Bile acids as metabolic regulators: an update

Li, Tiangang; Chiang, John Y.L.

doi:10.1097/mog.0000000000000934

Cited by 6 publications

(4 citation statements)

References 49 publications

(76 reference statements)

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“…Bile acids are a group of complex molecules derived from cholesterol, primarily synthesized in the liver and secreted into the small intestine (132). They play a crucial role in the digestion and absorption of lipids and fat-soluble vitamins.…”

Section: Bile Acid Synthesized By Gut Microbiota In Ardsmentioning

confidence: 99%

Gut microbiota and its metabolic products in acute respiratory distress syndrome

Zhang,

Lu,

Dong

et al. 2024

Front. Immunol.

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The prevalence rate of acute respiratory distress syndrome (ARDS) is estimated at approximately 10% in critically ill patients worldwide, with the mortality rate ranging from 17% to 39%. Currently, ARDS mortality is usually higher in patients with COVID-19, giving another challenge for ARDS treatment. However, the treatment efficacy for ARDS is far from satisfactory. The relationship between the gut microbiota and ARDS has been substantiated by relevant scientific studies. ARDS not only changes the distribution of gut microbiota, but also influences intestinal mucosal barrier through the alteration of gut microbiota. The modulation of gut microbiota can impact the onset and progression of ARDS by triggering dysfunctions in inflammatory response and immune cells, oxidative stress, cell apoptosis, autophagy, pyroptosis, and ferroptosis mechanisms. Meanwhile, ARDS may also influence the distribution of metabolic products of gut microbiota. In this review, we focus on the impact of ARDS on gut microbiota and how the alteration of gut microbiota further influences the immune function, cellular functions and related signaling pathways during ARDS. The roles of gut microbiota-derived metabolites in the development and occurrence of ARDS are also discussed.

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Section: Bile Acid Synthesized By Gut Microbiota In Ardsmentioning

confidence: 99%

Gut microbiota and its metabolic products in acute respiratory distress syndrome

Zhang,

Lu,

Dong

et al. 2024

Front. Immunol.

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“…Firmicutes bacteria, particularly strains belonging to the genus Clostridium , play an important role in the dehydroxylation process. They produce BA 7α-dehydroxylase that converts primary BAs (CA and CDCA) into secondary BAs (DCA, LCA)[ 47 , 48 ]. The main bacteria involved in BA oxidation are from the genera: Bacteroides , Clostridium , Eubacterium , Escherichia , Eggerthella , Peptostreptococcus , and Ruminococcus .…”

Section: Gut-liver Axis and Related Pathophysiologymentioning

confidence: 99%

“…strain S2 , produce sulfatases that can increase the desulfation of BAs. Desulfation of BAs by intestinal bacteria helps with the reabsorption of BAs and is crucial for maintaining homeostasis in the BAs pool[ 48 , 50 ]. Disruption of BA metabolism occurs during the development of NAFLD, leading to a characteristic pattern of BAs in patients with NASH.…”

Section: Gut-liver Axis and Related Pathophysiologymentioning

confidence: 99%

Role of gut-liver axis and glucagon-like peptide-1 receptor agonists in the treatment of metabolic dysfunction-associated fatty liver disease

