Compensatory Transition of Bile Acid Metabolism from Fecal Disposition of Secondary Bile Acids to Urinary Excretion of Primary Bile Acids Underlies Rifampicin-Induced Cholestasis in Beagle Dogs

2021 ◽  
Author(s):  
LanLan Gui ◽  
QingLiang Wu ◽  
YiTing Hu ◽  
WuShuang Zeng ◽  
XianWen Tan ◽  
...  
Keyword(s):  
Bile Acid ◽  
Urinary Excretion ◽  
Bile Acids ◽  
Acid Metabolism ◽  
Bile Acid Metabolism ◽  
Beagle Dogs ◽  
Secondary Bile Acids

scholarly journals The influence of probiotics on individual fecal secondary bile acid levels: a two-case study of schizophrenic patients receiving an atypical antipsychotic drug

2017 ◽  
Vol 7 (11) ◽  
pp. 849
Author(s):  
Yosuke Saito ◽  
Hiroyuki Nishimiya ◽  
Yasue Kondo ◽  
Toyoaki Sagae
Keyword(s):  
Bile Acid ◽  
Bile Salt ◽  
Bile Acids ◽  
Acid Metabolism ◽  
Bile Acid Metabolism ◽  
Bile Salt Hydrolase ◽  
Atypical Antipsychotic Drug ◽  
Secondary Bile Acid ◽  
Secondary Bile Acids ◽  
Bsh Activity

Background: Probiotics is used as a promising approach in the prevention and treatment of hypercholesterolemia. Modification of bile acid metabolism through the deconjugation of bile salts by microbial bile salt hydrolase (BSH) is considered to be the core mechanism of the hypocholesterolemic effects of probiotics. Nevertheless, BSH activity is reported to be detrimental to the human host due to the generation of toxic secondary bile acids. Thus, the influence of probiotic intake on bile acid metabolism needs to be elucidated. We analyzed the bile acid levels and microbiota in human fecal samples after probiotic supplementation to assess the influence of probiotic intake on fecal bile acid levels. Two patients hospitalized for schizophrenia and dyslipidemia, receiving an atypical antipsychotic drug, were enrolled in this study (Subjects A and B). Both subjects received Lactobacillus rhamnosus GG (LGG) for 4 weeks, and no probiotics for the following 4 weeks. Fecal samples were collected at baseline and after 4 and 8 weeks.Results: Conjugated bile acids may be modified by indigenous intestinal bacteria into unconjugated bile acids and secondary bile acids through deconjugation reactions by BSH activity and the subsequent 7a-dehydroxylation pathway, respectively. In the fecal microbiota from Subject A, the relative abundance of Bifidobacterium increased after LGG supplementation (30%–49%). Most Bifidobacterium and Lactobacillus strains that colonize mammalian intestines may report BSH activity, and in general bifidobacteria reveals a higher BSH activity than lactobacilli. The fecal unconjugated bile acid and secondary bile acid levels in Subject A increased after the LGG supplementation (0.36–1.79 and 1.82–16.19 mmol/g respectively). Although the LGG supplementation appears to promote bile acid deconjugation, most of the unconjugated bile acids in Subject A appear to have been modified into secondary bile acids. Alternatively, in Subject B there were no significant changes throughout the study.Conclusion: We observed a significant increase in the fecal secondary bile acid levels after probiotic administration in one of our cases. Further studies are needed to elucidate the factors affecting 7a-dehydroxylation of bile acids to confirm the safety of using probiotics.Keywords: bile salt hydrolase; BSH; dihydroxylation; Bifidobacterium

scholarly journals Clostridium scindensATCC 35704: Integration of Nutritional Requirements, the Complete Genome Sequence, and Global Transcriptional Responses to Bile Acids

2019 ◽  
Vol 85 (7) ◽  
Author(s):  
Saravanan Devendran ◽  
Rachana Shrestha ◽  
João M. P. Alves ◽  
Patricia G. Wolf ◽  
Lindsey Ly ◽  
...  
Keyword(s):  
Bile Acid ◽  
Amino Acid ◽  
Bile Acids ◽  
Cholic Acid ◽  
Acid Metabolism ◽  
Deoxycholic Acid ◽  
Nutritional Requirements ◽  
Bile Acid Metabolism ◽  
Content Type ◽  
Secondary Bile Acids

