scholarly journals Comprehensive Characterization of Bile Acids in Human Biological Samples and Effect of 4-Week Strawberry Intake on Bile Acid Composition in Human Plasma

Metabolites ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 99
Author(s):  
Anqi Zhao ◽  
Liyun Zhang ◽  
Xuhuiqun Zhang ◽  
Indika Edirisinghe ◽  
Britt M. Burton-Freeman ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Human Plasma ◽  
Biological Samples ◽  
Acid Metabolism ◽  
Plasma Concentrations ◽  
Urine Samples ◽  
Bile Acid Metabolism ◽  
Comprehensive Characterization

Primary bile acids (BAs) and their gut microbial metabolites have a role in regulating human health. Comprehensive characterization of BAs species in human biological samples will aid in understanding the interaction between diet, gut microbiota, and bile acid metabolism. Therefore, we developed a qualitative method using ultra-high performance liquid chromatography (UHPLC) coupled with a quadrupole time-of-flight (Q-TOF) to identify BAs in human plasma, feces, and urine samples. A quantitative method was developed using UHPLC coupled with triple quadrupole (QQQ) and applied to a previous clinical trial conducted by our group to understand the bile acid metabolism in overweight/obese middle-aged adults (n = 34) after four weeks strawberry vs. control intervention. The qualitative study tentatively identified a total of 81 BAs in human biological samples. Several BA glucuronide-conjugates were characterized for the first time in human plasma and/or urine samples. The four-week strawberry intervention significantly reduced plasma concentrations of individual secondary BAs, deoxycholic acid, lithocholic acid and their glycine conjugates, as well as glycoursodeoxycholic acid compared to control (p < 0.05); total glucuronide-, total oxidized-, total dehydroxyl-, total secondary, and total plasma BAs were also lowered compared to control (p < 0.05). The reduced secondary BAs concentrations suggest that regular strawberry intake modulates the microbial metabolism of BAs.

Abstract 49: The Transcriptional Repressor MafG Regulates Cholesterol Catabolism

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Thomas Q de Aguiar Vallim ◽  
Elizabeth J Tarling ◽  
Hannah Ahn ◽  
Lee R Hagey ◽  
Casey E Romanoski ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Acid Metabolism ◽  
Metabolic Diseases ◽  
Cholesterol Metabolism ◽  
Transcriptional Repressor ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Bile Acid Metabolism ◽  
Biliary Bile Acid

Elevated circulating cholesterol levels is a major risk factor for cardiovascular diseases (CVD), and therefore understanding pathways that affect cholesterol metabolism are important for potential treatment of CVD. The major route for cholesterol excretion is through its catabolism to bile acids. Specific bile acids are also potent signaling molecules that modulate metabolic pathways affecting lipid, glucose and bile acid homeostasis. Bile acids are synthesized from cholesterol in the liver, and the key enzymes involved in bile acid synthesis ( Cyp7a1 , Cyp8b1 ) are regulated transcriptionally by the nuclear receptor FXR. We have identified an FXR-regulated pathway upstream of a transcriptional repressor that controls multiple bile acid metabolism genes. We identify MafG as an FXR target gene and show that hepatic MAFG overexpression represses genes of the bile acid synthetic pathway, and modifies the biliary bile acid composition. In contrast, MafG loss-of-function studies cause de-repression of the bile acid genes with concordant changes in biliary bile acid levels. Finally, we identify functional MafG response elements in bile acid metabolism genes using ChIP-Seq analysis. Our studies identify a molecular mechanism for the complex feedback regulation of bile acid synthesis controlled by FXR. The identification of this pathway will likely have important implications in metabolic diseases.

scholarly journals Identification of bile acids in the serum and urine in cholestasis. Evidence for 6α-hydroxylation of bile acids in man

1976 ◽  
Vol 154 (2) ◽  
pp. 507-516 ◽  
Author(s):  
J A. Summerfield ◽  
B H. Billing ◽  
C H. L. Shackleton
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Acid Metabolism ◽  
Gas Chromatography Mass Spectrometry ◽  
Acid Mixture ◽  
Bile Acid Metabolism ◽  
Hyodeoxycholic Acid ◽  
Normal Man ◽  
Hyocholic Acid ◽  
Sulphate Conjugate

