Saccharomyces boulardii protects against murine experimental colitis by reshaping the gut microbiome and its metabolic profile.

Introduction: Saccharomyces boulardii (S. boulardii) has shown clinical beneficial effect in inflammatory bowel diseases recently. However, the underlying mechanisms remain incompletely understood. The aim of present study was to tested whether S. boulardii targets gut microbiota to protect against the development of experimental colitis in mice. Methods: Female C57BL/6 mice were gavaged with S. boulardii for 3 weeks before being challenged with dextran sulphate sodium to induce ulcerative colitis. Bodyweight, diarrhea severity, intestinal permeability, colonic histopathology, colonic inflammatory status, and epithelial cell death of mice were examined. The fecal microbiota and its metabolomic profiles were detected by 16S rDNA sequencing and UPLC-MS, respectively. Results and Discussion: Supplementation with S. boulardii significantly prevented weight loss and colon shortening, lowered colonic inflammation, ameliorated epithelial injury, and enhanced the intestinal barrier integrity in colitis mice. By inhibiting the abundance of pathogenic bacteria and increasing the probiotics abundance, S. boulardii improved the microbial diversity and restored the microbiota dysbiosis. Moreover, it also modulated microbial metabolome and altered the relative contents of metabolites involving amino acids, lipids, energy and vitamin metabolisms. These yeast-driven shifts in gut flora and metabolites are were associated with each other and with the inflammation profile in colitis. Collectively, S. boulardii exerts protective effects on colitis in mice by reshaping gut microbiome and its metabolic profile, indicating it as a promising therapeutic avenue.

Dietary condition and feeding practices of children aged 6-23 months in Ethiopia: analysis of 2005-2016 demographic and health survey.

BACKGROUND: Childhood malnutrition is well estimated as the major underlying risk factor for morbidity and mortality in children under 5 years. Feeding practices greatly influence the dietary condition of children aged 6-23 months in developing countries. Therefore, this study was performed to determine the association between infant young children feeding (IYCF) practices and the dietary conditions of children aged 6-23 months in Ethiopia. METHOD: A cross-sectional study was conducted based on data on 5638 children aged 6-23 months from three Ethiopia Demographic and Health Surveys (EDHS) (2005, 2011, 2016). Multivariable logistic regression was performed to estimate the odd ratios (ORs) and 95% confidence intervals (CIs) of stunting and anaemia with IYCF practices. RESULT: The prevalence of stunting among children aged 6-23 months in Ethiopia decreased greatly from 49% in 2005 to 32% in 2016. Among the IYCF practices, consumption of iron-rich foods, minimum dietary diversity (MDD), and minimum acceptable diet (MAD) were significant predictors of stunting. In addition, the prevalence of anaemia declined significantly from 26% in 2005 to 16% in 2011, but increased to 29% in 2016. Among the IYCF practices, breastfeeding and minimum meal frequency (MMF) had lower odds of childhood anaemia. CONCLUSIONS: The present study showed that anaemia and stunting among children aged 6-23 months in Ethiopia is critical public health problems that need urgent attention.

Green Tea Polyphenols Ameliorate the Early Renal Damage Induced by a High-Fat Diet via Ketogenesis/SIRT3 Pathway.

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.

Green Tea Polyphenols, Mimicking the Effects of Dietary Restriction, Ameliorate High-Fat Diet-Induced Kidney Injury via Regulating Autophagy Flux.

Epidemiological and experimental studies reveal that Western dietary patterns contribute to chronic kidney disease, whereas dietary restriction (DR) or dietary polyphenols such as green tea polyphenols (GTPs) can ameliorate the progression of kidney injury. This study aimed to investigate the renal protective effects of GTPs and explore the underlying mechanisms. Sixty Wistar rats were randomly divided into 6 groups: standard diet (STD), DR, high-fat diet (HFD), and three diets plus 200 mg/kg(bw)/day GTPs, respectively. After 18 weeks, HFD group exhibited renal injuries by increased serum cystatin C levels and urinary N-acetyl-ß-d-glucosaminidase activity, which can be ameliorated by GTPs. Meanwhile, autophagy impairment as denoted by autophagy-lysosome related proteins, including LC3-II, Beclin-1, p62, cathepsin B, cathepsin D and LAMP-1, was observed in HFD group, whereas DR or GTPs promoted renal autophagy activities and GTPs ameliorated HFD-induced autophagy impairment. In vitro, autophagy flux suppression was detected in palmitic acid (PA)-treated human proximal tubular epithelial cells (HK-2), which was ameliorated by epigallocatechin-3-gallate (EGCG). Furthermore, GTPs (or EGCG) elevated phosphorylation of AMP-activated protein kinase in the kidneys of HFD-treated rats and in PA-treated HK-2 cells. These findings revealed that GTPs mimic the effects of DR to induce autophagy and exert a renal protective effect by alleviating HFD-induced autophagy suppression.