ABSTRACTIn the human gut,Clostridium scindensATCC 35704 is a predominant bacterium and one of the major bile acid 7α-dehydroxylating anaerobes. While this organism is well-studied relative to bile acid metabolism, little is known about the basic nutrition and physiology ofC. scindensATCC 35704. To determine the amino acid and vitamin requirements ofC. scindens, the leave-one-out (one amino acid group or vitamin) technique was used to eliminate the nonessential amino acids and vitamins. With this approach, the amino acid tryptophan and three vitamins (riboflavin, pantothenate, and pyridoxal) were found to be required for the growth ofC. scindens. In the newly developed defined medium,C. scindensfermented glucose mainly to ethanol, acetate, formate, and H2.The genome ofC. scindensATCC 35704 was completed through PacBio sequencing. Pathway analysis of the genome sequence coupled with transcriptome sequencing (RNA-Seq) under defined culture conditions revealed consistency with the growth requirements and end products of glucose metabolism. Induction with bile acids revealed complex and differential responses to cholic acid and deoxycholic acid, including the expression of potentially novel bile acid-inducible genes involved in cholic acid metabolism. Responses to toxic deoxycholic acid included expression of genes predicted to be involved in DNA repair, oxidative stress, cell wall maintenance/metabolism, chaperone synthesis, and downregulation of one-third of the genome. These analyses provide valuable insight into the overall biology ofC. scindenswhich may be important in treatment of disease associated with increased colonic secondary bile acids.IMPORTANCEC. scindensis one of a few identified gut bacterial species capable of converting host cholic acid into disease-associated secondary bile acids such as deoxycholic acid. The current work represents an important advance in understanding the nutritional requirements and response to bile acids of the medically important human gut bacterium,C. scindensATCC 35704. A defined medium has been developed which will further the understanding of bile acid metabolism in the context of growth substrates, cofactors, and other metabolites in the vertebrate gut. Analysis of the complete genome supports the nutritional requirements reported here. Genome-wide transcriptomic analysis of gene expression in the presence of cholic acid and deoxycholic acid provides a unique insight into the complex response ofC. scindensATCC 35704 to primary and secondary bile acids. Also revealed are genes with the potential to function in bile acid transport and metabolism.

scholarly journals Impaired absorption of cholesterol and bile acids in patients with an ileoanal anastomosis

Gut ◽  
1997 ◽  
Vol 41 (6) ◽  
pp. 771-777 ◽  
Author(s):  
K Hakala ◽  
M Vuoristo ◽  
P Luukkonen ◽  
H J Järvinen ◽  
T A Miettinen
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Acid Metabolism ◽  
Saturation Index ◽  
Low Density Lipoprotein ◽  
Ileoanal Anastomosis ◽  
Density Lipoprotein ◽  
Cholesterol Absorption ◽  
Bile Acid Metabolism ◽  
Secondary Bile Acids

Background—No data exist on cholesterol absorption in patients with an ileoanal anastomosis (IAA).Aims—To study cholesterol absorption and its effects on cholesterol and bile acid metabolism in patients with an IAA.Patients and methods—Cholesterol absorption, and serum, biliary, and faecal lipids were studied in 24 patients with an IAA and 20 controls.Results—Fractional cholesterol absorption was significantly lower in the patients (36% versus 47% in controls). Surprisingly, the calculated intestinal influx of endogenous cholesterol was reduced so that the absolute absorption of cholesterol was decreased; elimination of cholesterol as faecal neutral steroids remained normal. Thus, the slightly increased cholesterol synthesis was mainly due to increased faecal bile acid excretion, which, in turn, was associated with reduced absorption and biliary secretion of bile acids. Serum total and low density lipoprotein (LDL) cholesterol and LDL triglycerides were lower in the patients. Molar percentage and saturation index of biliary cholesterol were slightly higher in patients with an IAA. Proportions of secondary bile acids in bile and faeces were diminished, and faecal unidentified bile acids were higher in patients.Conclusions—Cholesterol absorption is significantly impaired in patients with an IAA, and is closely related to changes in serum and biliary lipids observed in these patients.

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 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.

Sign in / Sign up

Export Citation Format

Share Document