Intestinal microbiomics and liver metabolomics insights into the preventive effects of chromium (III)-enriched yeast on hyperlipidemia and hyperglycemia induced by high-fat and high-fructose diet.

In recent years, organic chromium (III) supplements have received increasing attentions for their low toxicity, high bioavailability and wide range of health-promoting benefits. This study aimed to investigate the preventive effects of chromium (III)-enriched yeast (YCr) on high-fat and high-fructose diet (HFHFD)-induced hyperlipidemia and hyperglycemia in mice, and further clarify its mechanism of action from the perspective of intestinal microbiomics and liver metabolomics. The results indicated that oral administration of YCr remarkably inhibited the aberrant elevations of body weight, blood glucose and lipid levels, hepatic cholesterol (TC) and triglyceride (TG) levels caused by HFHFD. Liver histological examination showed that oral YCr intervention inhibited HFHFD induced liver lipid accumulation. Besides, 16S rDNA amplicon sequencing showed that YCr intervention was beneficial to ameliorating intestinal microbiota dysbiosis by altering the proportion of some intestinal microbial phylotypes. Correlation-based network analysis indicated that the key intestinal microbial phylotypes intervened by YCr were closely related to some biochemical parameters associated with glucose and lipid metabolism. Liver metabolomics analysis revealed that dietary YCr intervention significantly regulated the levels of some biomarkers involved in purine metabolism, glycerophospholipid metabolism, citrate cycle, pyrimidine metabolism, glycerophospholipid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and so on. Moreover, dietary YCr intervention regulated the mRNA levels of key genes associated with glucose, cholesterol, fatty acids and bile acids metabolism in liver. These findings suggest that dietary YCr intervention has beneficial effects on glucose and lipid metabolism by regulating intestinal microbiota and liver metabolic pathway, and thus can be served as a functional component to prevent hyperlipidemia and hyperglycemia.

Organic chromium derived from the chelation of Ganoderma lucidum polysaccharide and chromium (III) alleviates metabolic syndromes and intestinal microbiota dysbiosis induced by high-fat and high-fructose diet.

Organic chromium is of great interest and has become an important chromium supplement resource in recent years because of its low toxicity and easy absorption. In our previous study, we synthesized a novel organic chromium [GLP-Cr] through the chelation of Ganoderma lucidum polysaccharide and chromium (III). The purpose of this study was to investigate the beneficial effects of GLP-Cr on the improvement of metabolic syndromes (MetS) in mice fed with a high-fat and high-fructose diet (HFHFD) and its mechanism of action. The results indicated that oral administration of GLP-Cr inhibited the excessive exaltation of body weight, glucose tolerance, fasting blood glucose and lipid levels, hepatic total cholesterol (TC), triglyceride (TG) levels caused by HFHFD. Besides, 16S rRNA amplicon sequencing showed that GLP-Cr intervention evidently ameliorated intestinal microbiota dysbiosis by changing the proportions of some intestinal microbial phylotypes. In addition, correlation network-based analysis indicated that the key intestinal microbial phylotypes were closely related to biochemical parameters associated with MetS under GLP-Cr intervention. Liver metabolomics analysis suggested that GLP-Cr intervention significantly regulated the levels of some biomarkers involved in alpha-linolenic acid metabolism, fatty acid biosynthesis, steroid hormone biosynthesis, glycerophospholipid metabolism, glycerolipid metabolism, steroid hormone biosynthesis, primary bile acid biosynthesis, and so on. Moreover, GLP-Cr intervention regulated liver mRNA levels of key genes associated with glucose and lipid metabolism. The mRNA level of glucose transporter type 4 (Glut4) was markedly increased by GLP-Cr intervention, and the mRNA levels of phosphoenolpyruvate carboxykinase (Pepck) and glucose-6-phosphatase (G6Pase) in the liver were significantly decreased. Meanwhile, GLP-Cr intervention significantly decreased hepatic mRNA levels of cluster of differentiation 36 (Cd36), acetyl-CoA carboxylase 1 (Acc1) and sterol regulatory element binding protein-1c (Srebp-1c), indicating that GLP-Cr intervention inhibited the excessive accumulation of free fatty acids in the liver. These findings suggest that the prevention of hyperglycemia and dyslipidemia by GLP-Cr may be closely related to the regulation of gut microbial composition and hepatic metabolic pathways, thus GLP-Cr can be serving as a functional component in the prevention of MetS.

Corrigendum to "Ganoderic acids-rich ethanol extract from Ganoderma lucidum protects against alcoholic liver injury and modulates intestinal microbiota in mice with excessive alcohol intake" [Curr. Res. Food Sci. 5(2022) 515-530].

[This corrects the article DOI: 10.1016/j.crfs.2022.02.013.].

Ganoderic acid A from Ganoderma lucidum protects against alcoholic liver injury through ameliorating the lipid metabolism and modulating the intestinal microbial composition.

