Protective effect of agaro-oligosaccharides on gut dysbiosis and colon tumorigenesis in high-fat diet-fed mice

High-fat diet (HFD)-induced alteration in the gut microbial composition, known as dysbiosis, is increasingly recognized as a major risk factor for various diseases, including colon cancer. This report describes a comprehensive investigation of the effect of agaro-oligosaccharides (AGO) on HFD-induced gut dysbiosis, including alterations in short-chain fatty acid contents and bile acid metabolism in mice. C57BL/6N mice were fed a control diet or HFD, with or without AGO. Terminal restriction fragment-length polymorphism (T-RFLP) analysis produced their fecal microbiota profiles. Profiles of cecal organic acids and serum bile acids were determined, respectively, using HPLC and liquid chromatography-tandem mass spectrometry systems. T-RFLP analyses showed that an HFD changed the gut microbiota significantly. Changes in the microbiota composition induced by an HFD were characterized by a decrease in the order Lactobacillales and by an increase in the Clostridium subcluster XIVa. These changes of the microbiota community generated by HFD treatment were suppressed by AGO supplementation. As supported by the data of the proportion of Lactobacillales order, the concentration of lactic acid increased in the HFD + AGO group. Data from the serum bile acid profile showed that the level of deoxycholic acid, a carcinogenic secondary bile acid produced by gut bacteria, was increased in HFD-receiving mice. The upregulation tended to be suppressed by AGO supplementation. Finally, results show that AGO supplementation suppressed the azoxymethane-induced generation of aberrant crypt foci in the colon derived from HFD-treated mice. Our results suggest that oral intake of AGO prevents HFD-induced gut dysbiosis, thereby inhibiting colon carcinogenesis.

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Yeast β-glucan reduces obesity-associated Bilophila abundance and modulates bile acid metabolism in healthy and high-fat diet mouse models

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00226.2021 ◽

2021 ◽

Author(s):

Sik Yu So ◽

Qinglong Wu ◽

Kin Sum Leung ◽

Zuzanna Maria Kundi ◽

Tor C Savidge ◽

...

Keyword(s):

Bile Acid ◽

Gut Microbiota ◽

High Fat Diet ◽

Metabolic Health ◽

Metabolic Phenotype ◽

Bile Acid Metabolism ◽

Microbiota Composition ◽

High Fat ◽

Mrna Accumulation ◽

Gut Microbiota Composition

Emerging evidence links dietary fiber with altered gut microbiota composition and bile acid signaling in maintaining metabolic health. Yeast β-glucan (Y-BG) is a dietary supplement known for its immunomodulatory effect, yet its impact on the gut microbiota and bile acid composition remains unclear. This study investigated whether dietary forms of Y-BG modulate these gut-derived signals. We performed 4-week dietary supplementation in healthy mice to evaluate effects of different fiber composition (soluble vs particulate Y-BG) and dose (0.1 vs. 2%). We found that 2% particulate Y-BG induced robust gut microbiota community shifts with elevated liver Cyp7a1 mRNA abundance and bile acid synthesis. These diet-induced responses were notably different when compared to the prebiotic inulin, and included a marked reduction in fecal Bilophila abundance which we demonstrated as translatable to obesity in population-scale American Gut and TwinsUK clinical cohorts. This prompted us to test whether 2% Y-BG maintained metabolic health in mice fed 60% HFD over 13 weeks. Y-BG consistently altered the gut microbiota composition and reduced Bilophila abundance, with trends observed in improvement of metabolic phenotype. Notably, Y-BG improved insulin sensitization and this was associated with enhanced ileal Glpr1r mRNA accumulation and reduced Bilophila abundance. Collectively, our results demonstrate that Y-BG modulates gut microbiota community composition and bile acid signaling, but the dietary regime needs to be optimized to facilitate clinical improvement in metabolic phenotype in an aggressive high-fat diet animal model.

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Estradiol treatment or modest exercise improves hepatic health and mitochondrial outcomes in female mice following ovariectomy

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00013.2021 ◽

2021 ◽

Author(s):

Kelly N. Z. Fuller ◽

Colin S. McCoin ◽

Alex T. Von Schulze ◽

Claire J. Houchen ◽

Michael A. Choi ◽

...

