Contributions of bile acids to gastrointestinal physiology as receptor agonists and modifiers of ion channels

Keely, Stephen J.; Urso, Andreacarola; Ilyaskin, Alexandr V.; Korbmacher, Christoph; Bunnett, Nigel W.; Poole, Daniel P.; Carbone, Simona

doi:10.1152/ajpgi.00125.2021

Cited by 18 publications

(15 citation statements)

References 243 publications

(257 reference statements)

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“…Bile acids were physiological detergents that facilitate excretion, absorption, and transport of fats, sterols and other hydrophobic nutrients in the intestine and liver ( Claudel et al., 2005 ). They stimulate bile flow and intestinal motility, regulate lipid secretion and glucose levels, which are essential for the solubilization and absorption of dietary lipids and fat-soluble vitamins ( Keely et al., 2022 ; Mohammed et al., 2022 ). It has been implicated in the regulation of all the key enzymes for cholesterol homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Elucidation of the Reinforcing Spleen Effect of Jujube Fruits Based on Metabolomics and Intestinal Flora Analysis

Yi¹,

Li²,

Guo³

et al. 2022

Front. Cell. Infect. Microbiol.

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Jujube (Ziziphus jujuba Mill.) fruit (JF) is widely consumed as food in Asian countries due to its potential effects for human health. As a traditional Chinese medicine, JF is often used to treat anorexia, fatigue and loose stools caused by spleen deficiency syndromes in China, but the mechanism underlying this effect has not been thoroughly elucidated. In this study, a rat model of spleen deficiency syndromes was adopted to investigate the therapeutic effect of JF extract and its possible mechanism by metabolomics analyses of plasma and urine as well as the intestinal flora analysis. The results showed that the changes in plasma and urine metabolites caused by spleen deficiency were reversed after administration of JF, and these changed endogenous metabolites were mainly involved in retinol metabolism, pentose and glucuronate interconversions, nicotinate and niacinamide metabolism pathways. The 16S rDNA sequencing results showed that JF could regulate intestinal flora imbalance caused by spleen deficiency. The covariance analysis of intestinal flora structure and metabolome indicated that Aerococcus may be a candidate strain for predicting and treating the metabolic pathways of spleen deficiency and related disorders. In summary, it can be revealed that spleen deficiency, which alters metabolic profiles and the intestinal flora, could be alleviated effectively by JF extract.

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Section: Discussionmentioning

confidence: 99%

Elucidation of the Reinforcing Spleen Effect of Jujube Fruits Based on Metabolomics and Intestinal Flora Analysis

Yi¹,

Li²,

Guo³

et al. 2022

Front. Cell. Infect. Microbiol.

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“…BAs in the colon are either passively reabsorbed through the epithelium or excreted in the feces (Hofmann 2009). In recent years, there has been increased interest in the role of BAs as signaling molecules and modulators of epithelial ion transport, particularly in the colon (Kelly et al 2013;Duboc et al 2016;Keely et al 2022). The two primary functions of intestinal epithelial cells are to transport fluid electrolytes and nutrients to and from the gut lumen and to act as a barrier to prevent the entry of harmful substances from the intestinal lumen to the mucosa.…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, TGR5 is expressed on enteric nerves, enterochromaffin cells (ECs), biliary tracts and intestinal epithelium (Keitel et al 2009;Poole et al 2010;Ward et al 2013). The most powerful known endogenous agonists for TGR5 are BAs with the rank order of potency of LCA ≥ DCA > CDCA > CA (Schaap et al 2014;Keely et al 2022). BAs can stimulate or inhibit electrolyte and fluid secretion, depending on the type of BA species and their abundance (Camilleri et al 1980;Devor et al 1993;Barcelo et al 2001;Keely et al 2007;Münch et al 2007;Kelly et al 2013).…”

Section: Methodsmentioning

confidence: 99%

“…At the terminal ileum, most of the conjugated BAs are reabsorbed by the apical sodium-dependent BA transporter (ASBT), and the remaining 5% discharged into the colon. In the colon, primary BAs are metabolized by gut microbiota and by deconjugation, dihydroxylation, and epimerization, to yield secondary BAs (Ridlon et al tion and stimulation of Cl − secretion (Wiemuth et al 2014;Hegyi et al 2018;Keely et al 2022). In vitro studies in cell culture models show that BAs can exert their effects, at least in part, through direct actions on the epithelium itself (Dharmsathaphorn et al 1989;Devor et al 1993;Keely et al 2007).…”