Alcoholic liver injury is mainly caused by long-term excessive alcohol consumption and has become a global public threat to human health. It is well known that Ganoderma lucidum has excellent beneficial effects on liver function and lipid metabolism. The object of this study was to investigate the hepatoprotective effects of ganoderic acid A (GAA, one of the main triterpenoids in G. lucidum) against alcohol-induced liver injury and reveal the underlying mechanisms of its protective effects. The results showed that oral administration of GAA significantly inhibited the abnormal elevation of the liver index, serum total triglyceride (TG), cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in mice exposed to alcohol intake, and also significantly protected the liver against alcohol-induced excessive lipid accumulation and pathological changes. Besides, alcohol-induced oxidative stress in the liver was significantly ameliorated by the dietary intervention of GAA through decreasing the hepatic levels of lactate dehydrogenase (LDH) and malondialdehyde (MDA), and increasing hepatic activities of catalase (CAT), superoxide dismutase (SOD), alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and hepatic levels of glutathione (GSH). In addition, GAA intervention evidently ameliorated intestinal microbial disorder by markedly increasing the abundance of Muribaculaceae, Prevotellaceae, Jeotgalicoccus, Bilophila, Family_XIII_UCG_001, Aerococcus, Ruminococcaceae_UCG_005, Harryflintia, Christensenellaceae, Rumonpcpccaceae, Prevotelaceae_UCG_001, Clostridiales_vadinBB60_group, Parasutterella and Bifidobacterium, but decreasing the proportion of Lactobacillus, Burkholderia_Caballeroria_Paraburkholderia, Escherichia_Shigella and Erysipelatoclostridium. Furthermore, liver metabolomics based on UPLC-QTOF/MS demonstrated that oral administration of GAA had a significant regulatory effect on the composition of liver metabolites in mice exposed to alcohol intake, especially the levels of the biomarkers involved in the metabolic pathways of riboflavin metabolism, glycine, serine and threonine metabolism, pyruvate metabolism, glycolysis/gluconeogenesis, biosynthesis of unsaturated fatty acids, synthesis and degradation of ketone bodies, fructose and mannose metabolism. Moreover, dietary supplementation of GAA significantly regulated the hepatic mRNA levels of lipid metabolism and inflammatory response related genes. Conclusively, these findings demonstrate that GAA has beneficial effects on alleviating alcohol-induced liver injury and is expected to become a new functional food ingredient for the prevention of alcoholic liver injury.

Pediococcus acidilactici FZU106 alleviates high-fat diet-induced lipid metabolism disorder in association with the modulation of intestinal microbiota in hyperlipidemic rats.

Probiotics have been proved to have beneficial effects in improving hyperlipidemia. The purpose of the current research was to investigate the ameliorative effects of Pediococcus acidilactici FZU106, isolated from the traditional brewing of Hongqu rice wine, on lipid metabolism and intestinal microbiota in high-fat diet (HFD)-induced hyperlipidemic rats. Results showed that P. acidilactici FZU106 intervention obviously inhibited the abnormal increase of body weight, ameliorated serum and liver biochemical parameters related to lipid metabolism and oxidative stress. Histopathological evaluation also showed that P. acidilactici FZU106 could significantly reduce the excessive lipid accumulation in liver caused by HFD-feeding. Furthermore, P. acidilactici FZU106 intervention significantly increased the short-chain fatty acids (SCFAs) levels in HFD-fed rats, which was closely related to the changes of intestinal microbial composition and metabolism. Intestinal microbiota profiling by high-throughput sequencing demonstrated that P. acidilactici FZU106 intervention evidently increased the proportion of Butyricicoccus, Pediococcus, Rothia, Globicatella and [Eubacterium]_coprostanoligenes_group, and decreased the proportion of Corynebacterium_1, Psychrobacter, Oscillospira, Facklamia, Pseudogracilibacillus, Clostridium_innocuum_group, Enteractinococcus and Erysipelothrix in HFD-fed rats. Additionally, P. acidilactici FZU106 significantly regulated the mRNA levels of liver genes (including CD36, CYP7A1, SREBP-1c, BSEP, LDLr and HMGCR) involved in lipid metabolism and bile acid homeostasis. Therefore, these findings support the possibility that P. acidilactici FZU106 has the potential to reduce the disturbance of lipid metabolism by regulating intestinal microflora and liver gene expression profiles.

The Protective Effects of Ganoderic Acids from Ganoderma lucidum Fruiting Body on Alcoholic Liver Injury and Intestinal Microflora Disturbance in Mice with Excessive Alcohol Intake.