Comparative Study on Trace Element Excretions between Nonanuric and Anuric Patients Undergoing Continuous Ambulatory Peritoneal Dialysis.

Few studies have been reported on alterations of trace elements (TE) in peritoneal dialysis patients. Our objective was to investigate and assess the characteristics of daily TE excretions in continuous ambulatory peritoneal dialysis (CAPD) patients. This cross-sectional study included 61 CAPD patients (nonanuric/anuric: 45/16) and 11 healthy subjects in Wuhan, China between 2013 and 2014. The dialysate and urine of patients and urine of healthy subjects were collected. The concentrations of copper (Cu), zinc (Zn), selenium (Se), molybdenum (Mo), and arsenic (As) in dialysate and urine were determined using inductively coupled plasma mass spectrometer (ICP-MS). Various clinical variables were obtained from automatic biochemical analyzer. Daily Cu, Zn, Se, and Mo excretions in nonanuric patients were higher than healthy subjects, while arsenic excretion in anuric patients was lower. A strong and positive correlation was observed between Se and Mo excretion in both dialysate (ß = 0.869, p < 0.010) and urine (ß = 0.968, p < 0.010). Furthermore, the clinical variables associated with Se excretion were found to be correlated with Mo excretion. Our findings indicated that nonanuric CAPD patients may suffer from deficiency of some essential TEs, while anuric patients are at risk of arsenic accumulation. A close association between Se and Mo excretion was also found.

Tea polyphenols alleviate high fat and high glucose-induced endothelial hyperpermeability by attenuating ROS production via NADPH oxidase pathway.

BACKGROUND: Hyperglycemia-induced endothelial hyperpermeability is crucial to cardiovascular disorders and macro-vascular complications in diabetes mellitus. The objective of this study is to investigate the effects of green tea polyphenols (GTPs) on endothelial hyperpermeability and the role of nicotinamide adenine dinucleotide phosphate (NADPH) pathway. METHODS: Male Wistar rats fed on a high fat diet (HF) were treated with GTPs (0, 0.8, 1.6, 3.2 g/L in drinking water) for 26 weeks. Bovine aortic endothelial cells (BAECs) were treated with high glucose (HG, 33 mmol/L) and GTPs (0.0, 0.4, or 4 µg/mL) for 24 hours in vitro. The endothelial permeabilities in rat aorta and monolayer BAECs were measured by Evans blue injection method and efflux of fluorescein isothiocyanate (FITC)-dextran, respectively. The reactive oxygen species (ROS) levels in rat aorta and monolayer BAECs were measured by dihydroethidium (DHE) and 2', 7'-dichloro-fluorescein diacetate (DCFH-DA) fluorescent probe, respectively. Protein levels of NADPH oxidase subunits were determined by Western-blot. RESULTS: HF diet-fed increased the endothelial permeability and ROS levels in rat aorta while HG treatments increased the endothelial permeability and ROS levels in cultured BAECs. Co-treatment with GTPs alleviated those changes both in vivo and in vitro. In in vitro studies, GTPs treatments protected against the HG-induced over-expressions of p22phox and p67phox. Diphenylene iodonium chloride (DPI), an inhibitor of NADPH oxidase, alleviated the hyperpermeability induced by HG. CONCLUSIONS: GTPs could alleviate endothelial hyperpermeabilities in HF diet-fed rat aorta and in HG treated BAECs. The decrease of ROS production resulting from down-regulation of NADPH oxidase contributed to the alleviation of endothelial hyperpermeability.

