Mechanisms of Interactions between Bile Acids and Plant Compounds—A Review

Plant compounds are described to interact with bile acids during small intestinal digestion. This review will summarise mechanisms of interaction between bile acids and plant compounds, challenges in in vivo and in vitro analyses, and possible consequences on health. The main mechanisms of interaction assume that increased viscosity during digestion results in reduced micellar mobility of bile acids, or that bile acids and plant compounds are associated or complexed at the molecular level. Increasing viscosity during digestion due to specific dietary fibres is considered a central reason for bile acid retention. Furthermore, hydrophobic interactions are proposed to contribute to bile acid retention in the small intestine. Although frequently hypothesised, no mechanism of permanent binding of bile acids by dietary fibres or indigestible protein fractions has yet been demonstrated. Otherwise, various polyphenolic structures were recently associated with reduced micellar solubility and modification of steroid and bile acid excretion but underlying molecular mechanisms of interaction are not yet fully understood. Therefore, future research activities need to consider the complex composition and cell-wall structures as influenced by processing when investigating bile acid interactions. Furthermore, influences of bile acid interactions on gut microbiota need to be addressed to clarify their role in bile acid metabolism.

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Bile acid metabolism is altered in multiple sclerosis and supplementation ameliorates neuroinflammation

10.1101/627356 ◽

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.

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Retention of Primary Bile Acids by Lupin Cell Wall Polysaccharides Under In Vitro Digestion Conditions

Nutrients ◽

10.3390/nu11092117 ◽

2019 ◽

Vol 11 (9) ◽

pp. 2117 ◽

Cited By ~ 3

Author(s):

Naumann ◽

Schweiggert-Weisz ◽

Haller ◽

Eisner

Keyword(s):

Cell Wall ◽

Bile Acid ◽

Bile Acids ◽

Molecular Interactions ◽

Enterohepatic Circulation ◽

In Vitro Digestion ◽

Adsorptive Capacity ◽

Cell Wall Polysaccharides ◽

Dietary Fibres

Interference of dietary fibres with the enterohepatic circulation of bile acids is proposed as a mechanism for lowering cholesterol. We investigated how lupin hull and cotyledon dietary fibres interact with primary bile acids using an in vitro model under simulated upper gastrointestinal conditions. Cell wall polysaccharides were isolated and extracted to separate pectin-like, hemicellulosic, and lignocellulosic structures. Lupin hull consisted mainly of structural components rich in cellulose. The viscosity of the in vitro digesta of lupin hull was low, showing predominantly liquid-like viscoelastic properties. On the other hand, lupin cotyledon fibre retarded bile acid release due to increased viscosity of the in vitro digesta, which was linked with high contents of pectic polymers forming an entangled network. Molecular interactions with bile acids were not measured for the hull but for the cotyledon, as follows: A total of 1.29 µmol/100 mg DM of chenodesoxycholic acids were adsorbed. Molecular interactions of cholic and chenodesoxycholic acids were evident for lignin reference material but did not account for the adsorption of the lupin cotyledon. Furthermore, none of the isolated and fractionated cell wall materials showed a significant adsorptive capacity, thus disproving a major role of lupin cell wall polysaccharides in bile acid adsorption.

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A model screening pipeline for bile acid converting anti-Clostridioides difficile bacteria reveals unique biotherapeutic potential of Peptacetobacter hiranonis

10.1101/2021.09.29.462466 ◽

2021 ◽

Author(s):

Akhil A. Vinithakumari ◽

Belen G. Hernandez ◽

Sudeep Ghimire ◽

Seidu Adams ◽

Caroline Stokes ◽

...

Keyword(s):