In this qualitative study of the pattern of bile acid excretion in cholestasis, methods are described for the isolation of bile acids from large volumes of urine and plasma. The bile acids were subjected to a group separation and identified by combined gas chromatography-mass spectrometry. The techniques were developed to allow identification of the minor components of the bile acid mixture. Four bile acids that have not previously been described in human urine and plasma were detected, namely 3β, 7α-dihydroxy-5β-cholan-24-oic acid, 3α, 6α-dihydroxy-5β-cholan-24-oic acid (hyodeoxycholic acid), 3α, 6α, 7α-trihydroxy-5β-cholan-24-oic acid (hyocholic acid) and 3α, 7β, 12α-trihydroxy-5β-cholan-24-oic acid. In addition three C27 steroids were found; 26-hydroxycholesterol and a trihydroxy cholestane, probably 5 β-cholestane-3α, 7α, 26-triol were found in the sulphate fraction of plasma and urine. In the plasma sample, a sulphate conjugate of 24-hydroxycholesterol was found. The presence of these compounds probably reflects the existence of further pathways for bile acid metabolism. It is not yet known whether this is a consequence of the cholestasis or whether they are also present in normal man, at much lower concentrations.

scholarly journals Polyphenol Consumption on Human Bile Acids Metabolism: Preliminary Data of Bile Acid Profiles in Human Biological Samples (P06-131-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Anqi Zhao ◽  
Xuhuiqun Zhang ◽  
Amandeep Sandhu ◽  
Indika Edirisinghe ◽  
Barbara Shukitt-Hale ◽  
...  
Keyword(s):  
Bile Acid ◽  
Qualitative Analysis ◽  
Bile Acids ◽  
Biological Samples ◽  
Urine Samples ◽  
Fragmentation Pattern ◽  
Plasma Samples ◽  
Potential Health ◽  
Human Bile ◽  
Freeze Dried

Abstract Objectives Bile acids (BAs) play a critical role in regulating human health through the activation of BAs receptor farnesoid X receptor (FXR) and membrane G protein coupled bile acid receptor-1 (TGR5). We aimed to develop methods to characterize BAs and their metabolites in human biological samples and characterize changes in BAs profile after chronic polyphenol consumption to help guide investigations on the potential health effects of polyphenols via BAs metabolism. Methods Plasma, fecal and urine samples from two human studies that included berry intake were used for developing qualitative analysis of BAs using ultra high-performance liquid chromatography (UHPLC) coupled with electrospray ionization quadrupole time of flight (QTOF). The compounds were identified based on the exact mass, fragmentation pattern, available reference standards and database search. To investigate the effect of chronic polyphenol consumption on BAs composition, pooled plasma samples (fasting and postprandial 2 h, n = 6) from a chronic (45 and 90 days) strawberry supplementation study (24 g freeze dried/day) with an older population were analyzed. Results Among 106 BAs and their metabolites which were tentatively identified in the samples used for method development, 70, 55, and 47 BAs species were characterized in plasma, feces and urine samples, respectively. The qualitative analysis of BAs in plasma samples from subjects following the strawberry consumption protocol detected 8 primary and 31 secondary BAs. After 90-days strawberry supplementation, two secondary BAs–glycolithocholic acid and 9(11), (5β)-cholenic acid-3α, 12α-diol were decreased to undetectable levels in the pooled fasting sample and the FRX/TGR5 agonists, including chenodeoxycholic acid, deoxycholic acid, cholic acid, glycodeoxycholic acid and taurocholic acid, showed increasing peak areas at 2 h postprandial compared to fasting. Conclusions The changes in BAs profiles in fasting and postprandial plasma samples after chronic strawberry feeding suggest that strawberry polyphenols may alter BAs metabolism and the FXR/TGR5 signaling. Funding Sources This work was funded by the California Strawberry Commission, USDA Intramural Funds and various donor funds to the Center for Nutrition Research, IIT.

scholarly journals Aryl Hydrocarbon Receptor (AhR) Activation by 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) Dose-Dependently Shifts the Gut Microbiome Consistent with the Progression of Non-Alcoholic Fatty Liver Disease

