Bile Acids, Their Receptors, and the Gut Microbiota

Poland, James C; Flynn, Charles R.

doi:10.1152/physiol.00028.2020

Cited by 41 publications

(31 citation statements)

References 177 publications

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“…BAs are released from the gallbladder into the small intestine postprandially in response to the hormone, cholecystokinin (CCK) [ 16 ]. Once in the small intestine, BAs emulsify dietary fat and enhance lipid, sterol, and vitamin absorption [ 16 ]. Most of the BA remain in the gut lumen until they reach the TI.…”

Section: Bile Acidsmentioning

confidence: 99%

“…This receptor is found on the basolateral membrane of enterocytes. The BA will travel back into the liver through the sodium taurocholate cotransporting polypeptide (NTCP) transporter [ 16 , 17 ]. Once in the liver, free BA is reconjugated with taurine or glycine before secretion into the biliary tract and intestinal lumen [ 12 ].…”

Section: Bile Acidsmentioning

confidence: 99%

“…Once in the liver, free BA is reconjugated with taurine or glycine before secretion into the biliary tract and intestinal lumen [ 12 ]. This metabolic loop constitutes the enterohepatic cycle of BA [ 6 ] and occurs 8–10 times per day [ 16 ]. This recycling is necessary as hepatocytes have limited capability to produce BAs [ 18 ].…”

Section: Bile Acidsmentioning

confidence: 99%

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Bile Acids and the Microbiome: Making Sense of This Dynamic Relationship in Their Role and Management in Crohn’s Disease

Kumar

Al-Hassi

Steed

et al. 2022

Canadian Journal of Gastroenterology and Hepatology

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Background. Bile acids help maintain the physiological balance of the gut microbiome and the integrity of the intestinal epithelial barrier. Similarly, intestinal bacteria play a major role in bile acid metabolism as they are involved in crucial biotransformation steps in the enterohepatic circulation pathway. Understanding the relationship between bile acid signalling and the gut microbiome in Crohn’s disease can help target new and innovative treatment strategies. Aims. This review summarises the relationship between bile acids and the microbiome in Crohn’s disease and discusses potential novel therapeutic options. Methods. We performed a literature review on bile acid signalling, its effect on the gut microbiome, and therapeutic applications in Crohn’s disease. Results. Current research suggests that there is a strong interplay between the dysregulated microbiota, bile acid metabolism, and the mucosal immune system that can result in a changed immunological function, triggering the inflammatory response in Crohn’s disease. Recent studies have demonstrated an association with altering the enterohepatic circulation and activating the farnesoid X receptor signalling pathway with the use of probiotics and faecal microbial transplantation, respectively. Bile acid sequestrants have been shown to have anti-inflammatory, cytoprotective, and anti-apoptotic properties with the potential to alter the intestinal microbial composition, suggesting a possible role in inducing and maintaining Crohn’s disease. Conclusions. Active Crohn’s disease has been correlated with changes in bacterial concentrations, which may be associated with changes in bile acid modification. Further research should focus on targeting these areas for future therapeutic options.

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Section: Bile Acidsmentioning

confidence: 99%

Section: Bile Acidsmentioning

confidence: 99%

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Bile Acids and the Microbiome: Making Sense of This Dynamic Relationship in Their Role and Management in Crohn’s Disease

Kumar

Al-Hassi

Steed

et al. 2022

Canadian Journal of Gastroenterology and Hepatology

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“…were significantly disturbed during THBSS progression, which were closely related to the inflammation and hemorheology and coagulation abnormalities (the main manifestations in model rats during the progression of THBSS) (Xu et al, 2017). It is reported that bile acids are important signal molecules in energy metabolism and can affect coagulation through farnesol receptor X (Poland and Flynn 2021). Phospholipids play important roles in inflammation, hemorheology, coagulation, and microcirculation (Deguchi et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Elucidation of the Mechanisms and Effective Substances of Paeoniae Radix Rubra Against Toxic Heat and Blood Stasis Syndrome With a Stage-Oriented Strategy

Wang

et al. 2022

Front. Pharmacol.

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In the clinical practice of traditional Chinese medicine, toxic heat and blood stasis syndrome (THBSS) is a common syndrome observed in various critical diseases. Paeoniae Radix Rubra (PRR) has known therapeutic effects on THBSS. However, its pharmacodynamic mechanisms and effective substances in the treatment of THBSS still need further elucidation. Our previous study indicated that THBSS had three stages of progression, and the abnormal biochemical indices of each stage were different. Therefore, this study aimed to elucidate the pharmacodynamic mechanisms and effective substances of PRR for the treatment of THBSS with a stage-oriented strategy. Specifically, research was performed separately in two stable stages of THBSS: the excessive heat and little blood stasis (EHLBS) and blood stasis (BS) stages. THBSS model rats, at different time periods after syndrome initiation (first 5 h for EHLBS and 24 h later for BS), were used to conduct the two-stage investigation. Targeted metabonomics analysis was performed to elucidate the pharmacodynamic mechanisms of PRR in the treatment of EHLBS or BS. Based on the relationship between the individual differences in blood drug concentrations and pharmacodynamic effects, partial least squares regression analysis was employed to screen for the effective substances from the original constituents and metabolites of PRR. We found that PRR could upregulate primary bile acid biosynthesis, glycerophospholipid metabolism, ether lipid metabolism, and five amino acid metabolic pathways (e.g., arginine and proline metabolism) to treat EHLBS. Meanwhile, PRR alleviated BS by upregulating primary bile acid biosynthesis and downregulating glycerophospholipid metabolism. But PRR had no obvious effects on ether lipid metabolism and amino acid metabolism in this stage. In total, 17 and 9 potential effective substances were found in the EHLBS and BS stages, respectively, among which there were only five common compounds between the two stages. To our knowledge, sixteen compounds were regarded as potential effective substances of PRR for the first time. Therefore, the pharmacodynamic mechanisms and effective substances of PRR in the treatment of EHLBS and BS were partly different. Overall, this stage-oriented strategy provides a new way to study the pharmacodynamic mechanisms and effective substances of traditional Chinese drugs.

