The Importance of Bile Acids in Human Diseases

Fromm, Hans; Hofmann, Andreas

doi:10.1007/978-3-642-66015-3_5

Cited by 6 publications

(3 citation statements)

References 178 publications

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“…Interestingly, reports that the microbiome dictates the BA pool (2,20,31) and that bacterial dysbiosis is seen in intestinal diseases such as NEC (25,26) and IBD (39) may point to a mechanism by which the microbiome alters the host intestine. Indeed, in the formula-feeding-hypoxia neonatal rat model of NEC, DCA levels are elevated (vs. dam-fed littermates) in the lumen of the terminal ileum by 24 -48 h (26, 27), while histological damage is not seen until 72 h. DCA levels are much lower in human infants that are breast-fed (29), and breast feeding has long been considered protective from NEC (45).…”

Section: Discussionmentioning

confidence: 99%

Bile acids regulate intestinal cell proliferation by modulating EGFR and FXR signaling

Dossa

Escobar

Golden

et al. 2016

American Journal of Physiology-Gastrointestinal and Liver Physi

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Bile acids (BAs) are synthesized in the liver and secreted into the intestine. In the lumen, enteric bacteria metabolize BAs from conjugated, primary forms into more toxic unconjugated, secondary metabolites. Secondary BAs can be injurious to the intestine and may contribute to disease. The epidermal growth factor receptor (EGFR) and the nuclear farnesoid X receptor (FXR) are known to interact with BAs. In this study we examined the effects of BAs on intestinal epithelial cell proliferation and investigated the possible roles for EGFR and FXR in these effects. We report that taurine-conjugated cholic acid (TCA) induced proliferation, while its unconjugated secondary counterpart deoxycholic acid (DCA) inhibited proliferation. TCA stimulated phosphorylation of Src, EGFR, and ERK 1/2. Pharmacological blockade of any of these pathways or genetic ablation of EGFR abrogated TCA-stimulated proliferation. Interestingly, Src or EGFR inhibitors eliminated TCA-induced phosphorylation of both molecules, suggesting that their activation is interdependent. In contrast to TCA, DCA exposure diminished EGFR phosphorylation, and pharmacological or siRNA blockade of FXR abolished DCA-induced inhibition of proliferation. Taken together, these results suggest that TCA induces intestinal cell proliferation via Src, EGFR, and ERK activation. In contrast, DCA inhibits proliferation via an FXR-dependent mechanism that may include downstream inactivation of the EGFR/Src/ERK pathway. Since elevated secondary BA levels are the result of specific bacterial modification, this may provide a mechanism through which an altered microbiota contributes to normal or abnormal intestinal epithelial cell proliferation.

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Section: Discussionmentioning

confidence: 99%

Bile acids regulate intestinal cell proliferation by modulating EGFR and FXR signaling

Dossa

Escobar

Golden

et al. 2016

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Bile acids are steroidal tensoactives biosynthesized in the liver and which form mixed micelles with cholesterol and other lipids to enable fat digestion. For this purpose, they travel to the intestine, separate from the ingested lipids, and return to the liver for reuse in a movement known as enterohepatic circulation. , Among bile acids (Figure ), the most abundant are cholic, deoxycholic, and chenodeoxycholic, either alone or conjugated to glycine or taurine to increase aqueous solubility at physiological pH.…”

Section: Introductionmentioning

confidence: 99%

Complexes between Fluorescent Cholic Acid Derivatives and Human Serum Albumin. A Photophysical Approach To Investigate the Binding Behavior

2010

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Interaction between bile acids and plasma proteins has attracted considerable attention over past decades. In fact, binding of bile acids to human serum albumin (HSA) determines their level in plasma, a value that can be used as a test for liver function. However, very little is known about the role that bile acids-HSA complexes play in hepatic uptake. In the present paper, we report on the utility of the singlet excited state properties of 4-nitrobenzo-2-oxa-1,3-diazole (NBD) fluorescent derivatives of cholic acid (ChA); namely, 3alpha-NBD-ChA, 3beta-NBD-ChA, 3beta-NBD-ChTau, 7alpha-NBD-ChA, and 7beta-NBD-ChA to clarify key aspects of bile acids-HSA interactions that remain poorly understood. On the basis of either absorption or emission measurements, formation of NBD-ChA@HSA complexes with 1:1 stoichiometry has been proven. Enhancement of the fluorescence emission upon addition of HSA has been used for determination of the binding constants, which are in the range of 10(4) M(-1). Energy transfer from tryptophan to NBD-ChA occurs by a FRET mechanism; the donor-acceptor distances have been determined according to Forster's theory. The estimated values (27-30 A) are compatible with both site I and site II occupancy and do not provide sufficient information for a safe assignment; however, fluorescence titration using warfarin (site I probe) and ibuprofen (site II probe) for displacement clearly indicates that the employed cholic acid derivatives bind to HSA at site I.

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“…In the terminal ileum, bile acids are reabsorbed by efficient active transport leading to a daily fecal loss of only 1-2 mmol [2], Loss of ileal absorptive func tion is followed by passage of increased amounts of bile acids into the large bowel leading to watery diarrhea [3,4], In the differential diagnosis of diarrheal disorders, increased fecal bile acid loss has been measured using 24-,4C-taurocholate as a marker [4,5] or by chemical analysis of fecal bile acids [6,7], However, the use of 14C-labeled tracers and the need of stool col lection and fecal analysis are not popular in clinical routine.…”

Section: Introductionmentioning

confidence: 99%

Comparison of <sup>75</sup>SeHCAT Retention Half-Life and Fecal Content of Individual Bile Acids in Patients with Chronic Diarrheal Disorders

Scheurlen¹,

Kruis²,

Büll³

et al. 1986

Digestion

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Measurement of the retention of 23–⁷⁵Se-25-homotaurocholic acid (SeHCAT) has been suggested as a new test for ileal function. We investigated 31 patients with chronic diarrhea, 10 with ileal Crohn’s disease and 21 with diarrhea but without ileal disease. The whole-body retention half-life of 1 μCi SeHCAT was determined and compared to the fecal content of total and individual bile acids. Patients with ileal disease had increased primary fecal bile acids (chenodeoxycholic acid: mean 6.95 mg/g dry weight, range 3.15–10.6 mg/g; cholic acid: mean 18.15 mg/g, range 10.3–33.9 mg/g) and a short SeHCAT retention (mean 11.9 h, range 2–24 h), whereas patients with intact ileum had normal fecal bile acids and a SeHCAT retention of 85.9 h (range 28–216 h). SeHCAT retention half-life differentiated well between patients with ileal disease and patients with normal ileum, thus indicating the SeHCAT test as a valid investigation method for detection of primary bile acid malabsorption in patients with chronic diarrhea and ileal dysfunction.

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The Importance of Bile Acids in Human Diseases

Cited by 6 publications

References 178 publications

Bile acids regulate intestinal cell proliferation by modulating EGFR and FXR signaling

Bile acids regulate intestinal cell proliferation by modulating EGFR and FXR signaling

Complexes between Fluorescent Cholic Acid Derivatives and Human Serum Albumin. A Photophysical Approach To Investigate the Binding Behavior

Comparison of <sup>75</sup>SeHCAT Retention Half-Life and Fecal Content of Individual Bile Acids in Patients with Chronic Diarrheal Disorders

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