The degenerin region of the human bile acid-sensitive ion channel (BASIC) is involved in channel inhibition by calcium and activation by bile acids

Microbial metabolism in the gut may alter human bile acid metabolism in a way that beneficially affects lipid homeostasis and therefore cardiovascular disease risk. Deconjugation of bile acids by microbes is thought to be key to this mechanism but has yet to be characterised in blood and stool while observing lipid markers. The aim of this study was to determine the effect of 3 different probiotic strains on plasma and stool bile acids in the context of lipid and glucose metabolism. In this 18-week, randomised, double-blind crossover study, healthy adults (53±8 years) with a high waist circumference underwent a 1-week pre-baseline period and were then randomised to receive 1 capsule/day of Bacillus subtilis R0179 (2.5×109 cfu/capsule; n=39), Lactobacillus plantarum HA-119 (5×109 cfu/capsule; n=38), Bifidobacterium animalis subsp. lactis B94 (5×109 cfu/capsule; n=37) or placebo for 6 weeks. Following a 3-week washout and second pre-baseline week, participants were crossed to the other intervention for 6 weeks followed by a 1-week post-intervention period. Blood and stool samples were collected at the beginning and end of each intervention to measure bile acids, serum lipid profiles, and glucose and insulin levels. Data from the placebo intervention were combined for all participants for analyses. In obese participants, the difference (final-baseline) in the sum of deconjugated plasma bile acids was greater with consumption of B. subtilis (691±378 nmol/l, P=0.01) and B. lactis (380±165 nmol/l, P=0.04) than with placebo (98±176 nmol/l, n=57). No significant differences were observed for any probiotics for stool bile acids, serum lipids, blood glucose or insulin. These data suggest that B. subtilis and B. lactis had no effect on glucose metabolism or serum cholesterol but increased deconjugated plasma bile acids in obese individuals. Additional studies should be conducted to confirm these findings and explore potential mechanisms. This trial was registered at clinicaltrials.gov as NCT01879098.

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

Current Developments in Nutrition ◽

10.1093/cdn/nzz031.p06-131-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Cited By ~ 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.

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Pharmacological and electrophysiological characterization of the human bile acid-sensitive ion channel (hBASIC)

Pflügers Archiv - European Journal of Physiology ◽

10.1007/s00424-013-1310-4 ◽

2013 ◽

Vol 466 (2) ◽

pp. 253-263 ◽

Cited By ~ 15

Author(s):

Cathérine M. T. Lefèvre ◽

Alexei Diakov ◽

Silke Haerteis ◽

Christoph Korbmacher ◽

Stefan Gründer ◽

...

Keyword(s):

Bile Acid ◽

Ion Channel ◽

Human Bile ◽

Electrophysiological Characterization

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The bile acid-sensitive ion channel (BASIC) mediates bile acid-dependent currents in bile duct epithelial cells

Pflügers Archiv - European Journal of Physiology ◽

10.1007/s00424-021-02622-2 ◽

2021 ◽

Author(s):

Shari Wiegreffe ◽

Daniel Löhrer ◽

Monika Wirtz ◽

Dominik Wiemuth

Keyword(s):

Bile Acid ◽

Ion Channel ◽

Bile Acids ◽

Epithelial Transport ◽

Ussing Chamber ◽

Cell Types ◽

Brush Cells ◽

Genetic Ablation ◽

Normal Rat ◽

Dependent Modification

AbstractThe bile acid-sensitive ion channel (BASIC) is a member of the Deg/ENaC family of ion channels that is activated by bile acids. Despite the identification of cholangiocytes in the liver and unipolar brush cells in the cerebellum as sites of expression, the physiological function of BASIC in these cell types is not yet understood. Here we used a cholangiocyte cell line, normal rat cholangiocytes (NRCs), which expresses BASIC to study the role of the channel in epithelial transport using Ussing chamber experiments. Apical application of bile acids induced robust and transient increases in transepithelial currents that were carried by Na+ and partly blocked by the BASIC inhibitor diminazene. Genetic ablation of the BASIC gene in NRC using a CRISPR-cas9 approach resulted in a decrease of the bile acid-mediated response that matched the diminazene-sensitive current in NRC WT cells, suggesting that cholangiocytes respond to bile acids with a BASIC-mediated Na+ influx. Taken together, we have identified BASIC as a component of the cholangiocyte transport machinery, which might mediate a bile acid-dependent modification of the bile and thus control bile flux and composition.

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Effect of bile and bile acids on binding of intrinsic factor to cobalamin and intrinsic factor-cobalamin complex to ileal receptor

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1983.245.1.g72 ◽

1983 ◽

Vol 245 (1) ◽

pp. G72-G77

Author(s):

B. Seetharam ◽

M. Jimenez ◽

D. H. Alpers

Keyword(s):

Bile Acid ◽

Bile Acids ◽

Intrinsic Factor ◽

Binding Ability ◽

Human Bile ◽

Receptor Molecule ◽

Protease Digestion ◽

Normal Absorption

Human bile or commercially available bile acids bind [57Co]cobalamin (Cbl) due to the presence of "R"-type binders, which are normally present in the former and present as a contaminant in the latter. The competition of these R proteins for the binding of Cbl by intrinsic factor (IF) could explain the in vivo inhibition attributed previously to the bile acids themselves. R protein seems to be involved in the inhibition of Cbl binding because protease digestion of either bile or bile acid abolishes the Cbl binding ability. Moreover, antibody to R protein abolishes the inhibition. Bile or bile acids do not have a direct effect on either purified IF or the IF-Cbl receptor molecule, even though bile acids increase the attachment of IF-[57Co]Cbl to ileal brush-border membranes. These data demonstrate two steps where components of bile could affect Cbl absorption: the binding of Cbl to IF and of IF-Cbl to its ileal receptor. It is not clear whether these in vitro phenomena are important for the normal absorption of Cbl in vivo.

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Regulation of the human bile acid UDP-glucuronosyltransferase 1A3 by the farnesoid X receptor and bile acids

Journal of Hepatology ◽

10.1016/j.jhep.2010.01.010 ◽

2010 ◽

Vol 52 (4) ◽

pp. 570-578 ◽

Cited By ~ 31

Author(s):

Thomas J. Erichsen ◽

André Aehlen ◽

Ursula Ehmer ◽

Sandra Kalthoff ◽

Michael P. Manns ◽

...

Keyword(s):

Bile Acid ◽

Bile Acids ◽

Farnesoid X Receptor ◽

Human Bile ◽

Udp Glucuronosyltransferase

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Comparison of the affinities of newly identified human bile acid binder and cationic glutathione S-transferase for bile acids.

The Journal of Lipid Research ◽

10.1016/s0022-2275(20)38812-x ◽

1988 ◽

Vol 27 (6) ◽

pp. 652-657 ◽

Cited By ~ 1

Author(s):

H Takikawa ◽

A Stolz ◽

M Sugimoto ◽

Y Sugiyama ◽

N Kaplowitz

Keyword(s):

Bile Acid ◽

Bile Acids ◽

Glutathione S Transferase ◽

Human Bile

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Pharmacological effects of secondary bile acid microparticles in diabetic murine model

Current Diabetes Reviews ◽

10.2174/1573399816666200626213735 ◽

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.

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