This study aimed to investigate the protective effects of ganoderic acids (GA) from Ganoderma lucidum against liver injury and intestinal microbial disorder in mice with excessive alcohol intake. Results showed GA supplement significantly inhibited the abnormal elevation of the liver index, serum lipid parameters, aspartate aminotransferase and alanine aminotransferase in mice exposed to alcohol intake, and also significantly protected the excessive lipid accumulation and pathological changes. Alcohol-induced oxidative stress in the liver was significantly ameliorated by GA intervention through reducing the levels of maleic dialdehyde and lactate dehydrogenase and increasing the levels of glutathione, catalase, superoxide dismutase and alcohol dehydrogenase. Intestinal microbiota profiling demonstrated GA intervention modulated the composition of intestinal microflora by increasing the levels of Lactobacillus, Faecalibaculum, Romboutsia, Bifidobacterium and decreasing the Helicobacter level. Furthermore, liver metabolomic profiling suggested GA intervention had a remarkable regulatory effect on liver metabolism with excessive alcohol consumption. Moreover, GA intervention regulated mRNA levels of alcohol metabolism, fatty lipid metabolism, oxidative stress, bile acid biosynthesis and metabolism-related genes in the liver. Conclusively, these findings demonstrate GA intervention can significantly relieve alcoholic liver injury and it is hopeful to become a new functional food ingredient for the prevention of alcoholic liver injury.

Ganoderic acids-rich ethanol extract from Ganoderma lucidum protects against alcoholic liver injury and modulates intestinal microbiota in mice with excessive alcohol intake.

Alcoholic liver injury is mainly caused by excessive alcohol consumption and has become a global public health problem threatening human health. It is well known that Ganoderma lucidum possesses various excellent beneficial effects on liver function and lipid metabolism. The purpose of this study was to evaluate the underlying protective effect and action mechanism of ganoderic acids-rich G. lucidum ethanol extract (GLE) on alcohol-induced liver injury in mice with excessive alcohol intake. Results showed that oral administration of GLE could obviously inhibit the abnormal increases of serum triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and also significantly protect the liver against alcohol-induced excessive hepatic lipid accumulation and pathological changes. In addition, alcohol-induced oxidative stress in liver was significantly ameliorated by the dietary intervention of GLE through reducing the hepatic levels of maleic dialdehyde (MDA) and lactate dehydrogenase (LDH), and increasing the hepatic levels of glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and alcohol dehydrogenase (ADH). Compared with the model group, GLE intervention significantly ameliorated the intestinal microbial disorder by elevating the relative abundance of Ruminiclostridium_9, Prevotellaceae_UCG-001, Oscillibacter, [Eubacterium]_xylanophilum_group, norank_f_Clostridiates_vadinBB60_group, GCA-900066225, Bilophila, Ruminococcaceae_UCG-009, norank_f_Desulfovibrionaceae and Hydrogenoanaerobacterium, but decreasing the proportion of Clostridium_sensu_stricto_1. Furthermore, liver metabolomic profiling suggested that GLE intervention had a significant regulatory effect on the composition of liver metabolites in mice with excessive alcohol intake, especially the levels of some biomarkers involved in primary bile acid biosynthesis, riboflavin metabolism, tryptophan metabolism, biosynthesis of unsaturated fatty acids, fructose and mannose metabolism, glycolysis/gluconeogenesis. Additionally, dietary supplementation with GLE significantly regulated the mRNA levels of key genes related to fatty acids metabolism, ethanol catabolism and inflammatory response in liver. Conclusively, these findings indicate that GLE has a potentially beneficial effect on alleviating alcohol-induced liver injury and may be developed as a promising functional food ingredient.

Potential mechanisms underlying the ameliorative effect of Lactobacillus paracasei FZU103 on the lipid metabolism in hyperlipidemic mice fed a high-fat diet.

Lactobacillus paracasei FZU103, a probiotic previously isolated from the traditional brewing process of Hongqu rice wine, may have the beneficial effect of improving the disorder of lipid metabolism. This study aimed to determine the beneficial effects of L. paracasei FZU103 on improving hepatic lipid accumulation associated with hyperlipidemia. Results indicated that L. paracasei FZU103 intervention significantly inhibited the abnormal growth of body weight and epididymal white adipose tissue (eWAT), prevented the hypertrophy of epididymal adipocytes, ameliorated the biochemical parameters of serum and liver related to lipid metabolism in HFD-fed mice. Histological analysis also showed that the excessive accumulation oflipid dropletsin the livers induced by HFD-feeding was greatly alleviated by L. paracasei FZU103 intervention. In addition, L. paracasei FZU103 also promoted the excretion of bile acids (BAs) through feces. Metagenomic analysis revealed that oral supplementation with L. paracasei FZU103 significantly increased the relative abundance of Ruminococcus, Alistipes, Pseudoflavonifractor and Helicobacter, but decreased the levels of Blautia, Staphylococcos and Tannerella in HFD-fed mice. The relationships between lipid metabolic parameters and intestinal microbial phylotypes were also revealed by correlation heatmap and network. Furthermore, ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS)-based liver metabolomics demonstrated that L. paracasei FZU103 had a significant regulatory effect on the metabolic pathways of glycerophospholipid metabolism, fatty acid degradation, fatty acid elongation, unsaturated fatty acids biosynthesis, riboflavin metabolism, glycerolipid metabolism, primary bile acid biosynthesis, arachidonic acid metabolism, etc. Additionally, L. paracasei FZU103 intervention regulated expression of hepatic genes involved in lipid metabolism and bile acid homeostasis, and promoted fecal excretion of intestinal BAs. These findings present new evidence supporting that L. paracasei FZU103 has the potential to improve lipid metabolism, and could be used as a potential functional food for the prevention of hyperlipidemia.

