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Saccharomyces boulardii (S. boulardii) is a probiotic yeast that is widely used to treat gastrointestinal disorders. The present study is aimed to explore the therapeutic effects of S. boulardii on dextran sulfate sodium- (DSS-) induced murine ulcerative colitis (UC) and illustrate the mechanisms of action. C57BL/6 mice were administered S. boulardii (105 and 107 CFU/ml, p.o.) for 3 weeks and then given DSS [2.5% ( w / v )] for one week. Administration of S. boulardii prevented DSS-induced reduction in body weight, diarrhea, bloody feces, decreased colon length, and loss of histological structure. Moreover, S. boulardii protected the intestinal barrier by increasing the levels of tight junction proteins zona occludens-1 and Occludin and exerted immunomodulatory effects in DSS-induced mice. Furthermore, S. boulardii suppressed the colonic inflammation by reducing the levels of Interleukin-1β, Interleukin-6, and Tumor necrosis factor alpha and restored myeloperoxidase activity in mice exposed to DSS. S. boulardii also mitigated colonic oxidative damage by increasing the levels of antioxidant enzymes (superoxide dismutase, catalase, and heme oxygenase 1) and glutathione and decreasing malondialdehyde accumulation. Further studies identified that S. boulardii suppressed the nuclear translocation of nuclear factor kappa B (NF-κB) p65 subunit by decreasing IκKα/β levels, while promoted the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) in DSS-exposed mice. Collectively, S. boulardii possessed an appreciable therapeutic effect against the experimental mice model of UC. The protective mechanism of S. boulardii may involve inhibition of NF-κB-mediated proinflammatory signaling and activation of Nrf2-modulated antioxidant defense in addition to intestinal barrier protective and immunomodulatory effects.

Scope Several reports in the literature have suggested the renoprotective effects of ketone bodies and green tea polyphenols (GTPs). Our previous study found that GTP consumption could elevate the renal expression of the ketogenic rate-limiting enzyme, which was decreased by a high-fat diet (HFD) in rats. Here, we investigated whether ketogenesis can mediate renoprotection by GTPs against an HFD. Methods and Results Wistar rats were fed a standard or HFD with or without GTPs for 18 weeks. The renal oxidative stress level, kidney function, renal expression, and activity levels of mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase 2 (HMGCS2) and sirtuin 3(SIRT3) were detected. The increased renal oxidative stress and the loss of renal function induced by the HFD were ameliorated by GTPs. Renal ketogenesis and SIRT3 expression and activity levels, which were reduced by the HFD, were restored by GTPs. In vitro, HEK293 cells were transfected with the eukaryotic expression plasmid pcDNA HMGCS2. GTP treatment could upregulate HMGCS2 and SIRT3 expression. Although SIRT3 expression was not affected by HMGCS2 transfection, the 4-hydroxy-2-nonenal (4-HNE) level and the acetyl-MnSOD (K122)/MnSOD ratio were reduced in HMGCS2-transfected cells in the context of H2O2. Conclusion The ketogenesis/SIRT3 pathway mediates the renoprotection of GTPs against the oxidative stress induced by an HFD.