Bile Acid ◽

Bile Acids ◽

Fecal Microbiota Transplantation ◽

Bile Acid Metabolism ◽

In Vitro Tests ◽

Essential Information ◽

Clostridioides Difficile ◽

Gut Colonization

Clostridioides difficile is an antibiotic-resistant bacterium that causes serious, toxin-mediated enteric disease in humans and animals. Gut dysbiosis and resultant alterations in the intestinal bile acid profile play an important role in the pathogenesis of C. difficile infection (CDI). Restoration of the gut microbiota and re-establishment of bacterial bile acid metabolism using fecal microbiota transplantation (FMT) has been established as a promising strategy against this disease, although this method has several limitations. Thus, a more defined and precise microbiota-based approach using bacteria that biotransform primary bile acids into secondary bile acids could effectively overcome these limitations and control CDI. Therefore, a screening pipeline was developed to isolate bile acid converting bacteria from fecal samples. Dogs were selected as a model CDI-resistant microbiota donor for this pipeline, which yielded a novel Peptacetobacter hiranonis strain that possesses unique anti-C. difficile properties, and both bile acid deconjugation and 7-α dehydroxylating activities to perform bile acid conversion. The screening pipeline included a set of in vitro tests along with a precision in vivo gut colonization and bile acid conversion test using altered Schadler flora (ASF) colonized mice. In addition, this pipeline also provided essential information on the growth requirements for screening and cultivating the candidate bacterium, its survival in a CDI predisposing environment, and potential pathogenicity. The model pipeline documented here yielded multiple bile acid converting bacteria, including a P. hiranonis isolate with unique anti-C. difficile biotherapeutic potential, which can be further tested in subsequent preclinical and human clinical trials.

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Differentiation of Adsorptive and Viscous Effects of Dietary Fibres on Bile Acid Release by Means of In Vitro Digestion and Dialysis

International Journal of Molecular Sciences ◽

10.3390/ijms19082193 ◽

2018 ◽

Vol 19 (8) ◽

pp. 2193 ◽

Cited By ~ 16

Author(s):

Susanne Naumann ◽

Ute Schweiggert-Weisz ◽

Stephanie Bader-Mittermaier ◽

Dirk Haller ◽

Peter Eisner

Keyword(s):

Bile Acid ◽

Bile Acids ◽

Dry Matter ◽

Taurocholic Acid ◽

Viscous Effects ◽

Dietary Fibres ◽

High Fibre ◽

Dialysis Method ◽

Acid Release

To explain the cholesterol-reducing effects of dietary fibres, one of the major mechanisms proposed is the reduced reabsorption of bile acids in the ileum. The interaction of dietary fibres with bile acids is associated with their viscous or adsorptive effects. Since these fibre characteristics are difficult to investigate in vivo, suitable in vitro methodologies can contribute to understanding the mechanistic principles. We compared the commonly used centrifugal approach with a modified dialysis method using dietary fibre-rich materials from different sources (i.e., barley, citrus, lupin, and potato). Digestion was simulated in vitro with oral, gastric, and small intestinal digestion environments. The chyme was dialysed and released bile acids were analysed by high-performance liquid chromatography. The centrifugation method showed adsorptive effects only for cholestyramine (reference material) and a high-fibre barley product (1.4 µmol taurocholic acid/100 mg dry matter). Alternatively, the dialysis approach showed higher values of bile acid adsorption (2.3 µmol taurocholic acid/100 mg dry matter) for the high-fibre barley product. This indicated an underestimated adsorption when using the centrifugation method. The results also confirmed that the dialysis method can be used to understand the influence of viscosity on bile acid release. This may be due to entrapment of bile acids in the viscous chyme matrix. Further studies on fibre structure and mechanisms responsible for viscous effects are required to understand the formation of entangled networks responsible for the entrapment of the bile acids.

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Bile Acids in Polycystic Liver Diseases: Triggers of Disease Progression and Potential Solution for Treatment

Digestive Diseases ◽

10.1159/000450989 ◽

2017 ◽

Vol 35 (3) ◽

pp. 275-281 ◽

Cited By ~ 5

Author(s):

Maria J. Perugorria ◽

Ibone Labiano ◽

Aitor Esparza-Baquer ◽

Marco Marzioni ◽

Jose J.G. Marin ◽

...

Keyword(s):

