-
1.
The Bioavailability and Biological Activities of Phytosterols as Modulators of Cholesterol Metabolism.
Li, X, Xin, Y, Mo, Y, Marozik, P, He, T, Guo, H
Molecules (Basel, Switzerland). 2022;(2)
Abstract
Phytosterols are natural sterols widely found in plants that have a variety of physiological functions, and their role in reducing cholesterol absorption has garnered much attention. Although the bioavailability of phytosterols is only 0.5-2%, they can still promote cholesterol balance in the body. A mechanism of phytosterols for lowering cholesterol has now been proposed. They not only reduce the uptake of cholesterol in the intestinal lumen and affect its transport, but also regulate the metabolism of cholesterol in the liver. In addition, phytosterols can significantly reduce the plasma concentration of total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C), with a dose-response relationship. Ingestion of 3 g of phytosterols per day can reach the platform period, and this dose can reduce LDL-C by about 10.7%. On the other hand, phytosterols can also activate the liver X receptor α-CPY7A1 mediated bile acids excretion pathway and accelerate the transformation and metabolism of cholesterol. This article reviews the research progress of phytosterols as a molecular regulator of cholesterol and the mechanism of action for this pharmacological effect.
-
2.
Aberrant Gut-To-Brain Signaling in Irritable Bowel Syndrome - The Role of Bile Acids.
Ní Dhonnabháín, R, Xiao, Q, O'Malley, D
Frontiers in endocrinology. 2021;:745190
Abstract
Functional bowel disorders such as irritable bowel syndrome (IBS) are common, multifactorial and have a major impact on the quality of life of individuals diagnosed with the condition. Heterogeneity in symptom manifestation, which includes changes in bowel habit and visceral pain sensitivity, are an indication of the complexity of the underlying pathophysiology. It is accepted that dysfunctional gut-brain communication, which incorporates efferent and afferent branches of the peripheral nervous system, circulating endocrine hormones and local paracrine and neurocrine factors, such as host and microbially-derived signaling molecules, underpins symptom manifestation. This review will focus on the potential role of hepatic bile acids in modulating gut-to-brain signaling in IBS patients. Bile acids are amphipathic molecules synthesized in the liver, which facilitate digestion and absorption of dietary lipids. They are also important bioactive signaling molecules however, binding to bile acid receptors which are expressed on many different cell types. Bile acids have potent anti-microbial actions and thereby shape intestinal bacterial profiles. In turn, bacteria with bile salt hydrolase activity initiate the critical first step in transforming primary bile acids into secondary bile acids. Individuals with IBS are reported to have altered microbial profiles and modified bile acid pools. We have assessed the evidence to support a role for bile acids in the pathophysiology underlying the manifestation of IBS symptoms.
-
3.
Bile Acids as Key Modulators of the Brain-Gut-Microbiota Axis in Alzheimer's Disease.
Mulak, A
Journal of Alzheimer's disease : JAD. 2021;(2):461-477
-
-
Free full text
-
Abstract
Recently, the concept of the brain-gut-microbiota (BGM) axis disturbances in the pathogenesis of Alzheimer's disease (AD) has been receiving growing attention. At the same time, accumulating data revealing complex interplay between bile acids (BAs), gut microbiota, and host metabolism have shed new light on a potential impact of BAs on the BGM axis. The crosstalk between BAs and gut microbiota is based on reciprocal interactions since microbiota determines BA metabolism, while BAs affect gut microbiota composition. Secondary BAs as microbe-derived neuroactive molecules may affect each of three main routes through which interactions within the BGM axis occur including neural, immune, and neuroendocrine pathways. BAs participate in the regulation of multiple gut-derived molecule release since their receptors are expressed on various cells. The presence of BAs and their receptors in the brain implies a direct effect of BAs on the regulation of neurological functions. Experimental and clinical data confirm that disturbances in BA signaling are present in the course of AD. Disturbed ratio of primary to secondary BAs as well as alterations in BA concertation in serum and brain samples have been reported. An age-related shift in the gut microbiota composition associated with its decreased diversity and stability observed in AD patients may significantly affect BA metabolism and signaling. Given recent evidence on BA neuroprotective and anti-inflammatory effects, new therapeutic targets have been explored including gut microbiota modulation by probiotics and dietary interventions, ursodeoxycholic acid supplementation, and use of BA receptor agonists.