Keyword(s):

Bile Acid ◽

Mitochondrial Function ◽

High Fat Diet ◽

Acid Metabolism ◽

Bile Acid Metabolism ◽

High Fat ◽

Estradiol Treatment ◽

Respiratory Capacity ◽

Female Mice ◽

Mitochondrial Respiratory

We recently reported that compared to males, female mice have increased hepatic mitochondrial respiratory capacity and are protected against high-fat diet-induced steatosis. Here we sought to determine the role of estrogen in hepatic mitochondrial function, steatosis, and bile acid metabolism in female mice, as well as investigate potential benefits of exercise in the absence or presence of estrogen via ovariectomy (OVX). Female C57BL mice (n=6 per group) were randomly assigned to sham surgery (Sham), ovariectomy (OVX), or OVX plus estradiol replacement therapy (OVX+Est). Half of the mice in each treatment group were sedentary (SED) or had access to voluntary wheel running (VWR). All mice were fed a high-fat diet (HFD) and were housed at thermoneutral temperatures. We assessed isolated hepatic mitochondrial respiratory capacity using the Oroboros O2k with both pyruvate and palmitoylcarnitine as substrates. As expected, OVX mice presented with greater hepatic steatosis, weight gain, and fat mass gain compared to Sham and OVX+Est animals. Hepatic mitochondrial coupling (Basal/State 3 respiration) with pyruvate was impaired following OVX, but both VWR and estradiol treatment rescued coupling to levels greater than or equal to Sham animals. Estradiol and exercise also had different effects on liver electron transport chain protein expression depending on OVX status. Markers of bile acid metabolism and excretion were also impaired by ovariectomy but rescued with estradiol add-back. Together our data suggest that estrogen depletion impairs hepatic mitochondrial function and liver health, and that estradiol replacement and modest exercise can aid in rescuing this phenotype.

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Hypocholesterolaemic effect of whole-grain highland hull-less barley in rats fed a high-fat diet

British Journal Of Nutrition ◽

10.1017/s0007114518000831 ◽

2018 ◽

Vol 119 (10) ◽

pp. 1102-1110 ◽

Cited By ~ 8

Author(s):

Xuejuan Xia ◽

Guannan Li ◽

Jiaxin Song ◽

Jiong Zheng ◽

Jianquan Kan

Keyword(s):

Bile Acid ◽

High Fat Diet ◽

Control Diet ◽

Ldl Receptor ◽

Acid Synthesis ◽

Farnesoid X Receptor ◽

High Dose ◽

Whole Grain ◽

Sprague Dawley ◽

High Fat

AbstractWhole-grain highland hull-less barley (WHLB) contains high amounts of bioactive compounds that potentially exhibit cholesterol-lowering effects. This study investigated the hypocholesterolaemic effect of WHLB. A total of seventy-two male Sprague–Dawley rats were divided into four groups and were fed with the normal control diet, high-fat diet (HFD) and HFD containing low or high dose (10 or 48·95 %) of WHLB. High dose of WHLB significantly decreased the organ indexes of liver and abdominal fat and lipid levels of plasma and liver in HFD rats. The lipid regulation effect of WHLB, which was reconfirmed through hepatocyte morphologic observation, was accompanied by a large excretion of bile acids in the small intestinal contents and the faeces. Real-time PCR analyses, which were further reconfirmed through Western blot analyses, revealed that a high dose of WHLB significantly enhanced the hepatic expressions of AMP-activated protein kinase α, cholesterol 7α-hydroxylase, LDL receptor, liver X receptor, and PPARα and decreased the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase. It also enhanced the ileal expression of farnesoid X receptor and resulted in the decrease of expression of apical sodium-dependent bile acid transporter. WHLB exhibited hypocholesterolaemic effects mainly by inhibiting cholesterol synthesis, cholesterol accumulation in peripheral tissue, and bile acid reabsorption and by stimulating bile acid synthesis.

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Gender-divergent expression of lipid and bile acid metabolism-related genes in adult mice offspring of dams fed a high-fat diet

Journal of Biosciences ◽

10.1007/s12038-018-9750-9 ◽

2018 ◽

Vol 43 (2) ◽

pp. 329-337 ◽

Cited By ~ 6

Author(s):

Yuji Tanaka ◽

Takanori Ikeda ◽

Kazuo Yamamoto ◽

Shiori Masuda ◽

Hiroshi Ogawa ◽

...

