CECT9879

Gestational diabetes mellitus (GDM) is the most common complication of pregnancy and is known to be associated with an increased risk of postpartum metabolic disease. Based on the important role that the intestinal microbiota plays in blood glucose regulation and insulin sensitivity, supplementation of probiotic and postbiotic strains could improve glucose metabolism and tolerance in GDM.

56 4-week-old female C57BL/6J-mice were divided into 4 groups (n = 14 animals/group): control (CNT), high-fat/high-sucrose (HFS), pA1c® alive (pA1c®) and heat-inactivated pA1c® (pA1c®HI). Serum biochemical parameters were analyzed, gene expression analyses were conducted, and fecal microbiota composition was evaluated by shot-gun sequencing.

pA1c®- and pA1c® HI-supplemented groups presented reduced fasting blood glucose levels and reduced insulin resistance during gestation and exhibited lower visceral adiposity and increased muscle tissue, together with an improvement in intrahepatic TGs content and ALT levels. Liver gene expression analyses demonstrated that pA1c® and pA1c® HI activities were mediated by modulation of the insulin receptor, but also by an overexpression of beta-oxidation genes, and downregulation of fatty acid biosynthesis genes. Shot-gun metagenomics demonstrated that Pediococcus acidilactici was detected in the feces of all the pA1c® and pA1c® HI-group after the supplementation period (75 % of the microbial profile was Pediococcus acidilactici) in only nine weeks of supplementation, and modulated gut microbiota composition.

These results may be considered as future perspectives for the development of preventive, even therapeutic options for GDM based on hyperglycemia reduction, blood glucose regulation, hepatic steatosis attenuation and insulin resistance alleviation.

Modulation of gut microbiota has emerged as a promising strategy to treat or prevent the development of different metabolic diseases, including type 2 diabetes and obesity. Previous data from our group suggest that the strain Pediococcus acidilactici CECT9879 (pA1c) could be an effective probiotic for regulating glucose metabolism. Hence, the objectives of this study were to verify the effectiveness of pA1c on glycaemic regulation in diet-induced obese mice and to evaluate whether the combination of pA1c with other normoglycaemic ingredients, such as chromium picolinate (PC) and oat β-glucans (BGC), could increase the efficacy of this probiotic on the regulation of glucose and lipid metabolism.

Caenorhabditis elegans was used as a screening model to describe the potential synbiotic activities, together with the underlying mechanisms of action. In addition, 4-week-old male C57BL/6J mice were fed with a high-fat/high-sucrose diet (HFS) for 6 weeks to induce hyperglycaemia and obesity. Mice were then divided into eight groups (n=12 mice/group) according to dietary supplementation: control-diet group; HFS group; pA1c group (10¹⁰ colony-forming units/day); PC; BGC; pA1c+PC+BGC; pA1c+PC; and pA1c+BGC. Supplementations were maintained for 10 weeks. Fasting blood glucose was determined and an IPGTT was performed prior to euthanasia. Fat depots, liver and other organs were weighed, and serum biochemical variables were analysed. Gene expression analyses were conducted by real-time quantitative PCR. Sequencing of the V3-V4 region of the 16S rRNA gene from faecal samples of each group was performed, and differential abundance for family, genera and species was analysed by ALDEx2R package.

Supplementation with the synbiotic (pA1c+PC+BGC) counteracted the effect of the high glucose by modulating the insulin-IGF-1 signalling pathway in C. elegans, through the reversal of the glucose nuclear localisation of daf-16. In diet-induced obese mice, all groups supplemented with the probiotic significantly ameliorated glucose tolerance after an IPGTT, demonstrating the glycaemia-regulating effect of pA1c. Further, mice supplemented with pA1c+PC+BGC exhibited lower fasting blood glucose, a reduced proportion of visceral adiposity and a higher proportion of muscle tissue, together with an improvement in the brown adipose tissue in comparison with the HFS group. Besides, the effect of the HFS diet on steatosis and liver damage was normalised by the synbiotic. Gene expression analyses demonstrated that the synbiotic activity was mediated not only by modulation of the insulin-IGF-1 signalling pathway, through the overexpression of GLUT-1 and GLUT-4 mediators, but also by a decreased expression of proinflammatory cytokines such as monocyte chemotactic protein-1. 16S metagenomics demonstrated that the synbiotic combinations allowed an increase in the concentration of P. acidilactici, together with improvements in the intestinal microbiota such as a reduction in Prevotella and an increase in Akkermansia muciniphila.

Our data suggest that the combination of pA1c with PC and BGC could be a potential synbiotic for blood glucose regulation and may help to fight insulin resistance, diabetes and obesity.