-
4.
Role of Bile Acids in the Regulation of Food Intake, and Their Dysregulation in Metabolic Disease.
Xie, C, Huang, W, Young, RL, Jones, KL, Horowitz, M, Rayner, CK, Wu, T
Nutrients. 2021;(4)
Abstract
Bile acids are cholesterol-derived metabolites with a well-established role in the digestion and absorption of dietary fat. More recently, the discovery of bile acids as natural ligands for the nuclear farnesoid X receptor (FXR) and membrane Takeda G-protein-coupled receptor 5 (TGR5), and the recognition of the effects of FXR and TGR5 signaling have led to a paradigm shift in knowledge regarding bile acid physiology and metabolic health. Bile acids are now recognized as signaling molecules that orchestrate blood glucose, lipid and energy metabolism. Changes in FXR and/or TGR5 signaling modulates the secretion of gastrointestinal hormones including glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), hepatic gluconeogenesis, glycogen synthesis, energy expenditure, and the composition of the gut microbiome. These effects may contribute to the metabolic benefits of bile acid sequestrants, metformin, and bariatric surgery. This review focuses on the role of bile acids in energy intake and body weight, particularly their effects on gastrointestinal hormone secretion, the changes in obesity and T2D, and their potential relevance to the management of metabolic disorders.
-
5.
Bile Acids: Key Regulators and Novel Treatment Targets for Type 2 Diabetes.
Wu, Y, Zhou, A, Tang, L, Lei, Y, Tang, B, Zhang, L
Journal of diabetes research. 2020;:6138438
Abstract
Type 2 diabetes mellitus (T2DM), characterized by insulin resistance and unclear pathogenesis, is a serious menace to human health. Bile acids are the end products of cholesterol catabolism and play an important role in maintaining cholesterol homeostasis. Furthermore, increasing studies suggest that bile acids may regulate glucose tolerance, insulin sensitivity, and energy metabolism, suggesting that bile acids may represent a potential therapeutic target for T2DM. This study summarizes the metabolism of bile acids and, more importantly, changes in their concentrations, constitution, and receptors in diabetes. Furthermore, we provide an overview of the mechanisms underlying the role of bile acids in glucose and lipid metabolism, as well as the occurrence and development of T2DM. Bile acid-targeted therapy may represent a valid approach for T2DM treatment.
-
6.
Bile acids mediated potential functional interaction between FXR and FATP5 in the regulation of Lipid Metabolism.
Kumari, A, Pal Pathak, D, Asthana, S
International journal of biological sciences. 2020;(13):2308-2322
Abstract
Perturbation in lipid homeostasis is one of the major bottlenecks in metabolic diseases, especially Non-alcoholic Fatty Liver Disease (NAFLD), which has emerged as a leading global cause of chronic liver disease. The bile acids (BAs) and their derivatives exert a variety of metabolic effects through complex and intertwined pathways, thus becoming the attractive target for metabolic syndrome treatment. To modulate the lipid homeostasis, the role of BAs, turn out to be paramount as it is essential for the absorption, transport of dietary lipids, regulation of metabolic enzymes and transporters that are essential for lipid modulation, flux, and excretion. The synthesis and transport of BAs (conjugated and unconjugated) is chiefly controlled by nuclear receptors and the uptake of long-chain fatty acids (LCFA) and BA conjugation via transporters. Among them, from in-vivo studies, farnesoid X receptor (FXR) and liver-specific fatty acid transport protein 5 (FATP5) have shown convincing evidence for their key roles in lipid homeostasis and reversal of fatty liver disease substantially. BAs have a wider range of biological effects as they are identified as modulators for FXR and FATP5 both and therefore hold a significant promise for altering the lipid content in the treatment of a metabolic disorder. BAs also have received noteworthy interest in drug delivery research due to its peculiar physicochemical properties and biocompatibility. Here, we are highlighting the connecting possibility of BAs as an agonist for FXR and antagonist for FATP5, paving an avenue to target them for designing synthetic small molecules for lipid homeostasis.
-
7.
The Role of Bile Acids in Chronic Diarrhea.