Keyword(s):

Bile Acid ◽

High Fat Diet ◽

Acid Metabolism ◽

Bile Acid Metabolism ◽

High Fat ◽

Adult Mice

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A sulfated polysaccharide from Gracilaria Lemaneiformis regulates cholesterol and bile acid metabolism in high-fat diet mice

Food & Function ◽

10.1039/c9fo00263d ◽

2019 ◽

Vol 10 (6) ◽

pp. 3224-3236 ◽

Cited By ~ 14

Author(s):

Shiming Huang ◽

Daorui Pang ◽

Xiong Li ◽

Lijun You ◽

Zhengang Zhao ◽

...

Keyword(s):

Lipid Metabolism ◽

Bile Acid ◽

High Fat Diet ◽

Acid Metabolism ◽

Sulfated Polysaccharide ◽

Gracilaria Lemaneiformis ◽

Bile Acid Metabolism ◽

High Fat

This study aimed to evaluate the regulation of lipid metabolism and mechanism of a sulfated polysaccharide from Gracilaria Lemaneiformis (GLP).

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Alteration of Bile Acid Metabolism by a High-Fat Diet Is Associated with Plasma Transaminase Activities and Glucose Intolerance in Rats

Journal of Nutritional Science and Vitaminology ◽

10.3177/jnsv.65.45 ◽

2019 ◽

Vol 65 (1) ◽

pp. 45-51 ◽

Cited By ~ 3

Author(s):

Reika YOSHITSUGU ◽

Keidai KIKUCHI ◽

Hitoshi IWAYA ◽

Nobuyuki FUJII ◽

Shota HORI ◽

...

Keyword(s):

Bile Acid ◽

Glucose Intolerance ◽

High Fat Diet ◽

Acid Metabolism ◽

Bile Acid Metabolism ◽

High Fat

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Effectiveness of Bioactive Food Components in Experimental Colon Carcinogenesis

Acta Veterinaria Brno ◽

10.2754/avb200978040661 ◽

2009 ◽

Vol 78 (4) ◽

pp. 661-666 ◽

Cited By ~ 3

Author(s):

Emília Hijová ◽

Anna Chmelárová ◽

Alojz Bomba

Keyword(s):

Bile Acid ◽

High Fat Diet ◽

Colon Carcinogenesis ◽

Control Group ◽

Serum Bile Acid ◽

Protective Effects ◽

High Fat ◽

Bile Acid Concentration ◽

Food Components ◽

Bioactive Food Components

The aim of the present study was the evaluation of possible protective effects of selected bioactive food components in experimental N,N-dimethylhydrazine (DMH)-induced colon carcinogenesis. Wistar albino rats (n = 92) were fed a high fat diet or conventional laboratory diet. Two weeks after the beginning of the trial, DMH injections were given to six groups of rats at the dose of 20 mg/kg b.w. twice weekly. The activity of bacterial enzymes in faeces and serum bile acid concentrations were determined. High fat diet, DMH injections, and their combination significantly increased the activies of β-galactosidase, β-glucuronidase, and α-glucosidase (p < 0.001) compared to the control group of rats. Treatment with the prebiotic inulin, Hyppocastani extractum siccum and Lini oleum virginale significantly decreased the activity of β-galactosidase, β-glucuronidase, and α-glucosidase (p < 0.001), as well as the bile acid concentration compared to the group at the highest risk. The protective effects of selected bioactive food components in experimentally induced colon carcinogenesis allow for their possible use in cancer prevention or treatment.

