Abstract

Prediabetes (PreD) , which is associated with impaired glucose tolerance and fasting blood glucose, is a potential risk factor for type 2 diabetes mellitus (T2D) . Growing evidence suggests the role of the gastrointestinal microbiota in both PreD and T2D, which opens the possibility for a novel nutritional approach, based on probiotics, for improving glucose regulation and delaying disease progression of PreD to T2D. In this light, the present study aimed to assess the antidiabetic properties of Pediococcus acidilactici pA1c (pA1c) in a murine model of high-fat diet (HFD) -induced T2D. For that purpose, C57BL/6 mice were given HFD enriched with either probiotic (1×10E10 CFU/day) or placebo for 12 weeks. We determined body weight, fasting blood glucose, glucose tolerance, HOMA-IR and HOMA-β index, C-peptide, GLP-1, leptin, and lipid profile. We also measured hepatic gene expression (G6P, PEPCK, GCK, IL-1β, and IL-6) and ex-amined pancreatic and intestinal histology (% of GLP-1+ cells, % of goblet cells and villus length) . We found that pA1c supplementation significantly attenuated body weight gain, mitigated glucose dysregulation by reducing fasting blood glucose levels, glucose tolerance test, leptin levels, and insulin resistance, increased C-peptide and GLP-1 levels, enhanced pancreatic function, and improved intestinal histology. These findings indicate that pA1c improved HFD-induced T2D derived insulin resistance and intestinal histology, as well as protected from body weight increase. Together, our study proposes that pA1c may be a promising new dietary management strategy to improve metabolic disorders in PreD and T2D. Disclosure M. Cabello: None. M. Oneca: Employee; GENBIOMA APLICACIONES SL. M. J. Pajares: None. J. Ayo: Board Member; Genbioma Aplicaciones S. L., Employee; Genbioma Aplicaciones S. L. I. J. Encío: Other Relationship; Genbioma Aplicaciones SL. M. Araña: None. M. Barajas: None. Funding Government of Navarre (Ref 0011-1365-2020-000290) and the European Regional Development Fund (ERDF) . Maria Oneca is supported by Torres-Quevedo grants from the Spanish Ministry of Science and innovation (Ayudas para contratos Torres Quevedo PTQ2019-010384/AEI/10.13039/501100011033)

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