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other·endocrinology, nutrition, preclinical research, biomedical research, micronutrients·PMC10542285

Glucose-lowering effects of a synbiotic combination containing Pediococcus acidilactici in C. elegans and mice

Diabetologia · 7 authors, 5 centres

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TL;DR

The synbiotic combination improved glucose tolerance, reduced fasting blood glucose, and normalised liver steatosis in mice by modulating insulin–IGF-1 signalling, reducing proinflammatory cytokines, and altering gut microbiota composition.

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Caenorhabditis elegans was used as a complementary screening model. The synbiotic (pA1c+PC+BGC) additionally lowered fasting blood glucose, reduced visceral adiposity, increased muscle tissue proportion, and normalised hepatic steatosis versus the high-fat/sucrose group. Gene expression analyses indicated mediation through upregulation of GLUT-1, GLUT-4, Akt-1, and Insr alongside downregulation of Foxo-1, Pdk-4, and the proinflammatory cytokine MCP-1. Gut microbiota profiling revealed increases in P. acidilactici and Akkermansia muciniphila with the synbiotic. Limitations include the absence of human participants and the acknowledged non-complexity of C. elegans as a model organism.

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endocrinology

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ORIGINAL PAPER

PMC10542285

Glucose-lowering effects of a synbiotic combination containing Pediococcus acidilactici in C. elegans and mice

Diabetologia

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ABSTRACT

Aims/hypothesis 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. Methods 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 (10 10 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. Results 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 . Conclusions/interpretation 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. Graphical Abstract Supplementary Information The online version contains peer-reviewed but unedited supplementary material available at 10.1007/s00125-023-05981-w.

CITATION EXPORT

Deyan Yavorov-Dayliev, Fermín I. Milagro, Josune Ayo et al.. Glucose-lowering effects of a synbiotic combination containing Pediococcus acidilactici in C. elegans and mice. Diabetologia. (2023). https://doi.org/10.1007/s00125-023-05981-w

AUTHORS

7 · 5 CENTRES

Deyan Yavorov-Dayliev, Fermín I. Milagro, Josune Ayo, María Oneca, Ignacio Goyache, Miguel López-Yoldi, Paula Aranaz

1Genbioma Aplicaciones SL, Navarra, Spain
2https://ror.org/02rxc7m23grid.5924.a0000 0004 1937 0271Fac Pharm & Nutr, Dept Nutr Food Sci & Physiol, University of Navarra, Pamplona, Spain
3https://ror.org/02rxc7m23grid.5924.a0000 0004 1937 0271Center for Nutrition Research, University of Navarra, Pamplona, Spain
4grid.508840.10000 0004 7662 6114Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
5grid.413448.e0000 0000 9314 1427Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain