Obeticholic acid improves fetal bile acid profile in a mouse model of gestational hypercholanemia

Pataia, Vanessa; McIlvride, Saraid; Papacleovoulou, Georgia; Ovadia, Caroline; McDonald, Julie A. K.; Wahlström, Annika; Jansen, Eugène; Adorini, Luciano; Shapiro, D. A.; Marchesi, Julian R.; Marschall, Hanns‐Ulrich; Williamson, Catherine

doi:10.1152/ajpgi.00126.2020

Cited by 7 publications

(3 citation statements)

References 52 publications

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“…Changes in gut microbiota in pregnancy were found to be related to the altered intestinal bile acid composition (Ovadia et al, 2019a). In ICP, the bile flow and intestinal bile acid contents might be affected, which in turn influence the gut microbiota (Pataia et al, 2020). UDCA treatment not only enriched bile salt hydrolase-expressing Bacteroidetes, which are essential for bile acid deconjugation (Ovadia et al, 2020), but also reduced the fetomaternal transplacental gradient .…”

Section: Introductionmentioning

confidence: 99%

Alterations of the Human Gut Microbiota in Intrahepatic Cholestasis of Pregnancy

Zhan

Weng

et al. 2021

Front. Cell. Infect. Microbiol.

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Background and AimsWomen with severe intrahepatic cholestasis of pregnancy (ICP) are at higher risks of fetal complications and without effective treatments. Changes in gut microbiota in pregnancy were found to be related to the altered intestinal bile acid composition, so we aimed to explore the alterations of microbiota in the gut of ICP patients.MethodsA total of 90 women were recruited, including 45 ICP patients and 45 healthy controls. The gut microbiota communities of ICP group were compared to control group through 16S ribosomal RNA gene sequencing. The results were then confirmed by real-time polymerase chain reaction (PCR) and generalized linear model (GLM). Furthermore, we analyzed the relationships between microbiota and the severity of ICP.ResultsA total of seven genera and nine taxa with differential abundances between the ICP patients and the controls were identified. All of the seven genera were verified through real-time PCR, and three key genera Parabacteroides, Flavonifractor, and Megamonas were confirmed by using the GLM model. Further analysis found that the genera Escherichia_Shigella, Olsenella, and Turicibacter were enriched in the severe ICP group, the microbial gene function related to biosynthesis of unsaturated fatty acids and propanoate metabolism were also increased in them.ConclusionsOverall, our study was the first in Asia to demonstrate an association between gut microbiota and ICP. Our findings would contribute to a better understanding of the occurrence of ICP.

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Section: Introductionmentioning

confidence: 99%

Alterations of the Human Gut Microbiota in Intrahepatic Cholestasis of Pregnancy

Zhan

Weng

et al. 2021

Front. Cell. Infect. Microbiol.

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“…In C57BL/6J pregnant mouse model fed with cholic acid-enriched diet and OCA plus cholic acid enriched diet, OCA supplementation during gestation was found to have no apparent detrimental impact on maternal and fetal morphometry. The fetal hypercholanemia was greatly ameliorated with OCA ( Pataia et al, 2020 ).…”

Section: Hepatoprotective Agents In the Management Of Icpmentioning

confidence: 99%

Hepatoprotective agents in the management of intrahepatic cholestasis of pregnancy: current knowledge and prospects

Shan,

Dai,

Chen

et al. 2023

Front. Pharmacol.

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Intrahepatic cholestasis of pregnancy (ICP) is characterized by unexplained distressing pruritus in the mother and poses significant risk to the fetus of perinatal mortality. Occurring in the second and third trimester, the serum bile acid and aminotransferase are usually elevated in ICP patients. Ursodeoxycholic acid (UDCA) is the first line drug for ICP but the effectiveness for hepatoprotection is to a certain extent. In ICP patients with severe liver damage, combination use of hepatoprotective agents with UDCA is not uncommon. Herein, we reviewed the current clinical evidence on application of hepatoprotective agents in ICP patients. The underlying physiological mechanisms and their therapeutic effect in clinical practice are summarized. The basic pharmacologic functions of these hepatoprotective medications include detoxification, anti-inflammation, antioxidation and hepatocyte membrane protection. These hepatoprotective agents have versatile therapeutic effects including anti-inflammation, antioxidative stress, elimination of free radicals, anti-steatohepatitis, anti-fibrosis and anti-cirrhosis. They are widely used in hepatitis, non-alcoholic fatty liver disease, drug induced liver injury and cholestasis. Evidence from limited clinical data in ICP patients demonstrate reliable effectiveness and safety of these medications. Currently there is still no consensus on the application of hepatoprotective agents in ICP pregnancies. Dynamic monitoring of liver biochemical parameters and fetal condition is still the key recommendation in the management of ICP pregnancies.

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“…Research into FXR-specific therapeutics for gestational disorders such as ICP or GDM is also currently lacking. However, FXR agonism provides some benefits in mouse models of hypercholanaemia, with improved fetal bile acid profiles (138,139).…”

Section: Bile Acid Receptors and Therapeutics For Gestational Diseasesmentioning

confidence: 99%

ENDOCRINOLOGY IN PREGNANCY: Metabolic impact of bile acids in gestation

Fan

Mitchell

Williamson

2021

European Journal of Endocrinology

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Bile acids are lipid-solubilising molecules that also regulate metabolic processes. Farnesoid X receptor (FXR) and Takeda G-protein coupled receptor 5 (TGR5) are two bile acid receptors with key metabolic roles. FXR regulates bile acid synthesis in the liver and influences bile acid uptake in the intestine. TGR5 is mainly involved in regulation of signalling pathways in response to bile acid uptake in the gut and therefore prandial response. Both FXR and TGR5 have potential as therapeutic targets for disorders of glucose and/or lipid homeostasis. Gestation is also known to cause small increases in bile acid concentrations, but physiological hypercholanaemia of pregnancy is usually not sufficient to cause any clinically relevant effects. This review focuses on how gestation alters bile acid homeostasis, which can become pathological if the elevation of maternal serum bile acids is more marked than physiological hypercholanaemia, and on the influence of FXR and TGR5 function in pregnancy on glucose and lipid metabolism. This will be discussed with reference to two gestational disorders: intrahepatic cholestasis of pregnancy (ICP), a disease where bile acids are pathologically elevated, and gestational diabetes mellitus (GDM), characterised by hyperglycaemia during pregnancy.

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Obeticholic acid improves fetal bile acid profile in a mouse model of gestational hypercholanemia

Cited by 7 publications

References 52 publications

Alterations of the Human Gut Microbiota in Intrahepatic Cholestasis of Pregnancy

Alterations of the Human Gut Microbiota in Intrahepatic Cholestasis of Pregnancy

Hepatoprotective agents in the management of intrahepatic cholestasis of pregnancy: current knowledge and prospects

ENDOCRINOLOGY IN PREGNANCY: Metabolic impact of bile acids in gestation

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