2021 ◽  
Vol 22 (22) ◽  
pp. 12431
Author(s):  
Russell R. Fling ◽  
Timothy R. Zacharewski
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Fatty Liver ◽  
Bile Acids ◽  
Fatty Liver Disease ◽  
Acid Metabolism ◽  
Bile Acid Metabolism ◽  
Alcoholic Fatty Liver ◽  
Dose Dependent ◽  
Alcoholic Fatty Liver Disease

Gut dysbiosis with disrupted enterohepatic bile acid metabolism is commonly associated with non-alcoholic fatty liver disease (NAFLD) and recapitulated in a NAFLD-phenotype elicited by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice. TCDD induces hepatic fat accumulation and increases levels of secondary bile acids, including taurolithocholic acid and deoxycholic acid (microbial modified bile acids involved in host bile acid regulation signaling pathways). To investigate the effects of TCDD on the gut microbiota, the cecum contents of male C57BL/6 mice orally gavaged with sesame oil vehicle or 0.3, 3, or 30 µg/kg TCDD were examined using shotgun metagenomic sequencing. Taxonomic analysis identified dose-dependent increases in Lactobacillus species (i.e., Lactobacillus reuteri). Increased species were also associated with dose-dependent increases in bile salt hydrolase sequences, responsible for deconjugation reactions in secondary bile acid metabolism. Increased L. reuteri levels were further associated with mevalonate-dependent isopentenyl diphosphate (IPP) biosynthesis and o-succinylbenzoate synthase, a menaquinone biosynthesis associated gene. Analysis of the gut microbiomes from cirrhosis patients identified an increased abundance of genes from the mevalonate-dependent IPP biosynthesis as well as several other menaquinone biosynthesis genes, including o-succinylbenzoate synthase. These results extend the association of lactobacilli with the AhR/intestinal axis in NAFLD progression and highlight the similarities between TCDD-elicited phenotypes in mice to human NAFLD.

scholarly journals Bile acid metabolism is altered in multiple sclerosis and supplementation ameliorates neuroinflammation

2019 ◽  
Author(s):  
Pavan Bhargava ◽  
Leah Mische ◽  
Matthew D. Smith ◽  
Emily Harrington ◽  
Kathryn C Fitzgerald ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Bile Acid ◽  
Bile Acids ◽  
Acid Metabolism ◽  
White Matter Lesions ◽  
The Body ◽  
Bile Acid Metabolism ◽  
Dependent Manner ◽  
Microglial Polarization

AbstractMultiple sclerosis (MS) is an inflammatory demyelinating disorder of the CNS. Bile acids are cholesterol metabolites that can signal through receptors on cells throughout the body, including the CNS and immune system. Whether bile acid metabolism is abnormal in MS is unknown. Using global and targeted metabolomic profiling, we identified lower levels of circulating bile acid metabolites in multiple cohorts of adult and pediatric MS patients compared to controls. In white matter lesions from MS brain tissue, we noted the presence of bile acid receptors on immune and glial cells. To mechanistically examine the implications of lower levels of bile acids in MS, we studied the in vitro effects of an endogenous bile acid – tauroursodeoxycholic acid (TUDCA) on astrocyte and microglial polarization. TUDCA prevented neurotoxic (A1) polarization of astrocytes and pro-inflammatory polarization of microglia in a dose-dependent manner. TUDCA supplementation in experimental autoimmune encephalomyelitis reduced severity of disease, based on behavioral and pathological measures. We demonstrate that bile acid metabolism is altered in MS; bile acid supplementation prevents polarization of astrocytes and microglia to neurotoxic phenotypes and ameliorates neuropathology in an animal model of MS. These findings identify dysregulated bile acid metabolism as a potential therapeutic target in MS.

scholarly journals Effects of Rhein on Bile Acid Homeostasis in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Zhong Xian ◽  
Jingzhuo Tian ◽  
Lianmei Wang ◽  
Yushi Zhang ◽  
Jiayin Han ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Acid Metabolism ◽  
Farnesoid X Receptor ◽  
Bile Acid Metabolism ◽  
Edible Plant ◽  
Clinical Dose ◽  
Acid Accumulation ◽  
Liver And Kidney ◽  
Hepatic Transporters