Monascus purpureus-fermented common buckwheat protects against dyslipidemia and non-alcoholic fatty liver disease through the regulation of liver metabolome and intestinal microbiome.

Monascus-fermented rice has been used to treat digestive disorder and promote blood circulation in China and other Asian countries for centuries. However, the effects and mechanisms of Monascus purpureus-fermented common buckwheat (HQ) on non-alcoholic fatty liver disease (NAFLD) and dyslipidemia are unclear. Here, oral supplementation of HQ significantly inhibited the abnormal growth of body weight and epididymal white adipose tissue (eWAT), prevented the hypertrophy of epididymal adipocytes, ameliorated some biochemical parameters of serum and liver related to lipid metabolism in mice fed a high-fat and high-cholesterol diet (HFD). Histological analysis also showed that the excessive accumulation of lipid droplets in the livers induced by HFD-feeding was greatly alleviated by HQ supplementation. Metagenomic analysis revealed that HQ supplementation made significant structural changes in the intestinal microflora of mice fed with HFD. The Spearman's correlation analysis revealed that physiological index, serum and liver lipid profiles were positively correlated with Bacteroidales S24-7, Streptococcus, Allobaculum, and Clostridiales XIII, but negatively associated with Lactobacillus, Ruminococcaceae_NK4A214 group, Ruminiclostridium, and Alistipes. UPLC-QTOF/MS-based liver metabolomics demonstrated that HQ intervention had significant regulatory effects on the metabolic pathways of primary bile acid biosynthesis, pyrimidine metabolism, ether lipid metabolism, glutathione metabolism, glycine, serine and threonine metabolism, and amino sugar and nucleotide sugar metabolism, etc. Additionally, HQ intervention regulated the mRNA levels of hepatic genes involved in hepatic lipid metabolism and bile acid homeostasis. Collectively, these findings present new evidence supporting that HQ has the potential to ameliorate dyslipidemia and NAFLD via modulating the intestinal microbial populations and hepatic metabolite profile in hyperlipidemic mice induced by HFD.

Ganoderic acid A from Ganoderma lucidum ameliorates lipid metabolism and alters gut microbiota composition in hyperlipidemic mice fed a high-fat diet.

Ganoderic acid A (GA) is one of the most abundant triterpenoids in Ganoderma lucidum, and has been proved to possess a wide range of beneficial health effects. The aim of the current study is to investigate the amelioration effects and mechanism of GA on improving hyperlipidemia in mice fed a high-fat diet (HFD). The results showed that GA intervention significantly inhibited the abnormal growth of body weight and epididymal white adipose tissue (eWAT), prevented the hypertrophy of epididymal adipocytes, and ameliorated the biochemical parameters of serum and liver related to lipid metabolism in HFD-fed mice. Histological analysis also showed that the excessive accumulation of lipid droplets in the liver induced by HFD-feeding was greatly alleviated by GA intervention. In addition, GA intervention also increased the level of short chain fatty acids (SCFAs) in the intestine and promoted the excretion of bile acids (BAs) through feces. High-throughput sequencing of bacterial full-length 16S rDNA revealed that daily supplementation with GA made significant structural changes in the gut microbial population of mice fed with HFD, in particular modulating the relative abundance of some function related microbial phylotypes. The relationships between lipid metabolic parameters and gut microbial phylotypes were also revealed by correlation analysis based on a heatmap and network. The result showed that 46 key gut microbial phylotypes (OTUs) were markedly correlated with at least one lipid metabolic parameter. Moreover, UPLC-QTOF/MS-based liver metabolomics showed that 111 biomarkers (47 up-regulated metabolites and 64 down-regulated metabolites) were significantly changed after high-dose GA intervention (75 mg kg-1 day-1), compared with the HFD-fed hyperlipidemic mice. Metabolic pathway enrichment analysis of the differential hepatic metabolites demonstrated that GA intervention had significant regulatory effects on primary bile acid biosynthesis, fatty acid biosynthesis, amino sugar and nucleotide sugar metabolism, inositol phosphate metabolism, and so on. In addition, GA intervention regulated the mRNA levels of hepatic genes involved in fatty acid metabolism and bile acid homeostasis. These findings present new evidence supporting that GA from G. lucidum has the potential to alleviate lipid metabolic disorders and ameliorate the imbalance of gut microflora in a positive way.

The protective mechanism of Lactobacillus plantarum FZU3013 against non-alcoholic fatty liver associated with hyperlipidemia in mice fed a high-fat diet.