Camilleri, M, Vijayvargiya, P
The American journal of gastroenterology. 2020;(10):1596-1603
-
-
Free full text
-
Abstract
Bile acids (BAs) are the central signals in enterohepatic communication, and they also integrate microbiota-derived signals into enterohepatic signaling. The tissue distribution and signaling pathways activated by BAs through natural receptors, farsenoid X receptor and G protein-coupled BA receptor 1 (GPBAR1, also known as Takeda G-coupled receptor 5), have led to a greater understanding of the mechanisms and potential therapeutic agents. BA diarrhea is most commonly encountered in ileal resection or disease, in idiopathic disorders (with presentation similar to functional diarrhea or irritable bowel syndrome with diarrhea), and in association with malabsorption such as chronic pancreatitis or celiac disease. Diagnosis of BA diarrhea is based on Se-homocholic acid taurine retention, 48-hour fecal BA excretion, or serum 7αC4; the latter being a marker of hepatic BA synthesis. BA diarrhea tends to be associated with higher body mass index, increased stool weight and stool fat, and acceleration of colonic transit. Biochemical markers of increased BA synthesis or excretion are available through reference laboratories. Current treatment of BA diarrhea is based on BA sequestrants, and, in the future, it is anticipated that farsenoid X receptor agonists may also be effective. The optimal conditions for an empiric trial with BA sequestrants as a diagnostic test are still unclear. However, such therapeutic trials are widely used in clinical practice. Some national guidelines recommend definitive diagnosis of BA diarrhea over empirical trial.
-
8.
Bile acid homeostasis in gastrointestinal and metabolic complications of cystic fibrosis.
van de Peppel, IP, Bodewes, FAJA, Verkade, HJ, Jonker, JW
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society. 2019;(3):313-320
Abstract
With the improved treatment of the pulmonary complications of cystic fibrosis (CF), gastrointestinal problems have become more important in the morbidity in CF. A hallmark of the gastrointestinal phenotype of CF, apart from pancreatic insufficiency, is a disruption of bile acid homeostasis. Bile acid homeostasis is important for many gastrointestinal processes including fat absorption, inflammation, microbial composition, as well as regulation of whole body energy metabolism. This review describes the impairment of bile acid homeostasis in CF, its possible consequences for gastrointestinal and metabolic complications and its potential as a target for therapy.
-
9.
Gallbladder bile supersaturated with cholesterol in gallstone patients preferentially develops from shortage of bile acids.
Rudling, M, Laskar, A, Straniero, S
Journal of lipid research. 2019;(3):498-505
Abstract
Gallstone (GS) formation requires that bile is supersaturated with cholesterol, which is estimated by a cholesterol saturation index (CSI) calculated from gallbladder (GB) total lipids and the mol% (mole percent) of bile acids (BAs), cholesterol, and phospholipids (PLs). Whereas CSI indicates GS risk, we hypothesized that additional comparisons of GB lipid mol% data are inappropriate to identify why CSI is increased in GS disease. We anticipated that GB lipid mmol/l (millimole per liter) levels should instead identify that, and therefore retrieved GB mmol/l data for BAs, cholesterol, and PLs from a study on 145 GS and 87 GS-free patients and compared them with the corresponding mol% data. BA and PL mmol/l levels were 33% and 31% lower in GS patients, while cholesterol was unaltered. CSI was higher in GS patients and correlated inversely with GB levels of BAs and PLs, but not with cholesterol. A literature search confirmed, in 13 studies from 11 countries, that GB BA levels and, to a certain extent, PLs are strongly reduced in GS patients, while cholesterol levels are not elevated. Our findings show that a shortage of BAs is a major reason why GB bile is supersaturated with cholesterol in GS patients. These results are sustainable because they are also valid from a global perspective.
-
10.
Microbial metabolites in non-alcoholic fatty liver disease.
Zhou, D, Fan, JG
World journal of gastroenterology. 2019;(17):2019-2028
Abstract
The prevalence of non-alcoholic fatty liver disease (NAFLD) is rising exponentially worldwide. The spectrum of NAFLD includes non-alcoholic fatty liver, non-alcoholic steatohepatitis, liver cirrhosis, and even hepatocellular carcinoma. Evidence shows that microbial metabolites play pivotal roles in the onset and progression of NAFLD. In this review, we discuss how microbe-derived metabolites, such as short-chain fatty acids, endogenous ethanol, bile acids and so forth, contribute to the pathogenesis of NAFLD.