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

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.

Download Full-text

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

Metabolites ◽

10.3390/metabo11020099 ◽

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.

Download Full-text

Effects of Daily Strawberry Intake (4 weeks) on Plasma Bile Acid Composition in Humans: A Randomized, Placebo-Controlled, Crossover Trial

Current Developments in Nutrition ◽

10.1093/cdn/nzaa055_038 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 1153-1153 ◽

Cited By ~ 1

Author(s):

Anqi Zhao ◽

Liyun Zhang ◽

Xuhuiqun Zhang ◽

Indika Edirisinghe ◽

Britt Burton-Freeman ◽

...

Keyword(s):

Bile Acid ◽

Bile Acids ◽

Crossover Trial ◽

Solid Phase ◽

Lithocholic Acid ◽

Statistical Significance ◽

Bile Acid Metabolism ◽

Plasma Samples ◽

Nutrition Research ◽

Freeze Dried

Abstract Objectives Bile acids (BA) are liver derived compounds that undergo host and microbial metabolism. BA metabolites have multiple physiological roles including maintaining intestinal immune homeostasis. Dietary components influence BA metabolism/excretion through several mechanisms. This study aimed to evaluate the effects of daily strawberry intake (4 weeks) on bile acid metabolism in humans. Methods Thirty overweight/obese adults (age: 53 ± 7 years, BMI: 31 ± 4 kg/m,2) were recruited for this randomized, double-blind, placebo-controlled, crossover trial. Participants were randomized to 1 of 2 study sequences in a 1:1 ratio with 4 weeks washout period between two treatments. Participants consumed a strawberry beverage containing 25 g freeze-dried strawberry powder (∼1.75 servings of fresh strawberries) or energy-matched control beverage in random order twice a day for 4 weeks. Fasting blood samples were collected at weeks 0, 4, 8, and 12. Plasma samples (500 μL) were extracted using solid-phase C18 cartridges. An ultra-high performance liquid chromatography tandem mass spectrometry method was developed to quantitate bile acids and their metabolites (sulfates, glucuronides) in plasma. The method was validated in terms of linearity, sensitivity, recovery, and matrix effect. The data were analyzed using a paired student t-test with statistical significance set at P < 0.05. Results Twenty-nine glucuronidated and sulfated BAs were identified in plasma samples. Concentrations of primary BAs were not affected between the study treatments, whereas a significant decrease (P < 0.05) was observed in total secondary BAs (52 compounds) after 4 weeks of strawberry intake (11.2 ± 1.1 µmol/L) compared to placebo (18.3 ± 3.2 µmol/L). Individual secondary BAs including lithocholic acid (LCA), sulfo-glycolithocholic acid, and C24 oxidized LCA were significantly decreased after 4-week strawberry intake compared to placebo (P < 0.05). Conclusions Our results indicate that regular strawberry intake could lower pro-inflammatory LCA and other secondary BAs, suggesting a potential role of strawberry in ameliorating colonic inflammation and promoting gut health. Funding Sources This work was funded by the California Strawberry Commission and various donor funds to the Center for Nutrition Research, IIT.

Download Full-text

Three probiotic strains exert different effects on plasma bile acid profiles in healthy obese adults: randomised, double-blind placebo-controlled crossover study

Beneficial Microbes ◽

10.3920/bm2018.0151 ◽

2019 ◽

Vol 10 (5) ◽

pp. 497-509 ◽

Cited By ~ 5

Author(s):

T. Culpepper ◽

C.C. Rowe ◽

C.T. Rusch ◽

A.M. Burns ◽

A.P. Federico ◽

...

Keyword(s):

Bile Acid ◽

Glucose Metabolism ◽

Crossover Study ◽

Bile Acids ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Bile Acid Metabolism ◽

Double Blind ◽

Human Bile ◽

Probiotic Strains

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.

Download Full-text

Effect of tartaric acid and dietary fibre from sun-dried raisins on colonic function and on bile acid and volatile fatty acid excretion in healthy adults

British Journal Of Nutrition ◽

10.1079/bjn2003966 ◽

2003 ◽

Vol 90 (4) ◽

pp. 803-807 ◽

Cited By ~ 36

Author(s):

Gene A. Spiller ◽

Jon A. Story ◽

Emily J. Furumoto ◽

Jo Carol Chezem ◽

Monica Spiller

Keyword(s):