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Metabolomic signatures for liver tissue and cecum contents in high-fat diet-induced obese mice based on UHPLC-Q-TOF/MS

Nutrition & Metabolism ◽

10.1186/s12986-021-00595-8 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Hongying Cai ◽

Zhiguo Wen ◽

Kun Meng ◽

Peilong Yang

Keyword(s):

Bile Acid ◽

High Fat Diet ◽

Unsaturated Fatty Acids ◽

Strongly Correlated ◽

Obese Mice ◽

High Fat ◽

Secondary Bile Acid ◽

Nonalcoholic Fatty Liver ◽

Flight Mass Spectrometry ◽

P 16

Abstract Background The incidence of obesity is increasing worldwide, and it is a risk factor for diabetes, dyslipidemia, and nonalcoholic fatty liver disease. Our previous study had demonstrated that high-fat diet induced increased weight gain, fat weight, serum cholesterol, triglyceride, and ATL levels in liver, and influenced the diversity and composition of cecal microbiota in mice. Hence, this study aimed to investigate the roles of the gut microbially derived metabolites and liver metabolites between the obese and lean mice, focusing on their association with the progression of obesity induced by high-fat diet (HFD). Methods An obesity model in mice was established with HFD for 16 weeks. Cecal contents and liver tissues metabolomics based on ultraperformance liquid chromatography-quadrupole-time-of-flight mass spectrometry and orthogonal partial least squares discriminant analyses (OPLS-DA) was performed to identify the alterations in metabolites associated with obese mice. Results Obese and lean groups were clearly discriminated from each other on OPLS-DA score plot and major metabolites contributing to the discrimination were mainly involved in glycerophospholipid metabolism, primary bile acid biosynthesis, and biosynthesis of unsaturated fatty acids pathways. HFD-induced alterations of 19 metabolites in liver and 43 metabolites in cecum contents were identified as potential biomarkers related to obesity. Specifically, chenodeoxycholic acid, taurochenodeoxycholate, and tauroursodeoxycholic acid in liver were elevated 35.94, 24.36, and 18.71-fold, respectively. PI(P-16:0/18:1(9Z)), PG(19:0/16:0), PS(P-16:0/20:2(11Z,14Z)), PI(22:1(11Z)/12:0), and PE(21:0/0:0) in cecum were enhanced 884, 640.96, 226.63, 210.10, 45.13-fold in comparison with the lean mice. These metabolites were the most important biomarkers for discriminating between the obese and lean mice. In addition, cecum contents metabolites were strongly correlated with hepatic metabolites through gut-liver axis analysis. Conclusions HFD increased lipid profiles (i.e. glycerophospholipids, PC, PE, PI, PG, and PS) and total bile acid (primary and secondary bile acid) in liver and cecum, suggesting that they may play an important role in the progression of obesity. These metabolites can be used to better understand obesity and related disease induced by HFD. Furthermore, the level alterations of these metabolites can be used to assess the risk of obesity and the therapeutic effect of obesity management.

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Plasticity of histone modifications around Cidea and Cidec genes with secondary bile in the amelioration of developmentally-programmed hepatic steatosis

Scientific Reports ◽

10.1038/s41598-019-52943-7 ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Jeenat Ferdous Urmi ◽

Hiroaki Itoh ◽

Keiko Muramatsu-Kato ◽

Yukiko Kohmura-Kobayashi ◽

Natsuyo Hariya ◽

...

Keyword(s):

Dna Methylation ◽

Bile Acid ◽

Hepatic Steatosis ◽

Histone Modifications ◽

High Fat Diet ◽

High Fat ◽

Secondary Bile Acid ◽

Regulated Expression ◽

Hepatic Fat ◽

Insight Into

AbstractWe recently reported that a treatment with tauroursodeoxycholic acid (TUDCA), a secondary bile acid, improved developmentally-deteriorated hepatic steatosis in an undernourishment (UN, 40% caloric restriction) in utero mouse model after a postnatal high-fat diet (HFD). We performed a microarray analysis and focused on two genes (Cidea and Cidec) because they are enhancers of lipid droplet (LD) sizes in hepatocytes and showed the greatest up-regulation in expression by UN that were completely recovered by TUDCA, concomitant with parallel changes in LD sizes. TUDCA remodeled developmentally-induced histone modifications (dimethylation of H3K4, H3K27, or H3K36), but not DNA methylation, around the Cidea and Cidec genes in UN pups only. Changes in these histone modifications may contribute to the markedly down-regulated expression of Cidea and Cidec genes in UN pups, which was observed in the alleviation of hepatic fat deposition, even under HFD. These results provide an insight into the future of precision medicine for developmentally-programmed hepatic steatosis by targeting histone modifications.

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