Hypoglycemic effect and hepato protective role of Saccharomyces boulardii THT 500101 strain in a murine model of streptozotocin‐induced diabetes

The chronic hyperglycemia of diabetes mellitus (DM) is associated with long‐term damage and dysfunction of different organs, including the liver. Hyperglycemia induces hepatic mitochondrial dysfunction causing changes that include decreased oxidative phosphorylation, increased oxidative stress, ultra‐structural abnormalities, which in turn worse metabolic health. The disturbance in metabolic homeostasis also modulates gut microbiota by a variety of mechanisms while the maintenance of intestinal microbiota has a significant influence on metabolic state. The aim of this study was to evaluate the hypothesis that streptozotocin‐diabetic mice treated with Saccharomyces boulardii THT 500101 strain ( S. boulardii , THT: Probiotics and Starters Cultures, Belgium) present improvement of blood glucose, reduction of oxidative stress and maintenance of hepatocytes structure, concomitant with a beneficial impact in the gut microbiota profile. C57BL/6 male mice were randomly assigned into four groups: Control (C), Control + Probiotic (CP), Diabetes (D), and Diabetes + Probiotic (DP) (n = 9/group). Diabetic mice treated with S. boulardii presented a reduction of blood glucose (~30%) when compared to D group (DP = 251.9 ± 36.40 mg/dl vs. D = 362.9 ± 21.26 mg/dl, p<0.05). D group presented a higher level of carbonylated proteins compared with C and CP groups (C = 3.26 ± 0.42, CP = 3.00 ± 0.37 vs . D = 3.62 ± 0.33 nmol/mg), and probiotics reduced hepatic protein damage in DP (DP = 3.29 ± 0.58 nmol/mg). Diabetes reduced the activity of antioxidant enzymes superoxide dismutase (SOD) (D = 8.00 ± 0.12 vs. C = 8.49 ± 0.10, CP = 8.44 ± 0.05 USOD/mg, p<0.05) and glutathione peroxidase (GPx) (D = 73.50 ± 9.50 vs. C = 83.00 ± 4.00, CP = 81.00 ± 7.25 nmol/min/mg, p<0.05) and S. boulardii increased the activity of both enzymes in DP group as compared with D (SOD: DP =8.20 ± 0.14 USOD/mg and GPx: DP = 5.08 ± 2.29 nmol/mg, p<0.05). Signs of severe hydropic degeneration were noticed in hepatocytes from D group and to a lesser extent in hepatocytes from DP group. S. boulardii treatment was associated with increased proportion in Bacteroidetes, Firmicutes and Deferribacteres , and a decreased proportion of Proteobacteria and Verrucomicrobia phylum in DP group, as compared with D. Thus, the data presented here show up a novel potential therapeutic role of S. boulardii for glycemic control and attenuation of diabetes‐induced liver injury. Support or Funding Information FAPESP 2016/24059‐2