Fatty Acid ◽

Bile Acid ◽

Bile Acids ◽

Tartaric Acid ◽

Transit Time ◽

Dietary Fibre ◽

Healthy Adults ◽

Intestinal Transit ◽

Intestinal Transit Time ◽

Potential Health

Sun-dried raisins are a source of dietary fibre and tartaric acid. The effects of tartaric acid on colon function have not been the focus of extensive research. The purpose of the present study was to evaluate the effects of dietary fibre and tartaric acid from sun-dried raisins on colon function and on faecal bile acid and short-chain fatty acid (SCFA) excretion in healthy adults. Thirteen healthy subjects were fed 120 g sun-dried raisins/d or 5 g cream of tartar (equivalent to the tartaric acid in 120 g sun-dried raisins)/d for 9 weeks, divided into 3-week cycles. The experimental diets were fed in a crossover design after an initial control period. Faeces were collected for the last 4 d of each cycle for analysis of SCFA and bile acids. Intestinal transit time decreased from 42h on the baseline diet to 31h on cream of tartar (P<0·1) and to 28h on sun-dried raisins (P<0·05). Faeces were softer on both sun-dried raisins and cream of tartar, but sun-dried raisins increased faecal wet weight (P<0·05), while cream of tartar did not. Sun-dried raisins caused significant reductions from baseline values in total bile acid concentration (from 1·42 (sd 1·03) to 1·09 (sd 0·76) mg/g, P<0·05), whereas cream of tartar did not (1·40 (sd 1·06) mg/g). Sun-dried raisins also significantly reduced the lithocholic (LC):deoxylithocholic acid (DC) ratio (from 1·63 (sd 0·85) to 1·09 (sd 0·50), P<0·02), whereas cream of tartar reduced the ratio, but to a lesser extent (1·29 (sd 0·79), NS). Both faecal bile acids and the LC:DC ratio are indicators of reduced risk for colon cancer. Sun-dried raisins increased total SCFA excretion (from 5·6 (sd 3·4) to 7·6 (sd 3·0) g/4d, P<0·05), which remained unchanged with cream of tartar (5·6 (sd 3·0) g/4d). Both sun-dried raisins and cream of tartar appear to be good stool softeners and to shorten intestinal transit time, although the fibre in sun-dried raisins has the added benefit of increasing faecal weight. Both sun-dried raisins and cream of tartar modulate the composition of faecal bile acids and SCFA in a way that has potential health benefits.

Download Full-text

Identification and Distribution of Sterols, Bile Acids, and Acylcarnitines by LC–MS/MS in Humans, Mice, and Pigs—A Qualitative Analysis

Metabolites ◽

10.3390/metabo12010049 ◽

2022 ◽

Vol 12 (1) ◽

pp. 49

Author(s):

Ambrin Farizah Babu ◽

Ville Mikael Koistinen ◽

Soile Turunen ◽

Gloria Solano-Aguilar ◽

Joseph F. Urban ◽

...

Keyword(s):

Mass Spectrometry ◽

Bile Acid ◽

Bile Acids ◽

Biological Samples ◽

Simultaneous Detection ◽

Reversed Phase ◽

Proximal Colon ◽

Low Concentrations ◽

Human Stool ◽

Mouse Ileum

Sterols, bile acids, and acylcarnitines are key players in human metabolism. Precise annotations of these metabolites with mass spectrometry analytics are challenging because of the presence of several isomers and stereoisomers, variability in ionization, and their relatively low concentrations in biological samples. Herein, we present a sensitive and simple qualitative LC–MS/MS (liquid chromatography with tandem mass spectrometry) method by utilizing a set of pure chemical standards to facilitate the identification and distribution of sterols, bile acids, and acylcarnitines in biological samples including human stool and plasma; mouse ileum, cecum, jejunum content, duodenum content, and liver; and pig bile, proximal colon, cecum, heart, stool, and liver. With this method, we detected 24 sterol, 32 bile acid, and 27 acylcarnitine standards in one analysis that were separated within 13 min by reversed-phase chromatography. Further, we observed different sterol, bile acid, and acylcarnitine profiles for the different biological samples across the different species. The simultaneous detection and annotation of sterols, bile acids, and acylcarnitines from reference standards and biological samples with high precision represents a valuable tool for screening these metabolites in routine scientific research.

Download Full-text

Studies on bile acids: The microquantitative separation of cellular bile acids by gas-liquid chromatography

Biochemical Journal ◽

10.1042/bj1020654 ◽

1967 ◽

Vol 102 (3) ◽

pp. 654-659 ◽

Cited By ~ 53

Author(s):

T Okishio ◽

P.N. Padmanabhan ◽

G Maureen

Keyword(s):

Liquid Chromatography ◽

Bile Acid ◽

Bile Acids ◽

Methyl Esters ◽

Peptide Bond ◽

Anion Exchange Chromatography ◽

Exchange Chromatography ◽

Gas Liquid Chromatography ◽

Chemical Hydrolysis ◽

Freeze Dried

1. A method is described for the quantitative isolation of bile acids from cellular material. Homogenates of rat liver are freeze-dried and extracted exhaustively with 95% (v/v) ethanol containing 0.1% (v/v) of aq. ammonia (sp.gr. 0.88) and purified by anion-exchange chromatography on Amberlyst A-26. 2. The extracted bile acid conjugates are subjected to either of two hydrolytic procedures, one involving chemical and the other enzymic agents. A unique feature in this study is the introduction of an enzyme, a clostridial peptide-bond hydrolase, for the rapid cleavage of bile acid conjugates, replacing the classical drastic chemical hydrolysis with strong alkali. 3. After hydrolysis, free bile acids are methylated and converted into their trifluoroacetates for final determination by gas-liquid chromatography on a triple component column, FS-1265-SE30-NGS. 4. For the purpose of identification of peaks, bile acid methyl esters are converted into their trimethylsilyl ethers by allowing the methyl esters to react with a new and potent silyl donor, bis(trimethylsilyl)acetamide. 5. The technique affords us a means of studying the metabolism of bile acids at the cellular and subcellular levels in tissues.

Download Full-text

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

Pflügers Archiv - European Journal of Physiology ◽

10.1007/s00424-018-2142-z ◽

2018 ◽

Vol 470 (7) ◽

pp. 1087-1102 ◽

Cited By ~ 2

Author(s):

Alexandr V. Ilyaskin ◽

Sonja A. Kirsch ◽

Rainer A. Böckmann ◽

Heinrich Sticht ◽

Christoph Korbmacher ◽

...

Keyword(s):

Bile Acid ◽

Ion Channel ◽

Bile Acids ◽

Human Bile ◽

Channel Inhibition

Download Full-text

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.

Download Full-text