Pediococcus acidilactici pA1c((R)) Improves the Beneficial Effects of Metformin Treatment in Type 2 Diabetes by Controlling Glycaemia and Modulating Intestinal Microbiota

Type 2 diabetes (T2D) is a complex metabolic disease, which involves maintained hyperglycemia, mainly due to the development of an insulin resistance process. Metformin administration is the most prescribed treatment for diabetic patients. In a previously published study, we demonstrated that Pediococcus acidilactici pA1c (R) (pA1c) protects from insulin resistance and body weight gain in HFD-induced diabetic mice. The present work aimed to evaluate the possible beneficial impact of a 16-week administration of pA1c, metformin, or the combination of pA1c and metformin in a T2D HFD-induced mice model. We found that the simultaneous administration of both products attenuated hyperglycemia, increased high-intensity insulin-positive areas in the pancreas and HOMA-beta, decreased HOMA-IR and also provided more beneficial effects than metformin treatment (regarding HOMA-IR, serum C-peptide level, liver steatosis or hepatic Fasn expression), and pA1c treatment (regarding body weight or hepatic G6pase expression). The three treatments had a significant impact on fecal microbiota and led to differential composition of commensal bacterial populations. In conclusion, our findings suggest that P. acidilactici pA1c (R) administration improved metformin beneficial effects as a T2D treatment, and it would be a valuable therapeutic strategy to treat T2D.