Type 1 diabetes mellitus (T1DM) is a disorder resulting from chronic autoimmune destruction of insulin-producing pancreatic β-cells, lack of insulin production and hyperglycaemia. The aim of this study was to evaluate the hypothesis that streptozotocin-diabetic mice treated with Saccharomyces boulardii THT 500101 strain present improvement of glucose and triglycerides metabolism, reduction of liver inflammation concomitant with a beneficial impact in the gut microbiota profile. C57BL/6 male mice were randomly assigned into three groups: Control, Diabetes, Diabetes+Probiotic, and were euthanised 8 weeks after probiotic chronic administration. Mice submitted to treatment presented reduced glycemia in comparison with the diabetic group, which was correlated with an increase in C-peptide level and in hepatic glycogen content. Fat metabolism was significantly altered in streptozotocin-induced diabetic group, and S. boulardii treatment regulated it, leading to a decrease in serum triglycerides secretion, increase in hepatic triglycerides storage and modulation of inflammatory profile. The phenotypic changes seen from chronic S. boulardii treatment were found to be broadly associated with the changes in microbioma of diabetic animals, with increased proportion in Bacteroidetes, Firmicutes and Deferribacteres, and a decreased proportion of Proteobacteria and Verrucomicrobia phylum. Thus, the data presented here show up a novel potential therapeutic role of S. boulardii for the treatment and attenuation of diabetes-induced complications.

Type 1 diabetes (T1DM) is a chronic disease characterized by hyperglycemia due to a deficiency in endogenous insulin production, resulting from pancreatic beta cell death. Persistent hyperglycemia leads to enhanced oxidative stress and liver injury. Several studies have evaluated the anti-diabetic and protective effects of probiotic strains in animal models. In the present study, we investigated, through histopathological and biochemical analyses, the effects of eight weeks of administration of Saccharomyces boulardii (S. boulardii) yeast on the liver of streptozotocin (STZ) induced diabetic C57BL/6 mice. Our results demonstrated that S. boulardii attenuates hepatocytes hydropic degeneration and hepatic vessels congestion in STZ-induced diabetic mice. The treatment attenuated the oxidative stress in diabetic mice leading to a reduction of carbonylated protein concentration and increased activity of antioxidant enzymes superoxide dismutase and glutathione peroxidase, compared to untreated diabetic animals. The results also show the beneficial influence of S. boulardii in regulating the hepatic concentration of renin angiotensin system (RAS) peptides. Therefore, our results demonstrated that S. boulardii administration to STZ-induced diabetic mice reduces oxidative stress and normalizes the concentration of RAS peptides, supporting the hypothesis that this yeast may have a role as a potential adjunctive therapy to attenuate diabetes-induced liver injury.

The effects of probiotics on blood glucose and cardiovascular complications induced by diabetes have been inconsistent. Therefore, the aim was to assess the effect of Saccharomyces boulardii (Sb) on metabolic and cardiovascular dysfunction in streptozotocin (STZ)-induced type-1-diabetes (STZ-T1D). Male C57BL/6 mice were randomized into: control (C), diabetes (D), control+Sb (CSb) and diabetes+Sb (DSb) (n=6-12/group). Mice were made diabetic with STZ (150mg/kg) and daily treated with Sb (0,5x108 CFU) by oral gavage. After 8 weeks of treatment, blood pressure (BP) and heart rate (HR) signals obtained from conscious mice were recorded. Spectral analysis of systolic BP (BPV) and HR variabilities (HRV) was performed to estimate autonomic modulation to the heart and vessels. Plasma was collected and heart was excised for biochemical analyses. D mice presented metabolic dysfunction, with increased blood glucose, triglycerides and cholesterol, as compared with C animals. On the other hand, treatment with Sb reduced blood glucose (DSb=238±39 vs. D=378±17 mg/dl) and triglycerides (DSb=121±11 vs. D=169±10 mg/dl), with no effect on cholesterol levels (DSb=119±4 vs. D=106±9 mg/dl). Probiotic treatment also reduced cardiac IL-6 (DSb=80±8 vs. D=113±13 pg/mg) and increased IL-10 (DSb=251±16 vs. D=185±11 pg/mg), leading to a beneficial impact on heart nitric oxide levels (DSb=12.4±1.3 vs. D=7.6±0.9 pg/mg). D mice presented a significant reduction in HRV, BPV and also in low-frequency component of systolic BP (SBP). Treatment of D mice with Sb increased HRV (DSb=20±0.9 vs. D=10±0.9 ms²), BPV (DSb=8±0.4 vs. D=5±0.3 mmHg²) and low-frequency component of SBP (DSb=98±8 vs. D=55±8 mmHg²). Our study shows, for the first time, that administration of Sb is strongly associated with glycemic control, cardiovascular protection and improvement of inflammatory profile in STZ-T1D. Disclosure A.B.P. Brandão: None. I.C. de Abreu: None. F. Aimbire: None. E.M. Higa: None. A. Casali: None. F.G. Ferreira: None. R.M. Albuquerque: None. L.B. Santos: None. M.C. Irigoyen: None. K.R. Casali: None. T.S. Cunha: None.

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

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