Rochoń,

Kalinowski,

Szymanek-Majchrzak

et al. 2024

World J Gastroenterol

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Metabolic dysfunction-associated fatty liver disease (MAFLD) is a hepatic manifestation of the metabolic syndrome. It is one of the most common liver diseases worldwide and shows increasing prevalence rates in most countries. MAFLD is a progressive disease with the most severe cases presenting as advanced fibrosis or cirrhosis with an increased risk of hepatocellular carcinoma. Gut microbiota play a significant role in the pathogenesis and progression of MAFLD by disrupting the gut-liver axis. The mechanisms involved in maintaining gut-liver axis homeostasis are complex. One critical aspect involves preserving an appropriate intestinal barrier permeability and levels of intestinal lumen metabolites to ensure gut-liver axis functionality. An increase in intestinal barrier permeability induces metabolic endotoxemia that leads to steatohepatitis. Moreover, alterations in the absorption of various metabolites can affect liver metabolism and induce liver steatosis and fibrosis. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a class of drugs developed for the treatment of type 2 diabetes mellitus. They are also commonly used to combat obesity and have been proven to be effective in reversing hepatic steatosis. The mechanisms reported to be involved in this effect include an improved regulation of glycemia, reduced lipid synthesis, β-oxidation of free fatty acids, and induction of autophagy in hepatic cells. Recently, multiple peptide receptor agonists have been introduced and are expected to increase the effectiveness of the treatment. A modulation of gut microbiota has also been observed with the use of these drugs that may contribute to the amelioration of MAFLD. This review presents the current understanding of the role of the gut-liver axis in the development of MAFLD and use of members of the GLP-1 RA family as pleiotropic agents in the treatment of MAFLD.

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“…In addition to their classical function in the absorption of dietary fat-soluble nutrients and vitamins, bile acids (BAs) have been identified as signaling molecules involved in the regulation of lipid, glucose and energy metabolism and the modulation of immune responses [ 1 ]. Their action on metabolism is manifested through the activation of several intracellular nuclear receptors, such as the farnesoid X receptor (FXR/NR1H4), pregnane X receptor (PXR/NR1I2), vitamin D receptor (VDR) and the constitutive androstane receptor (CAR/NR1I3), as well as cell surface G protein-coupled receptors (GPCRs), such as the Takeda G protein-coupled receptor 5 (TGR5/GPBAR1).…”

Section: Introductionmentioning

confidence: 99%

Bile Acid Sequestration via Colesevelam Reduces Bile Acid Hydrophobicity and Improves Liver Pathology in Cyp2c70−/− Mice with a Human-like Bile Acid Composition

Palmiotti,

de Vries,

Hovingh

et al. 2023

Biomedicines

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Bile acids (BAs) and their signaling pathways have been identified as therapeutic targets for liver and metabolic diseases. We generated Cyp2c70−/− (KO) mice that were not able to convert chenodeoxycholic acid into rodent-specific muricholic acids (MCAs) and, hence, possessed a more hydrophobic, human-like BA pool. Recently, we have shown that KO mice display cholangiopathic features with the development of liver fibrosis. The aim of this study was to determine whether BA sequestration modulates liver pathology in Western type-diet (WTD)-fed KO mice. The BA sequestrant colesevelam was mixed into the WTD (2% w/w) of male Cyp2c70+/+ (WT) and KO mice and the effects were evaluated after 3 weeks of treatment. Colesevelam increased fecal BA excretion in WT and KO mice and reduced the hydrophobicity of biliary BAs in KO mice. Colesevelam ameliorated diet-induced hepatic steatosis in WT mice, whereas KO mice were resistant to diet-induced steatosis and BA sequestration had no additional effects on liver fat content. Total cholesterol concentrations in livers of colesevelam-treated WT and KO mice were significantly lower than those of untreated controls. Of particular note, colesevelam treatment normalized plasma levels of liver damage markers in KO mice and markedly decreased hepatic mRNA levels of fibrogenesis-related genes in KO mice. Lastly, colesevelam did not affect glucose excursions and insulin sensitivity in WT or KO mice. Our data show that BA sequestration ameliorates liver pathology in Cyp2c70−/− mice with a human-like bile acid composition without affecting insulin sensitivity.

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Bile acids as metabolic regulators: an update

Cited by 6 publications

References 49 publications

Gut microbiota and its metabolic products in acute respiratory distress syndrome

Gut microbiota and its metabolic products in acute respiratory distress syndrome

Role of gut-liver axis and glucagon-like peptide-1 receptor agonists in the treatment of metabolic dysfunction-associated fatty liver disease

Bile Acid Sequestration via Colesevelam Reduces Bile Acid Hydrophobicity and Improves Liver Pathology in Cyp2c70−/− Mice with a Human-like Bile Acid Composition

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