Lactobacillus plantarum FZU3013, a probiotic previously isolated from the traditional brewing process of Hongqu rice wine, may have the beneficial effect of improving the disorders of lipid metabolism. This study aimed to investigate the role of L. plantarum FZU3013 in improving non-alcoholic fatty liver (NAFL) associated with hyperlipidemia in mice fed a high-fat diet. The results indicated that L. plantarum FZU3013 intervention significantly reduced the HFD-induced body weight gain and the abnormal levels of serum total triglycerides (TG), total cholesterol (TC) and low-density lipoprotein (LDL-C), and inhibited the excessive accumulation of liver lipids. In addition, L. plantarum FZU3013 also promoted the excretion of bile acids through feces. Metagenomic and multivariate statistical analysis revealed that L. plantarum FZU3013 made significant structural changes in the intestinal microbiome of the mice fed with HFD, in particular by modulating the relative abundance of some function related microbial phylotypes. Furthermore, ultra-performance liquid chromatography with quadruple-time of flight mass spectrometry (UPLC-QTOF/MS)-based liver metabolomics demonstrated that L. plantarum FZU3013 had a significant regulatory effect on the composition of liver metabolites in hyperlipidemic mice, especially on the levels of some important biomarkers involved in the pathways of glycerophospholipid metabolism, fatty acid degradation, fatty acid elongation, glycerolipid metabolism, primary bile acid biosynthesis, arachidonic acid metabolism, etc. Moreover, L. plantarum FZU3013 regulated the mRNA expression levels of the genes responsible for liver lipid and cholesterol metabolism. L. plantarum FZU3013 intervention increased the hepatic mRNA levels of cholesterol 7α-hydroxylase (CYP7A1) and the bile salt export pump (BSEP), suggesting enhanced bile acid synthesis and excretion from the liver. These findings present new evidence supporting that L. plantarum FZU3013 has the potential to improve lipid metabolism disorders through modulating specific intestinal microbial phylotypes and regulating hepatic lipid metabolism related genes, therefore it could be used as a potential functional food for the prevention of NAFL and hyperlipidemia.

The protective mechanisms of macroalgae Laminaria japonica consumption against lipid metabolism disorders in high-fat diet-induced hyperlipidemic rats.

Macroalgae Laminaria japonica (MLJ) has been reported to exhibit various biological activities including improving immunity, anti-aging, anti-tumor, anti-atherosclerosis and anti-diabetic, but the protective mechanisms of MLJ consumption against non-alcoholic fatty liver disease (NAFLD) associated with hyperlipidemia remain poorly understood. This study demonstrated that MLJ consumption prevented high-fat diet (HFD)-induced NAFLD associated with hyperlipidemia in a rat model, and improved hyperlipidemia-related parameters, e.g. serum and hepatic lipid profiles. Moreover, histological analysis showed that MLJ reduced lipid deposition in adipocytes and hepatocytes compared with the HFD group. Such beneficial effects may be associated with the modulation of the intestinal microbiota, especially some key microbial phylotypes involved in lipid metabolism homeostasis. The underlying protective mechanisms of MLJ consumption against HFD-induced NAFLD associated with hyperlipidemia were also studied by ultra-high performance liquid chromatography with quadruple-time of flight mass spectrometry (UPLC-QTOF/MS)-based liver metabolomics coupled with pathway analysis. The metabolic pathway enrichment analysis of the differentially abundant hepatic metabolites indicated that primary bile acid biosynthesis metabolism and cysteine and methionine metabolism were the two main metabolic pathways altered by MLJ consumption when compared with the model group. The analysis of the transcription levels of liver-related genes by RT-qPCR and the expressions of liver-related proteins by immunohistochemistry (IHC) showed that MLJ consumption could regulate the levels of mRNA transcription and protein expression related to hepatic lipid metabolism. In short, this study indicates that MLJ could be developed as functional food supplement for the prevention or treatment of NAFLD associated with hyperlipidemia.

Hypoglycemic and hypolipidemic mechanism of organic chromium derived from chelation of Grifola frondosa polysaccharide-chromium (III) and its modulation of intestinal microflora in high fat-diet and STZ-induced diabetic mice.

Polysaccharide from Grifola frondosa is an excellent metal-ion chelating agent owing to its distinctive structure and outstanding functional activities. Our previous research has successfully synthesized novel organic chromium derived from the chelation ofG. frondosapolysaccharide-chromium (III) [GFP-Cr(III)]. The purpose of present research was to reveal the hypoglycemic and hypolipidemic mechanism of GFP-Cr(III), and its relationship with the modulation of intestinal microflora. Successful fabrication of GFP-Cr(III) was verified by thermogravimetric analysis (TGA), powder X-ray diffraction (XRD) and 1H NMR spectrum.The hypoglycemic and hypolipidemic effects were examined using type 2 diabetic mice induced by a high-fat diet (HFD) and streptozocin (STZ). Results indicated that GFP-Cr(III) intervention improved abnormal serum biochemical indicators (triglyceride (TG), cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and glucose), inhibited lipid accumulation and steatosis in the liver. Metagenomic analysis revealed that GFP-Cr(III) treatment produced obvious changes on the intestinal microflora in T2DM mice. Thecorrelationnetwork analysis further revealed that the serum and hepatic lipid profiles were positively correlated with Streptococcus and Enterococcus, but negatively correlated with Enterorhabdus, Ruminococcaceae-UCG-011, Coriobacteriaceae and Micrococcaceae. Meanwhile, oral administration with GFP-Cr(III) regulated the mRNA expression related to glucose and lipid metabolism. These results of present study suggest that GFP-Cr(III) could be used as potential functional food ingredients for the amelioration of hyperglycemia and hyperlipidemia.

