Probiotic B420 and prebiotic polydextrose improve efficacy of antidiabetic drugs in mice

Diabetology & Metabolic Syndrome

Sampo Lahtinen²  Thierry Sulpice¹  Rémy Burcelin³  François Briand¹  Céline Garret³  Aurélie Waget³  Lotta K. Stenman² 

[1] Physiogenex SAS, Prologue Biotech, 516 Rue Pierre et Marie Curie, Labège Innopole, France;DuPont Nutrition and Health, Active Nutrition, Sokeritehtaantie 20, Kantvik, 02460, Finland;Institut des Maladies Métaboliques et Cardiovasculaires de Rangueil, Rangueil Hospital, INSERM1048, Toulouse, 31432, France

关键词: Sitagliptin;    Prebiotics;    Probiotics;    Metformin;    Mice;    Obesity;    Gastroenterology;    Diabetes;    Bifidobacteria;   

Others  :  1225018
DOI  :  10.1186/s13098-015-0075-7

 received in 2015-03-25, accepted in 2015-09-08,  发布年份 2015

【 摘 要 】

Background

Gut microbiota is now known to control glucose metabolism. Previous studies have shown that probiotics and prebiotics may improve glucose metabolism, but their effects have not been studied in combination with drug therapy. The aim of this study was to investigate whether probiotics and prebiotics combined with drug therapy affect diabetic outcomes.

Methods

Two different study designs were used to test gut microbiota modulating treatments with metformin (MET) or sitagliptin (SITA) in male C57Bl/6J mice. In Design 1, diabetes was induced with four-week feeding with a ketogenic, 72 kcal% fat diet with virtually no carbohydrates. Mice were then randomly divided into four groups (n = 10 in each group): (1) vehicle, (2) Bifidobacterium animalis ssp. lactis 420 (B420) (10 ⁹CFU/day), (3) MET (2 mg/mL in drinking water), or (4) MET + B420 (same doses as in the MET and B420 groups). After another 4 weeks, glucose metabolism was assessed with a glucose tolerance test. Fasting glucose, fasting insulin and HOMA-IR were also assessed. In Design 2, mice were fed the same 72 kcal% fat diet to induce diabetes, but they were simultaneously treated within their respective groups (n = 8 in each group): (1) non-diabetic healthy control, (2) vehicle, (3) SITA [3 mg/(kg*day)] (4) SITA with prebiotic polydextrose (PDX) (0.25 g/day), (5) SITA with B420 (10 ⁹CFU/day), and (6) SITA + PDX + B420. Glucose metabolism was assessed at 4 weeks, and weight development was monitored for 6 weeks.

Results

In Design 1, with low-dose metformin, mice treated with B420 had a significantly lower glycemic response (area under the curve) (factorial experiment, P = 0.002) and plasma glucose concentration (P = 0.02) compared to mice not treated with B420. In Design 2, SITA + PDX reduced glycaemia in the oral glucose tolerance test significantly more than SITA only (area under the curve reduced 28 %, P < 0.0001). In addition, B420, PDX or B420+PDX, together with SITA, further decreased fasting glucose concentrations compared to SITA only (−19.5, −40 and −49 %, respectively, P < 0.01 for each comparison). The effect of PDX may be due to its ability to increase portal vein GLP-1 concentrations together with SITA (P = 0.0001 compared to vehicle) whereas SITA alone had no statistically significant effect compared to vehicle (P = 0.14).

Conclusions

This study proposes that combining probiotics and/or prebiotics with antidiabetic drugs improves glycemic control and insulin sensitivity in mice. Mechanisms could be related to incretin secretion.

【 授权许可】

   
2015 Stenman et al.

【 图 表 】

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