Rhein, the active ingredient of rhubarb, a medicinal and edible plant, is widely used in clinical practice. However, the effects of repeated intake of rhein on liver function and bile acid metabolism are rarely reported. In this work, we investigated the alterations of 14 bile acids and hepatic transporters after rats were administered with rhein for 5 weeks. There was no obvious injury to the liver and kidney, and there were no significant changes in biochemical indicators. However, 1,000 mg/kg rhein increased the liver total bile acid (TBA) levels, especially taurine-conjugated bile acids (t-CBAs), inhibited the expression of farnesoid X receptor (FXR), small heterodimer partner (SHP), and bile salt export pump (BSEP) mRNA, and upregulated the expression of (cholesterol 7α-hydroxylase) CYP7A1 mRNA. Rhein close to the clinical dose (10 mg/kg and 30 mg/kg) reduced the amounts of TBAs, especially unconjugated bile acids (UCBAs), and elevated the expression of FXR and multidrug resistance-associated protein 3 (Mrp3) mRNA. These results denote that rhein is relatively safe to use at a reasonable dose and timing. 30 mg/kg rhein may promote bile acid transport and reduce bile acid accumulation by upregulating the expression of FXR mRNA and Mrp3 mRNA, potentially resulting in the decrease in serum UBCAs.

scholarly journals The Microbiome in Functional Gastrointestinal Disorders Is Characterized by Bacteria and Genes Involved in Carbohydrate and Bile Acid Metabolism (OR23-01-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Wayne Young ◽  
Caterina Carco ◽  
Jane Mullaney ◽  
Paul Maclean ◽  
Paul Cotter ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Acid Metabolism ◽  
Functional Gastrointestinal Disorders ◽  
Functional Constipation ◽  
Reference Database ◽  
Bile Acid Metabolism ◽  
Metagenomic Sequencing ◽  
Fecal Samples ◽  
Wide Range

Abstract Objectives Irritable Bowel Syndrome (IBS) is a functional gastrointestinal (GI) disorder featuring chronic or recurrent abdominal discomfort, usually with changes in GI habit. To improve our understanding of links between the microbiome and IBS, and how these links can be manipulated through diet, we undertook shotgun metagenomic sequencing of fecal samples from a case-control study. Methods Fecal samples from 172 individuals were analyzed by shotgun sequencing using the Illumina NextSeq platform. Of these, 77 were classified as controls, 16 were constipation-predominant IBS (IBS-C), 39 were diarrhea-predominant IBS (IBS-D), 29 were diagnosed with functional constipation (FC), and 11 had functional diarrhea (FD). Taxonomic classifications were determined using Metaxa2 and the SILVA 128 database. Gene functions were assigned by alignment of sequences against a protein reference database using DIAMOND. Mean relative abundance of bacterial taxa and functional genes were compared using permutation ANOVA. Ethical approval was obtained from the University of Otago Human Ethics Committee (Health) (Reference H16/094). Results Bacterial genera that discriminated case-controls (P < 0.05) from those with constipation (IBS-C + FC) and diarrhea (IBS-D + FD) included Megasphaera (increased in those with constipation), Blautia (increased in those with diarrhea), and Bilophila (increased in both constipation and diarrhea groups). Megasphaera and Blautia include bacteria that are bile-resistant and produce butyrate, possessing a wide range of Carbohydrate-Active enzymes. Bilophila are sulfite-reducing bacteria that are able to utilize bile-acids. Associated with these taxonomic differences, a wide range of genes involved in carbohydrate, energy, and amino acid metabolism differed significantly (P < 0.05), including some involved in taurine and glycine metabolism. Bile acids are conjugated with taurine or glycine in the liver, and these amino acids are removed by the action of members of the GI microbiota. Conclusions Results from our study suggest carbohydrate and bile acid metabolism by the GI microbiome may be important distinguishing characteristics in functional GI disorders. Funding Sources Funded by the New Zealand National Science Challenge High-Value Nutrition program.

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