Hypoglycemic and hypolipidemic activities of Grifola frondosa polysaccharides and their relationships with the modulation of intestinal microflora in diabetic mice induced by high-fat diet and streptozotocin.

This study aimed to investigate the hypoglycemic and hypolipidemic activities of polysaccharides from Grifola frondosa (GFP) in diabetic mice induced by high-fat diet (HFD) and streptozotocin (STZ). Results showed that oral administration of GFP markedly reduced the serum levels of fasting blood glucose (FBG), oral glucose tolerance (OGT), cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), and significantly decreased the hepatic levels of TC, TG and free fatty acids (FFA). Meanwhile, high-dose of GFP supplementation (900 mg/kg day) also showed powerful effects on moderating the composition of intestinal microflora in diabetic mice, especially altering the functionally relevant intestinal microbial phylotypes. Spearman's correlation network analysis revealed that key microbial phylotypes responding to GFP intervention were strongly correlated with the glucose and lipid metabolic disorders associated parameters. Moreover, GFP treatment regulated mRNA expression levels of the genes responsible for hepatic glucose and lipid metabolism. It is noteworthy that GFP treatment markedly increased mRNA expression of cholesterol 7α-hydroxylase (CYP7A1) and bile salt export pump (BSEP), suggesting an enhancement of bile acids (BAs) synthesis and excretion in liver. These findings demonstrated that GFP could prevent hyperglycemia and hyperlipidemia in diabetic mice by altering gut microbiota and regulating hepatic glycolipid metabolism related genes, and therefore could be used as potential functional food ingredients for the prevention or treatment of hyperglycemia and hyperlipidemia.

Preparation of Ganoderma lucidum polysaccharide­chromium (III) complex and its hypoglycemic and hypolipidemic activities in high-fat and high-fructose diet-induced pre-diabetic mice.

Polysaccharide from Ganoderma lucidum is one of the best metal-ion chelating agents because of its structural characteristics and excellent functional activities. In this study, we synthesized and characterized a novel G. lucidum polysaccharide­chromium (III) [GLP-Cr(III)] complex. Response surface methodology (RSM) was used to optimize the reaction conditions for the maximum chelation rate of GLP-Cr(III) complex. The optimal reaction conditions obtained from RSM were as follows: concentration of CrCl3 5.71 mg/mL, pH 6.36, temperature 66.4 °C and time 2.0 h, respectively. The pH was the most significant factor, followed by reaction temperature and CrCl3 concentration. Under the optimal conditions, the experimental chelation rate was 94.17 ±â€¯1.0% for GLP-Cr(III) complex, which agreed closely with the predicted value (94.60%). Fourier transform infrared (FT-IR) spectroscopy revealed that the primary sites of chromium (III)-binding in G. lucidum polysaccharide were OH and CO groups, which induce the morphology change from flat sheet to rough surface. Meanwhile, according to the result of X-ray diffraction (XRD), the crystal degree of GLP was disappeared after chelation with Cr(III). The presence of a "blind zone" in the 1H NMR spectrum obviously indicated the binding of Cr(III) to GLP. Additionally, the effects of GLP-Cr(III) complex on hyperglycemia and hyperlipidemia in high fructose and fat diet-induced pre-diabetic mice were also investigated. Results showed that the serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), fasting blood glucose levels and glucose tolerance in mice supplemented with GLP-Cr(III) complex (50 mg/kg day) were significantly lower than the model group (P < 0.01). More importantly, the GLP-Cr(III) complex had no significant adverse effects on the physiological metabolism, organ index, and liver tissue morphology of mice fed a normal diet. These results suggest that GLP-Cr(III) complex could be used as potential functional food ingredients for the prevention or treatment of hyperglycemia and hyperlipidemia.

Microbial communities and volatile metabolites in different traditional fermentation starters used for Hong Qu glutinous rice wine.

