scholarly journals Conceptualizing the Vertebrate Sterolbiome

2020 ◽  
Vol 86 (16) ◽  
Author(s):  
Jason M. Ridlon
Keyword(s):  
Bile Acid ◽  
Molecular Biology ◽  
Bile Acids ◽  
Current Knowledge ◽  
Tissue Specific ◽  
Genes Encoding ◽  
Microbial Genes ◽  
Host Synthesis

ABSTRACT Vertebrates synthesize a diverse set of steroids and bile acids that undergo bacterial biotransformations. The endocrine literature has principally focused on the biochemistry and molecular biology of host synthesis and tissue-specific metabolism of steroids. Host-associated microbiota possess a coevolved set of steroid and bile acid modifying enzymes that match the majority of host peripheral biotransformations in addition to unique capabilities. The set of host-associated microbial genes encoding enzymes involved in steroid transformations is known as the sterolbiome. This review focuses on the current knowledge of the sterolbiome as well as its importance in medicine and agriculture.

scholarly journals Pathways and Inborn Errors of Bile Acid Synthesis

Acta Medica ◽  
2019 ◽  
Vol 50 (4) ◽  
pp. 48-56
Author(s):  
Ufuk Bozkurt Obuz ◽  
Incilay Lay
Keyword(s):  
Bile Acid ◽  
Early Diagnosis ◽  
Bile Acids ◽  
Biosynthetic Pathway ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Clinical Findings ◽  
Inborn Errors ◽  
Genes Encoding ◽  
Intracellular Compartments

Bile acids are synthesized from cholesterol through 17 different enzymes located in different intracellular compartments of hepatocytes. Defects have been identified in the genes encoding the enzymes involved in the bile acid synthesis pathways and nine different diseases have been identified so far. In this review, four different biosynthetic pathway of bile acids together with disorders of bile acid synthesis is described. In inborn errors of bile acid synthesis clinical findings can range from liver failure to cirrhosis in infancy or progressive neuropathy in adolescence / adulthood. Laboratory analysis of urine profiling of bile acids is important in early diagnosis and early treatment.

The nuclear receptor for bile acids, FXR, transactivates human organic solute transporter-α and -β genes

2006 ◽  
Vol 290 (3) ◽  
pp. G476-G485 ◽  
Author(s):  
Jean-François Landrier ◽  
Jyrki J. Eloranta ◽  
Stephan R. Vavricka ◽  
Gerd A. Kullak-Ublick
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Cultured Cells ◽  
Farnesoid X Receptor ◽  
Mrna Levels ◽  
Small Interfering Rnas ◽  
Organic Solute Transporter ◽  
Genes Encoding ◽  
Organic Solute ◽  
Solute Transporter

Bile acids are synthesized from cholesterol in the liver and are excreted into bile via the hepatocyte canalicular bile salt export pump. After their passage into the intestine, bile acids are reabsorbed in the ileum by sodium-dependent uptake across the apical membrane of enterocytes. At the basolateral domain of ileal enterocytes, bile acids are extruded into portal blood by the heterodimeric organic solute transporter OSTα/OSTβ. Although the transport function of OSTα/OSTβ has been characterized, little is known about the regulation of its expression. We show here that human OSTα/OSTβ expression is induced by bile acids through ligand-dependent transactivation of both OST genes by the nuclear bile acid receptor/farnesoid X receptor (FXR). FXR agonists induced endogenous mRNA levels of OSTα and OSTβ in cultured cells, an effect that was not discernible upon inhibition of FXR expression by small interfering RNAs. Furthermore, OST mRNAs were induced in human ileal biopsies exposed to the bile acid chenodeoxycholic acid. Reporter constructs containing OSTα or OSTβ promoters were transactivated by FXR in the presence of its ligand. Two functional FXR binding motifs were identified in the OSTα gene and one in the OSTβ gene. Targeted mutation of these elements led to reduced inducibility of both OST promoters by FXR. In conclusion, the genes encoding the human OSTα/OSTβ complex are induced by bile acids and FXR. By coordinated control of OSTα/OSTβ expression, bile acids may adjust the rate of their own efflux from enterocytes in response to changes in intracellular bile acid levels.

scholarly journals Metabolic consequences of ileal interruption of the enterohepatic circulation of bile acids

2020 ◽  
Vol 319 (5) ◽  
pp. G619-G625
Author(s):  
Ivo P. van de Peppel ◽  
Henkjan J. Verkade ◽  
Johan W. Jonker
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Enterohepatic Circulation ◽  
Current Knowledge ◽  
Whole Body ◽  
Novel Studies ◽  
Sodium Dependent ◽  
Bile Acid Transporter ◽  
Bile Acid Secretion ◽  
Different Levels

