The effect of a combination of metformin and the probiotic Enterococcus faecium L3 on glucose tolerance and its absorption in the small intestine in rats with type 2 diabetes mellitus

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A promising approach for the treatment of type 2 diabetes mellitus (T2DM) is the development of strategies that potentiate the effect of standard metformin therapy, including its combined use with probiotics that modulate the gut microbiota composition. The aim of this work was to study the effect of combined therapy with metformin and the probiotic Enterococcus faecium L3 on glycemia, insulin sensitivity, and the rate of glucose absorption in the small intestine in rats with experimental T2DM. Material and Methods. T2DM was induced in male Wistar rats by administering streptozotocin (30 mg/kg) after the animals consumed a high-fat diet for two months. Five rat groups were formed: control on a standard diet, T2DM without treatment, T2DM treated for 7 weeks with metformin (200 mg/kg/day), with the probiotic E. faecium L3 (108 CFU/day), and with their combination. Body weight and feed intake were assessed; an oral glucose tolerance test (OGTT) and an insulin tolerance test (ITT) were performed; and the rate of glucose absorption in the small intestine was determined. Results. Combined therapy with metformin and the probiotic E. faecium L3 demonstrated the highest efficacy. It reduced the area under the curve (AUC) in the OGTT by 47 % compared to the T2DM group, surpassing the effects of monotherapy with these agents. In the ITT, the combination of metformin and E. faecium L3, as well as E. faecium L3 monotherapy, enhanced glucose utilization at the 120-minute mark compared to the T2DM group. The most pronounced effect of the combined therapy was on the rate of glucose absorption in the small intestine, reducing it by 30–42 % compared to the T2DM group (p < 0.01), which exceeded the effects of monotherapy with these agents. Conclusions. The combined use of metformin and the probiotic E. faecium L3 has a synergistic effect, significantly improving glycemic control and reducing intestinal glucose absorption in rats with T2DM, which justifies the potential of choosing combined therapy with metformin and E. faecium L3 for the treatment of T2DM.

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