Hong Qu glutinous rice wine (HQGRW), as one of the most typical representatives of Chinese rice wine, is generally brewed from glutinous rice by adding two traditional wine fermentation starters-Hong Qu (HQ) and Bai Qu (BQ). The objective of this study was to determine the microbial communities and volatile metabolites of different traditional fermentation starters for HQGRW, and elucidate the potential correlation between microbiota and volatile metabolites. Both heatmap and principal component analysis (PCA) revealed the significant variances in volatile profiles among different wine starters. Microbiological analysis based on high-throughput sequencing (HTS) technology demonstrated that both of bacterial and fungal communities varied significantly in different starters. HQ was dominated mainly by bacteria of Bacillus ginsengihumi (20.17%), Pantoea sp. (10.39%), Elizabethkingia sp. (5.52%), Streptococcus sp. (5.03%) Brevundimonas sp. (3.03%), Rickettsia prowazekii (2.94%), Thermus thermophilus (2.54%), Bacillus amyloliquefaciens (1.48%), Bacillus aryabhattai (1.42%); fungi of Monascus purpureus (39.7%), Aspergillus niger (27.35%), Xeromyces bisporus (8.39%), Aspergillus penicillioides (6.89%), Aspergillus flavus (2.33%) and Pichia farinose (0.79%). By contrast, BQ contained much higher proportions of bacteria of Lactococcus lactis (10.45%), Lactobacillus brevis (9.99%), Pediococcus pentosaceus (8.29%), Weissella paramesenteroides (6.69%), Lactobacillus fermentum (4.83%), Gluconobacter thailandicus (3.93%), Lactobacillus alimentarius (3.59%), fungi of Rhizopus arrhizus (31.47%), Saccharomycopsis fibuligera (27.86%), Aspergillus niger (20.81%), Issatchenkia orientalis (3.79%), Saccharomycopsis malanga (3.15%), Clavispora lusitaniae (2.29%), Candida tropicalis (1.47%), Saccharomyces cerevisiae (1.11%) and Rhizopus microsporus (0.57%). Furthermore, core functional microbiota that might contribute to volatile flavour development was explored through Spearman's correlation-based network analysis. Lactobacillus brevis, Lactobacillus alimentarius, Lactobacillus plantarum and Aspergillus niger were found to be strongly associated with acid compounds (FDR adjusted P < 0.01), while Pichia sp., Candida sp., Monascus purpureus, Lactobacillus brevis and Lactobacillus alimentarius were positively correlated with concentrations of aromatic esters associated with fruity and floral notes (FDR adjusted P < 0.01), implying that these microorganisms might make significant contributions to the flavour of rice wine. These findings demonstrated that the aromatic quality of HQGRW may be critically influenced by the microbiota in traditional fermentation starters. To conclude, this study would contribute to the development of novel defined starter cultures for improving the aromatic quality of HQGRW.

Grifola frondosa polysaccharides ameliorate lipid metabolic disorders and gut microbiota dysbiosis in high-fat diet fed rats.

The purpose of this study was to assess the potential effects of polysaccharides from edible mushroom Grifola frondosa (GFP) on lipid metabolic disorders and gut microbiota dysbiosis, and elucidate their possible regulatory mechanisms on lipid and cholesterol metabolism in high-fat diet (HFD)-exacerbated hyperlipidemic and hypercholesterolemic rats. Results showed that oral administration of GFP markedly alleviated dyslipidaemia through decreasing the serum levels of total triglycerides, total cholesterol, and free fatty acids, and significantly suppressing hepatic lipid accumulation and steatosis. Besides, the excretion of fecal bile acids was also promoted by oral administration of GFP. Metagenomic analysis revealed that GFP supplementation (400 mg kg-1 day-1) resulted in significant structure changes on gut microbiota in HFD-fed rats, in particular modulating the relative abundance of functionally relevant microbial phylotypes compared with the HFD group. Key microbial phylotypes responding to GFP intervention were identified to strongly correlate with the lipid metabolism disorder associated parameters using the correlation network based on Spearman's correlation coefficient. Serum and hepatic lipid profiles were found positively correlated with Clostridium-XVIII, Butyricicoccus and Turicibacter, but negatively correlated with Helicobater, Intestinimonas, Barnesiella, Parasutterella, Ruminococcus and Flavonifracter. Moreover, GFP treatment (400 mg kg-1 day-1) regulated the mRNA expression levels of the genes responsible for hepatic lipid and cholesterol metabolism. Oral supplementation of GFP markedly increased the mRNA expression of cholesterol 7α-hydroxylase (CYP7A1) and bile salt export pump (BSEP), suggesting an enhancement of bile acid (BA) synthesis and excretion from the liver. These findings illustrated that GFP could ameliorate lipid metabolic disorders through modulating specific gut microbial phylotypes and regulating hepatic lipid and cholesterol metabolism related genes, and therefore could be used as a potential functional food ingredient for the prevention or treatment of hyperlipidemia.

Preparation of a novel Grifola frondosa polysaccharide-chromium (III) complex and its hypoglycemic and hypolipidemic activities in high fat diet and streptozotocin-induced diabetic mice.