The enterohepatic circulation of bile acids comprises a tightly regulated process of hepatic bile acid secretion, intestinal reabsorption and transport back to the liver. Disruption of this process has significant consequences for gastrointestinal, liver and whole body homeostasis and therefore offers opportunities for therapeutic intervention. In this review we discuss the effects of (pharmacological) interruption of the enterohepatic circulation at different levels. Recently, several studies have been published on ileal interruption of the enterohepatic circulation of bile acids, targeting the apical-sodium dependent bile acid transporter (ASBT, SLC10A2), as therapy for various diseases. However, ambiguous results have been reported and in-depth mechanistic insights are lacking. Here we discuss these novel studies and review the current knowledge on the consequences of ASBT inhibition and its potential effects on physiology and metabolism.

scholarly journals Antagonism of the Actions of Peroxisome Proliferator-activated Receptor-α by Bile Acids

2001 ◽  
Vol 276 (50) ◽  
pp. 47154-47162 ◽  
Author(s):  
Christopher J. Sinal ◽  
Michung Yoon ◽  
Frank J. Gonzalez
Keyword(s):  
Fatty Acid ◽  
Bile Acid ◽  
Bile Acids ◽  
The Body ◽  
Peroxisome Proliferator ◽  
Acid Biosynthesis ◽  
Peroxisome Proliferator Activated Receptor ◽  
Bile Acid Biosynthesis ◽  
Genes Encoding ◽  
The Impact

The peroxisome proliferator-activated receptor-α (PPARα) is a ligand-activated transcription factor that regulates the expression of a number of genes critical for fatty acid β-oxidation. Because a number of substrates and intermediates of this metabolic pathway serve as ligand activators of this receptor, homeostatic control of fatty acid metabolism is achieved. Evidence also exists for PPARα-dependent regulation of genes encoding critical enzymes of bile acid biosynthesis. To determine whether the primary products of bile acid biosynthesis, cholic acid and chenodeoxycholic acid, were capable of modulating PPARα function, a variety ofin vivoandin vitroapproaches were utilized. Feeding a bile acid-enriched diet significantly reduced the degree of hepatomegaly and induction of target genes encoding enzymes of fatty acid β-oxidation caused by treatment with the potent PPARα ligand Wyeth-14,643. Convergent data from mechanistic studies indicate that bile acids interfere with transactivation by PPARα at least in part by impairing the recruitment of transcriptional coactivators. The results of this study provide the first evidence in favor of the existence of compounds, normally found within the body, that are capable of antagonizing the physiological actions of PPARα. The impact of PPARα antagonism by endogenous bile acids is likely to be limited under normal conditions and to have only minimal effects on bile acid homeostasis. However, during certain pathophysiological states where intracellular bile acid concentrations are elevated, meaningful effects on PPARα-dependent target gene regulation are possible.

Dominant Bacterial Phyla from the Human Gut Show Widespread Ability To Transform and Conjugate Bile Acids

mSystems ◽  
2021 ◽  
Vol 6 (4) ◽  
Author(s):  
L. N. Lucas ◽  
K. Barrett ◽  
R. L. Kerby ◽  
Q. Zhang ◽  
L. E. Cattaneo ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Current Knowledge ◽  
Human Gut ◽  
Bacterial Phyla ◽  
Microbial Species ◽  
Number Of Species ◽  
Biochemical Studies

Our current knowledge regarding microbial bile acid transformations comes primarily from biochemical studies on a relatively small number of species or from bioinformatic predictions that rely on homology to known bile acid-transforming enzyme sequences. Therefore, much remains to be learned regarding the variety of bile acid transformations and their representation across gut microbial species.

scholarly journals Defective canalicular transport and toxicity of dietary ursodeoxycholic acid in the abcb11−/− mouse: transport and gene expression studies

2013 ◽  
Vol 305 (4) ◽  
pp. G286-G294 ◽  
Author(s):  
Renxue Wang ◽  
Lin Liu ◽  
Jonathan A. Sheps ◽  
Dana Forrest ◽  
Alan F. Hofmann ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bile Acid ◽  
Ursodeoxycholic Acid ◽  
Bile Acids ◽  
Bile Flow ◽  
Biliary Cirrhosis ◽  
Beneficial Effects ◽  
Elevated Liver Enzymes ◽  
Genes Encoding ◽  
End Stage