Bile Acid ◽

Bile Acids ◽

Liver Diseases ◽

Molecular Mechanisms ◽

Pharmacological Therapy ◽

Polycystic Kidney ◽

Beneficial Effects ◽

Polycystic Liver

Polycystic liver diseases (PLDs) are a group of genetic hereditary cholangiopathies characterized by the development and progressive growth of cysts in the liver, which are the main cause of morbidity. Current therapies are based on surgical procedures and pharmacological strategies, which show short-term and modest beneficial effects. Therefore, the determination of the molecular mechanisms of pathogenesis appears to be crucial in order to find new potential targets for pharmacological therapy. Ductal plate malformation during embryogenesis and abnormal cystic cholangiocyte growth and secretion are some of the key mechanisms involved in the pathogenesis of PLDs. However, the discovery of the presence of bile acids in the fluid collected from human cysts and the intrahepatic accumulation of cytotoxic bile acids in an animal model of PLD (i.e. polycystic kidney (PCK) rat) suggest a potential role of impaired bile acid homeostasis in the pathogenesis of these diseases. On the other hand, ursodeoxycholic acid (UDCA) has emerged as a new potential therapeutic tool for PLDs by promoting the inhibition of cystic cholangiocyte growth in both PCK rats and highly symptomatic patients with autosomal dominant polycystic kidney disease (ADPKD: most common type of PLD), and improving symptoms. Chronic treatment with UDCA normalizes the decreased intracellular calcium levels in ADPKD human cholangiocytes in vitro, which results in the reduction of their baseline-stimulated proliferation. Moreover, UDCA decreases the liver concentration of cytotoxic bile acids in PCK rats and the bile acid-dependent enhanced proliferation of cystic cholangiocytes. Here, the role of bile acids in the pathogenesis of PLDs and the potential therapeutic value of UDCA for the treatment of these diseases are reviewed and future lines of investigation in this field are proposed.

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Total flavonoids of Astragalus Ameliorated Bile Acid Metabolism Dysfunction in Diabetes Mellitus

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/6675567 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Zhe Wang ◽

Xu-Ling Li ◽

Kin-Fong Hong ◽

Ting-Ting Zhao ◽

Rui-Xue Dong ◽

...

Keyword(s):

Lipid Metabolism ◽

Bile Acid ◽

Bile Acids ◽

Glucose Transporter ◽

Density Lipoprotein ◽

Bile Acid Metabolism ◽

Active Components ◽

Glucose Transporter 2

Astragalus Radix is one of the common traditional Chinese medicines used to treat diabetes. However, the underlying mechanism is not fully understood. Flavones are a class of active components that have been reported to exert various activities. Existing evidence suggests that flavones from Astragalus Radix may be pivotal in modulating progression of diabetes. In this study, total flavones from Astragalus Radix (TFA) were studied to observe its effects on metabolism of bile acids both in vivo and in vitro. C57BL/6J mice were treated with STZ and high-fat feeding to construct diabetic model, and HepG2 cell line was applied to investigate the influence of TFA on liver cells. We found a serious disturbance of bile acids and lipid metabolism in diabetic mice, and oral administration or cell incubation with TFA significantly reduced the production of total cholesterol (TCHO), total triglyceride, glutamic oxalacetic transaminase (AST), glutamic-pyruvic transaminase (ALT), and low-density lipoprotein (LDL-C), while it increased the level of high-density lipoprotein (HDL-C). The expression of glucose transporter 2 (GLUT2) and cholesterol 7α-hydroxylase (CYP7A1) was significantly upregulated on TFA treatment, and FXR and TGR5 play pivotal role in modulating bile acid and lipid metabolism. This study supplied a novel understanding towards the mechanism of Astragalus Radix on controlling diabetes.

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Manipulating the Microbiome: An Alternative Treatment for Bile Acid Diarrhoea

Microbiology Research ◽

10.3390/microbiolres12020023 ◽

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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Liver Bile Acid Changes in Mouse Models of Alzheimer’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22147451 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7451

Author(s):

Harpreet Kaur ◽

Drew Seeger ◽

Svetlana Golovko ◽

Mikhail Golovko ◽

Colin Kelly Combs

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Bile Acid ◽

Bile Acids ◽

Cholesterol Metabolism ◽

Amyloid Β ◽

Acid Synthesis ◽

Bile Acid Synthesis ◽

Liver Cholesterol ◽

Bile Acid Metabolism

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment. It is hypothesized to develop due to the dysfunction of two major proteins, amyloid-β (Aβ) and microtubule-associated protein, tau. Evidence supports the involvement of cholesterol changes in both the generation and deposition of Aβ. This study was performed to better understand the role of liver cholesterol and bile acid metabolism in the pathophysiology of AD. We used male and female wild-type control (C57BL/6J) mice to compare to two well-characterized amyloidosis models of AD, APP/PS1, and AppNL-G-F. Both conjugated and unconjugated primary and secondary bile acids were quantified using UPLC-MS/MS from livers of control and AD mice. We also measured cholesterol and its metabolites and identified changes in levels of proteins associated with bile acid synthesis and signaling. We observed sex differences in liver cholesterol levels accompanied by differences in levels of synthesis intermediates and conjugated and unconjugated liver primary bile acids in both APP/PS1 and AppNL-G-F mice when compared to controls. Our data revealed fundamental deficiencies in cholesterol metabolism and bile acid synthesis in the livers of two different AD mouse lines. These findings strengthen the involvement of liver metabolism in the pathophysiology of AD.

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