Polysaccharide from Grifola frondosa is one of the best metal-ion chelating agents because of its structural characteristics and excellent functional activities. In this study, we synthesized and characterized a novel Grifola frondosa polysaccharide-chromium (III) [GFP-Cr(III)] complex. Response surface methodology (RSM) was used to optimize the reaction conditions for the maximum chelation rate of GFP-Cr(III) complex. The optimal reaction conditions obtained from RSM were as follows: concentration of CrCl3 6.97 mg/mL, pH 7.75 and temperature 71.73 °C, respectively. The pH was the most significant factor, followed by reaction temperature and concentration of CrCl3. Under the deduced optimal conditions (CrCl3 7.0 mg/mL, pH 7.7 and temperature 70.0 °C), the experimental chelation rate was 28.01% ±â€¯0.18% for GFP-Cr(III) complex, which agreed closely with the predicted value (27.61%). Fourier transform infrared (FTIR) spectroscopy revealed that the primary sites of chromium (III)-binding in polysaccharides were OH and CN groups, leading to the structure of GFP-Cr(III) complex was loose than the original polysaccharide. Nevertheless, Cr(III) did not make a fundamental change in the structure of GFP when comparing the FTIR spectra of GFP and GFP-Cr(III) complex. Additionally, the effects of GFP-Cr(III) complex on hyperglycemia and hyperlipidemia in high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic mice were also investigated. Results showed that the serum total cholesterol (TC), total triglyceride (TG), low density lipoprotein cholesterol (LDL-C), fasting blood glucose levels and glucose tolerance in diabetic mice fed a high-fat diet (HFD) supplemented with GFP-Cr(III) complex (900 mg/kg day) were significantly lower than the diabetic group (P < 0.01). These results suggest that GFP-Cr(III) complex could be used as potential functional food ingredients for the prevention or treatment of hyperglycemia and hyperlipidemia.

Effect of Grifola frondosa 95% ethanol extract on lipid metabolism and gut microbiota composition in high-fat diet-fed rats.

This study aimed to investigate the effects of 95% ethanol extract of G. frondosa (GF95) on lipid metabolism and gut microbiota composition in high-fat diet (HFD) fed rats. UPLC/Q-TOF MS indicated that GF95 was enriched with flavones, fatty acids and so on. Meanwhile, we found that body weight, serum lipid or liver index (total cholesterol, triglyceride, and low density lipoprotein cholesterol) levels were significantly decreased in GF95-treated HFD-fed rats. Furthermore, GF95 treatment regulated mRNA expression levels involved in lipid metabolism. GF95 consumption significantly enhanced the excretion of bile acids in the cecum. Besides, in this study, a higher abundance of Butyricimonas genus was revealed in the GF95 group, which is highly related to the highest production of short-chain fatty acids in the caecum contents among the experimental groups. Interestingly, results from network analysis showed that Butyricimonas were negatively correlated with serum and liver lipid profiles.

Exploring core functional microbiota responsible for the production of volatile flavour during the traditional brewing of Wuyi Hong Qu glutinous rice wine.

The objective of this study was to explore the core functional microbiota for the production of volatile flavour during the traditional brewing of Wuyi Hong Qu glutinous rice wine, one of the most typical representatives of rice wine in China. Microbiological analysis based on high-throughput sequencing (HTS) technology demonstrated that bacteria of Lactobacillus, Bacillus, Leuconostoc, Lactococcus, Raoultella, Staphylococcus, Pediococcus, and Weissella, and fungi of Saccharomyces, Saccharomycopsis, Rhizopus, Monascus, Pichia, Wickerhamomyces, Candida, and Aspergillus were the predominant genera during the traditional fermentation process. Principal component analysis (PCA) based on the relative abundance showed that both of bacterial and fungal communities varied significantly in different fermentation phases. Some predominant microbial species or genera (including bacteria of Bacillus spp., Staphylococcus spp., Weissella spp., and P. acidilactici, and fungi of M. purpureus, R. oryzae, R. arrhizus var. arrhizus, and A. niger) were detected at the initial brewing stage, and their populations decreased as the fermentation progressed, while those of Lactobacillus, Gluconacetobacter, Leuconostoc, Pichia, Wickerhamomyces, and Saccharomyces increased to become the predominant genera at the final stage. A total of 79 volatile compounds were identified in traditional fermentation starters and during the traditional brewing process, mainly including esters, alcohols, acids, aldehydes, ketones, and phenols. Heatmaps and PCA also revealed the significant variances in the composition of volatile compounds among different samples. Furthermore, the potential correlations between microbiota succession and volatile flavour dynamics were explored through bidirectional orthogonal partial least squares (O2PLS) based correlation analysis. Three bacterial genera, namely, Gluconacetobacter, Lactobacillus, Lactococcus, and three fungal genera of Pichia, Wickerhamomyces, and Saccharomyces, were determined as the core functional microbiota for production of main volatile compounds in Wuyi Hong Qu glutinous rice wine. To conclude, information provided by this study is valuable to the development of effective strategies for the selection of beneficial bacterial and fungal strains to improve the quality of Wuyi Hong Qu glutinous rice wine.