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“…On the one hand, intestinal dysbiosis and subsequent disruption of intestinal barrier allow the translocation of inflammatory factors, pathogens and pathogen-associated molecular patterns (PAMPs) into the portal vein and systemic circulations, which further interact with hepatic stellate cells (HSCs) and immune cells in livers and dysregulate hepatic functions. On the other hand, gut microbiota contributes to the deconjugation, oxidation, epimerization, 7-dehydroxylation, esterification and desulfation of BAs, which serve as imperative gateway reactions in BA metabolism and cause a vicious cycle of hepatoenteral injury [ 5 , 6 ]. The increased BAs are sensed by intestinal farnesoid X receptor (FXR) to induce mouse fibroblast growth factor 15 (FGF15, FGF19 in humans), which binds to FGF receptor 4 (FGFR4) on hepatocytes and feedback inhibits BA biogenesis [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Si-Wu-Tang ameliorates fibrotic liver injury via modulating intestinal microbiota and bile acid homeostasis

Xue

Ding

et al. 2021

Chin Med

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Background Fibrotic liver injury is a progressive scarring event, which may permanently affect liver function and progress into devastating end-stage liver diseases due to the absence of effective therapies. Si-Wu-Tang (SWT), a traditional Chinese medicine formula used in clinic to treat gynecological disorders for centuries, has been investigated in recent preliminary findings for its role in alleviating chronic liver diseases. Here we aim to elucidate the therapeutic effects and possible mechanisms of SWT against fibrotic liver injury. Methods UHPLC-MS/MS was performed to investigate the chemical characterization of SWT. After intragastrically administered with carbon tetrachloride (CCl4) every 3 days for 1-week, C57BL/6 mice were orally administered with SWT (5.2, 10.4 and 20.8 g/kg) once daily for 3 weeks along with CCl4 challenge. Liver function was determined by the measurement of serum biomarkers, hematoxylin and eosin (H&E) and Masson’s trichrome staining. Intestinal inflammatory infiltration and the disruption of intestinal barrier were examined by H&E and E-cadherin immunohistochemical staining. The microbial composition of intestinal content was determined by 16S rRNA sequencing. Serum bile acids (BAs) profiling was analyzed by LC–MS/MS. Simultaneously, the expression of genes of interest was determined by qPCR and western blot. Results SWT exhibited remarkable therapeutic effects on CCl4-induced liver fibrosis, as indicated by improved collagen accumulation in livers, intestinal barrier injury and hepatic and intestinal inflammatory response. Results of 16S rRNA sequencing revealed that SWT treatment strikingly restructured intestinal microbiota in fibrotic mice by increasing the relative abundances of Bacteroides and Lachnoclostridium and decreasing the relative abundances of Alistipes and Rikenellaceae. UHPLC-MS/MS data suggested that SWT altered the composition of BAs in circulation as evidenced by increased unconjugated BAs like cholic acid and chenodeoxycholic acid but decreased conjugated BAs including taurocholic acid and taurodeoxycholic acid, compared to that in CCl4 mice. Notably, SWT efficiently improved the imbalance of BA homeostasis in livers caused by CCl4 via activating farnesoid X receptor (FXR)-fibroblast growth factor 15 enterohepatic and FXR-small heterodimer partner hepatic pathways. Conclusion SWT decreased inflammatory response, reconstructed gut microbiota-mediated BA homeostasis as well as activated FXR pathways, which eventually protected against CCl4-induced fibrotic liver injury.

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Bile Acids, Their Receptors, and the Gut Microbiota

Cited by 41 publications

References 177 publications

Bile Acids and the Microbiome: Making Sense of This Dynamic Relationship in Their Role and Management in Crohn’s Disease

Bile Acids and the Microbiome: Making Sense of This Dynamic Relationship in Their Role and Management in Crohn’s Disease

Elucidation of the Mechanisms and Effective Substances of Paeoniae Radix Rubra Against Toxic Heat and Blood Stasis Syndrome With a Stage-Oriented Strategy

Si-Wu-Tang ameliorates fibrotic liver injury via modulating intestinal microbiota and bile acid homeostasis

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