Green tea polyphenols inhibit plasminogen activator inhibitor-1 expression and secretion in endothelial cells.

Compelling epidemiological evidence suggests that the consumption of green tea is associated with beneficial effects in prevention of cardiovascular diseases. Plasminogen activator inhibitor-1 (PAI-1) is known to play a pivotal role in cardiovascular diseases including arteriosclerosis and hypertension. Increased PAI-1 was found in atherosclerotic lesions, and high PAI-1 plasma levels were associated with coronary heart disease. To determine the effect and molecular mechanism of green tea polyphenols (GTPs) on the regulation of PAI-1 expression in endothelial cells, bovine aortic endothelial cells were incubated with GTPs, and PAI-1 expressions were measured by western blot and enzyme-linked immunosorbent assay, respectively. GTPs significantly reduced PAI-1 expression and secretion in a time-dependent and dose-dependent manner. Inhibition of phosphatidylinositol 3-kinase (PI3K) with wortmannin markedly reversed GTPs repression of PAI-1 expression. In addition, the GTP-induced inhibitory effect was associated with an increased of activation of the protein kinase Akt. These results suggest that GTPs inhibit PAI-1 expression and its release from endothelial cells through the PI3K/Akt pathway, which may contribute to cardiovascular protection.

Green tea polyphenols down-regulate caveolin-1 expression via ERK1/2 and p38MAPK in endothelial cells.

Caveolin-1 (Cav-1), a negative regulator of endothelial nitric oxide synthase (eNOS), influences various aspects of the cardiovascular functions. We had reported that a high-fat diet up-regulated aortic Cav-1 expressions in rats. In this study, we investigated the effects of green tea polyphenols (GTPs) on endothelial Cav-1 expression and phosphorylation in vitro. Bovine aortic endothelial cells (BAECs) were treated with 4 microg/ml GTPs for 0, 4, 8, 12, 16 and 24 h, and with 0, 0.04, 0.4, 4 and 40 microg/ml GTPs for 16 h, respectively. Cav-1 protein and mRNA were detected using Western blot and reverse transcriptase polymerase chain reaction. Cav-1 protein expression was down-regulated after treatment of BAECs with 4 microg/ml GTPs for 12, 16 and 24 h. And decrease in the level of Cav-1 mRNA was observed after GTP treatment for 4 and 8 h. GTPs (0.04-4 microg/ml) down-regulate Cav-1 protein expressions and mRNA levels dose dependently. PD98059, an inhibitor of extracellular signal-regulated kinase 1/2 (ERK1/2), up-regulated Cav-1 expression in BAECs alone and abolished the down-regulation effects of GTPs in BAECs while pretreatment with it. Inhibition of p38 mitogen-activated protein kinase (p38MAPK) with SB203580, which down-regulates Cav-1 expression in BAECs alone, deteriorated the Cav-1 down-regulating effects by GTPs. In addition to the effects on expression of Cav-1, GTP treatment inhibited phosphorylation of Cav-1 [tyrosine 14 (Tyr14)]. These data indicate that GTPs down-regulate gene expression of Cav-1 time- and dose- dependently via activating ERK1/2 and inhibiting p38MAPK signaling.

ROS-related enzyme expressions in endothelial cells regulated by tea polyphenols.

OBJECTIVE: Elevation of reactive oxygen species (ROS), especially the level of superoxide is a key event in many forms of cardiovascular diseases. To study the mechanism of tea polyphenols against cardiovascular diseases, we observed the expressions of ROS-related enzymes in endothelial cells. METHODS: Tea polyphenols were co-incubated with bovine carotid artery endothelial cells (BCAECs) in vitro and intracellular NADPH oxidase subunits p22phox and p67phox, SOD-1, and catalase protein were detected using Western blot method. RESULTS: Tea polyphenols of 0.4 microg/mL and 4.0 microg/mL (from either green tea or black tea) down-regulated NADPH oxidase p22phox and p67phox expressions in a dose-negative manner (P < 0.05), and up-regulated the expressions of catalase (P < 0.05). CONCLUSIONS: Tea polyphenols regulate the enzymes involved in ROS production and elimination in endothelial cells, and may be beneficial to the prevention of endothelial cell dysfunction and the development of cardiovascular diseases.