Section: Introductionmentioning

confidence: 99%

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Secondary bile acid lithocholic acid attenuates neurally evoked ion transport in the rat distal colon

et al. 2022

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The inhibitory action of the secondary bile acid lithocholic acid (LCA) on neurally evoked Cl − / HCO 3 − secretion was investigated using the Ussing-chambered mucosal-submucosal preparation from the rat distal colon. Electrical field stimulation (EFS) evoked cholinergic and noncholinergic secretory responses in the rat distal colon. The responses were almost completely blocked by TTX (10 −6 M) but not atropine (10 −5 M) or hexamethonium (10 −4 M). The selective antagonist for VIP receptor 1 (VPAC1) greatly reduced the EFS-evoked response. Thus, the rat distal colon may be predominantly innervated by noncholinergic VIP secretomotor neurons. Basolateral addition of 6 × 10 −5 M LCA inhibited the EFS-evoked response. The inhibitory action of LCA was partly rescued by the Y2R antagonist BIIE0246. The bile acid receptor TGR5 agonist INT-777 mimicked the LCA-induced inhibitory action. Immunohistochemical staining showed the colocalization of TGR5 and PYY on L cells. TGR5 immunoreactivity was also found in VIP-immunoreactive submucosal neurons which also expressed the PYY receptor, Y2R. These results suggest that LCA inhibits neurally evoked Cl − /HCO 3 − secretion through the activation of TGR5 on L cells and cholinergic-and VIP-secretomotor neurons in the submucosal plexus. Furthermore, the inhibitory mechanism may involve TGR5-stimulated PYY release from L cells and Y2R activation in VIP-secretomotor neurons.

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“…Traditionally, bile acids were considered metabolic byproducts of cholesterol metabolism whose sole function was to emulsify fats, thereby aiding their digestion and absorption. Over the past 25 years, the role of bile acids expanded greatly to include prominent functions as signaling molecules within the gut ( 1 ) and other organs ( 2 ). We now appreciate that bile acids may interact functionally with disparate classes of nuclear and plasma membrane receptors and ion transporters expressed by normal and neoplastic cells, thereby modulating important cell functions in health and disease, including gastrointestinal (GI) neoplasia ( 3 ).…”

Section: Bile Acids As Signaling Moleculesmentioning

confidence: 99%

Gastrointestinal neoplasia: carcinogenic interaction between bile acids and Helicobacter pylori in the stomach

Alizadeh¹,

Raufman²

2022

Journal of Clinical Investigation

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Bile acids modulate cell functions in health and disease, however, the mechanisms underlying their actions on neoplastic cells in the gastrointestinal (GI) tract remain largely unknown. In this issue of the JCI , Noto et al. comprehensively analyzed how interactions between Helicobacter pylori infection, iron deficiency, and bile acids modulate gastric inflammation and carcinogenesis. The investigators used sophisticated models, including INS-GAS mice with elevated serum gastrin and gastric acid secretion, in which H . pylori infection mimics human disease progression, to show that selected bile acids potentiated the carcinogenic effects of H . pylori infection and iron depletion. This elegant work has broad translational implications for microbe-associated GI neoplasia. Importantly, bile acid sequestration robustly attenuated the combined effects of H . pylori infection and iron depletion on gastric inflammation and cancer.

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Contributions of bile acids to gastrointestinal physiology as receptor agonists and modifiers of ion channels

Cited by 18 publications

References 243 publications

Elucidation of the Reinforcing Spleen Effect of Jujube Fruits Based on Metabolomics and Intestinal Flora Analysis

Elucidation of the Reinforcing Spleen Effect of Jujube Fruits Based on Metabolomics and Intestinal Flora Analysis

Secondary bile acid lithocholic acid attenuates neurally evoked ion transport in the rat distal colon

Gastrointestinal neoplasia: carcinogenic interaction between bile acids and Helicobacter pylori in the stomach

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