Pediococcus acidilactici CECT9879 (pA1c) Counteracts the Effect of a High-Glucose Exposure in C. elegans by Affecting the Insulin Signaling Pathway (IIS)

Abstract

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.

Gut microbiota and obesity: New insights

“…Furthermore, some specific bacterial species are associated with a lower level of insulin resistance in the context of obesity. In a nematode, the supplementation with Pediococcus acidilactici neutralized the effect of high glucose levels, apparently by modulation of the insulin/IGF-1 signaling pathway (51). Similarly, in obese and lean Asian subjects, a negative correlation has been found between the intestinal abundance of Akkermansia muciniphila and the risk of increased severity of insulin resistance (52).…”

Pediococcus acidilactici (pA1c®) alleviates obesity-related dyslipidemia and inflammation in Wistar rats by activating beta-oxidation and modulating the gut microbiota

“…54 Hence, these findings support the anti-lipogenic role of pA1c® in the liver of individuals with obesity and are in agreement with previous studies conducted by our group on C. elegans and mice. 23,55…”

“…Importantly, this rise in beta-oxidation, together with the overexpression of the glucose metabolism genes Slc2a1 and Slc2a4, is in concordance with our previous studies on C. elegans and mice, where we demonstrated that the mechanism of action of pA1c® affected the insulin signalling and beta-oxidation pathways. 23,55 Looking more closely at Fig. 2B reveals a downregulation of perilipin-1 (Plin-1), which is a gene that encodes lipid droplet surface proteins named perilipins, in the pA1c® rats compared with the HFS rats.…”

“…Previous studies of our group demonstrated that pA1c® was able to regulate the lipid and carbohydrate metabolism in C. elegans through the modulation of the insulin signalling pathway. 23 Moreover, the probiotic strain pA1c® was able to regulate glucose metabolism in diabetic mice. 24 Bearing this in mind, and with the goal of continuing to explore the metabolic activities of pA1c®, we administered this probiotic strain to male Wistar rats fed an obesogenic diet, which mimics three important obesity-related disturbances, namely, fat accumulation, dyslipidemia and inflammation.…”

Application of Caenorhabditis elegans in Lipid Metabolism Research

“…An enhanced ROS production can inhibit insulin signaling and then activated daf-16 stimulates the expression of fat-5 , ultimately leading to an excessive fat accumulation [ 101 ]. The gene expression analysis demonstrated that Pediococcus acidilactici CECT9879 (pA1c) could alleviate the metabolic syndrome by reversing the glucose-nuclear-localization of daf-16 , overexpressing ins-6 , daf-2 , or ageing alteration-1 ( age-1 ), and downregulating the key genes for the biosynthesis of FAs [ 102 ]. Xiong et al found that Fuzhuan Tea relied on the regulation of the expression of fat-7 by DAF-16/FoxO to reduce the adiposity in C. elegans on glucose-rich diets [ 103 ].…”