the most prescribed treatment for diabetic patients. In a previously published study, we demonstrated that Pediococcus acidilactici pA1c® (pA1c) protects from insulin resistance and body weight gain in HFD-induced diabetic mice. The present work aimed to evaluate the possible beneficial impact of a 16-week administration of pA1c, metformin, or the combination of pA1c and metformin in a T2D HFD-induced mice model. We found that the simultaneous administration of both products attenuated hyperglycemia, increased high-intensity insulin-positive areas in the pancreas and HOMA-β, decreased HOMA-IR and also provided more beneficial effects than metformin treatment (regarding HOMA-IR, serum C-peptide level, liver steatosis or hepatic Fasn expression), and pA1c treatment (regarding body weight or hepatic G6pase expression). The three treatments had a significant impact on fecal microbiota and led to differential composition of commensal bacterial populations. In conclusion, our findings suggest that P. acidilactici pA1c® administration improved metformin beneficial effects as a T2D treatment, and it would be a valuable therapeutic strategy to treat T2D.