The bile salt export pump (BSEP), encoded by the abcb11 gene, is the major canalicular transporter of bile acids from the hepatocyte. BSEP malfunction in humans causes bile acid retention and progressive liver injury, ultimately leading to end-stage liver failure. The natural, hydrophilic, bile acid ursodeoxycholic acid (UDCA) is efficacious in the treatment of cholestatic conditions, such as primary biliary cirrhosis and cholestasis of pregnancy. The beneficial effects of UDCA include promoting bile flow, reducing hepatic inflammation, preventing apoptosis, and maintaining mitochondrial integrity in hepatocytes. However, the role of BSEP in mediating UDCA efficacy is not known. Here, we used abcb11 knockout mice ( abcb11 −/−) to test the effects of acute and chronic UDCA administration on biliary secretion, bile acid composition, liver histology, and liver gene expression. Acutely infused UDCA, or its taurine conjugate (TUDC), was taken up by the liver but retained, with negligible biliary output, in abcb11−/− mice. Feeding UDCA to abcb11−/− mice led to weight loss, retention of bile acids, elevated liver enzymes, and histological damage to the liver. Semiquantitative RT-PCR showed that genes encoding Mdr1a and Mdr1b (canalicular) as well as Mrp4 (basolateral) transporters were upregulated in abcb11−/− mice. We concluded that infusion of UDCA and TUDC failed to induce bile flow in abcb11−/− mice. UDCA fed to abcb11−/− mice caused liver damage and the appearance of biliary tetra- and penta-hydroxy bile acids. Supplementation with UDCA in the absence of Bsep caused adverse effects in abcb11−/− mice.

Pharmacological effects of secondary bile acid microparticles in diabetic murine model

2020 ◽  
Vol 16 ◽  
Author(s):  
Armin Mooranian ◽  
Nassim Zamani ◽  
Bozica Kovacevic ◽  
Corina Mihaela Ionescu ◽  
Giuseppe Luna ◽  
...  
Keyword(s):  
Bile Acid ◽  
Blood Glucose ◽  
Bile Acids ◽  
Lithocholic Acid ◽  
Diabetes Treatment ◽  
Secondary Bile Acid ◽  
Glucose Levels ◽  
Anti Inflammatory ◽  
Antidiabetic Effects

Aim: Examine bile acids effects in Type 2 diabetes. Background: In recent studies, the bile acid ursodeoxycholic acid (UDCA) has shown potent anti-inflammatory effects in obese patients while in type 2 diabetics (T2D) levels of the pro-inflammatory bile acid lithocholic acid were increased, and levels of the anti-inflammatory bile acid chenodeoxycholic acid were decreased, in plasma. Objective: Hence, this study aimed to examine applications of novel UDCA nanoparticles in diabetes. Methods: Diabetic balb/c adult mice were divided into three equal groups and gavaged daily with either empty microcapsules, free UDCA, or microencapsulated UDCA over two weeks. Their blood, tissues, urine, and faeces were collected for blood glucose, inflammation, and bile acid analyses. UDCA resulted in modulatory effects on bile acids profile without antidiabetic effects suggesting that bile acid modulation was not directly linked to diabetes treatment. Results: UDCA resulted in modulatory effects on bile acids profile without antidiabetic effects suggesting that bile acid modulation was not directly linked to diabetes treatment. Conclusion: Bile acids modulated the bile profile without affecting blood glucose levels.

scholarly journals Manipulating the Microbiome: An Alternative Treatment for Bile Acid Diarrhoea

2021 ◽  
Vol 12 (2) ◽  
pp. 335-353
Author(s):  
Evette B. M. Hillman ◽  
Sjoerd Rijpkema ◽  
Danielle Carson ◽  
Ramesh P. Arasaradnam ◽  
Elizabeth M. H. Wellington ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Gastrointestinal Disease ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Bile Acid Metabolism ◽  
The United Kingdom ◽  
The 1960S ◽  
Irritable Bowel ◽  
The Uk

Bile acid diarrhoea (BAD) is a widespread gastrointestinal disease that is often misdiagnosed as irritable bowel syndrome and is estimated to affect 1% of the United Kingdom (UK) population alone. BAD is associated with excessive bile acid synthesis secondary to a gastrointestinal or idiopathic disorder (also known as primary BAD). Current licensed treatment in the UK has undesirable effects and has been the same since BAD was first discovered in the 1960s. Bacteria are essential in transforming primary bile acids into secondary bile acids. The profile of an individual’s bile acid pool is central in bile acid homeostasis as bile acids regulate their own synthesis. Therefore, microbiome dysbiosis incurred through changes in diet, stress levels and the introduction of antibiotics may contribute to or be the cause of primary BAD. This literature review focuses on primary BAD, providing an overview of bile acid metabolism, the role of the human gut microbiome in BAD and the potential options for therapeutic intervention in primary BAD through manipulation of the microbiome.

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