Farnesoid X Receptor, Bile Acid Metabolism, and Gut Microbiota

Mori, Hideki; Baroni, G. Svegliati; Marzioni, Marco; Nicola, F Di; Santori, Pierangelo; Maroni, Luca; Abenavoli, Ludovico; Scarpellini, Emidio

doi:10.3390/metabo12070647

Cited by 31 publications

(21 citation statements)

References 73 publications

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“…The gut microbiota is another crucial modulator in controlling BA homeostasis by linking the circulation of BAs between the liver and gut ( Jiang et al, 2022 ). Bile salt hydrolase (BSH) activity is essential for the deconjugation of primary BAs by gut microbiota ( Mori et al, 2022 ) and is mostly facilitated by Gram-positive bacteria, such as Lactobacillus ( Jayashree et al, 2014 ), Bifidobacterium ( Kim et al, 2005 ), Enterococcus ( Wijaya et al, 2004 ), and Clostridium spp. ( Rossocha et al, 2005 ) as well as in commensal Gram-negative Bacteroides spp.…”

Section: Introductionmentioning

confidence: 99%

Kuhuang alleviates liver fibrosis by modulating gut microbiota-mediated hepatic IFN signaling and bile acid synthesis

Shen

Zhou

et al. 2022

Front. Pharmacol.

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Background: Liver fibrosis is a common outcome of the pathological progression of chronic liver disease; however, no specific and effective therapeutic agent has been approved for its treatment. We investigated the effects of Kuhuang on liver fibrosis and the underlying mechanisms of action.Materials and methods: To induce hepatic fibrosis, either 3,5-diethoxycarbonyl-1,4-dihydro-collidine (DDC) diet was administered, or bile duct ligation (BDL) surgery was performed on C57BL/6 mice. Kuhuang was orally administered to mice for 7 days before and after bile duct ligation or 4 weeks with a DDC diet. Hematoxylin and eosin, Sirius red staining, and immunohistochemical analyses were performed to evaluate hepatic pathology. Hepatic interferon-β (IFN-β) levels were measured using an enzyme-linked immunosorbent assay. RNA sequencing was performed to examine the gene expression profiles of liver tissues. The mRNA expression of inflammatory, profibrotic, and bile acid (BA)-related genes was further validated by qRT-PCR. A targeted metabolomics assay revealed the alteration of the hepatic bile acid (BA) composition. The composition of the gut microbiota was determined via 16S rRNA sequencing.Results: Treatment with Kuhuang attenuated liver fibrosis and reduced the inflammatory response in bile duct ligation and DDC mouse models. In addition, the hepatic IFN signaling pathway was activated following Kuhuang treatment. Kuhuang treatment also significantly decreased hepatic levels of both primary and secondary BAs. In addition, Kuhuang treatment altered gut microbiota composition, with an increased abundance of interferon-inducing Akkermansia and decreased abundance of bile salt hydrolase-producing Lactobacillus, Clostridium, and Bifidobacterium. Furthermore, the abundance of Akkermansia was positively correlated with the hepatic mRNA expression levels of Ifna4, Ifnb, and Isg15, whereas that of Lactobacillus, Clostridium-sensu-stricto-1, and Bifidobacterium was positively correlated with levels of bile acid synthesis-related genes.Conclusion: Our results suggest that Kuhuang plays a protective role during the progression of liver fibrosis, potentially by altering the composition of the gut microbiota, which consequently activates interferon signaling and inhibits bile acid synthesis in the liver.

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Section: Introductionmentioning

confidence: 99%

Kuhuang alleviates liver fibrosis by modulating gut microbiota-mediated hepatic IFN signaling and bile acid synthesis

Shen

Zhou

et al. 2022

Front. Pharmacol.

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“…At the same time, the liver function of patients with fatty liver has been damaged, and the ability to metabolize fat has decreased, resulting in the deposition of large amounts of lipids in the liver and blood circulation, which will increase triglycerides in the blood (34). Therefore, high blood triglyceride levels are likely to cause fatty changes in the liver, thereby increasing the incidence of NAFLD (35). LDL is a lipoprotein particle that carries cholesterol into peripheral tissue cells and can become oxidized (36).…”

Section: Discussionmentioning

confidence: 99%

Relationship between obesity related indicators and non-alcoholic fatty liver disease in children: a systematic review and meta-analysis

He¹,

Cao²,

Zhou³

et al. 2023

Transl Pediatr

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Background: The incidence of childhood obesity is increasing. There is some controversy about the association between overweight and nonalcoholic fatty liver disease (NAFLD) in children. This article intends to compare the differences in these obesity related parameters between NAFLD children and healthy control children through meta-analysis to provide evidence-based medical evidence for clinical use. Methods:The literature were extracted from English and Chinese databases. Statistical analysis was performed using Stata/SE 16.0, IBM SPSS Statistics 26, and Review Manager 5.4 software.Results: A total of 15 original case control studies were included, including 12 high-quality literature, 3 medium quality literature. The total sample size included in the analysis was 1,595 children, including 824 in the experimental group and 771 in the control group. The results of meta-analysis showed that the body mass index (BMI) of the NAFLD group was significantly higher than that of the control group [mean difference (MD) =1.05, 95% confidence interval (CI): 0.36-1.73]. Waist circumference of the NAFLD group was significantly larger than that of the control group (MD =1.66, 95% CI: 0.60-2.73). Triglyceride level in the NAFLD group was significantly higher than that in the control group (MD =1.08, 95% CI: 0.05-2.12). Low-density lipoprotein (LDL) level in the NAFLD group was significantly higher than that in the control group (MD =0.49, 95% CI: 0.12-0.85). In addition, fasting blood glucose of the NAFLD group was significantly higher than that of the control group (MD =0.31, 95% CI: 0.09-0.54) and insulin resistance index of the NAFLD group was significantly higher than that of the control group (MD =2.95, 95% CI:1.41-4.49). Exercise had a significant effect on improving the degree of NAFLD in children [odds ratio (OR) =2.51, 95% CI: 1.83-3.43].Conclusions: Various physical indicators were related to obesity, including BMI, waist circumference, triglyceride content, LDL, fasting blood glucose, and insulin resistance index, and all were significantly correlated with NAFLD in children, provided a reference for future clinical diagnosis and treatment work.In addition, exercise could significantly improve the degree of steatosis in children with NAFLD.

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“…Increased insulin sensitivity and decreased hepatic gluconeogenesis and circulating triglyceride concentration are the results of BA binding to the FXR [ 170 ]. Dysbiosis in the gut microbiota may alter the ratio of primary to secondary BAs which, in turn, could disrupt FXR signaling resulting in significant effects on host metabolism [ 171 ]. An imbalance between secondary and primary BAs causes dysregulation of lipid and glucose metabolism [ 172 ] as a result of a reduction in signaling via the BA receptor FXR [ 173 ].…”

Section: Gut–liver Axis and Nafldmentioning

confidence: 99%

Gut–Liver Axis and Non-Alcoholic Fatty Liver Disease: A Vicious Circle of Dysfunctions Orchestrated by the Gut Microbiome

Pezzino

Sofia

Faletra

et al. 2022

Biology

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Non-alcoholic fatty liver disease (NAFLD) is a prevalent, multifactorial, and poorly understood liver disease with an increasing incidence worldwide. NAFLD is typically asymptomatic and coupled with other symptoms of metabolic syndrome. The prevalence of NAFLD is rising in tandem with the prevalence of obesity. In the Western hemisphere, NAFLD is one of the most prevalent causes of liver disease and liver transplantation. Recent research suggests that gut microbiome dysbiosis may play a significant role in the pathogenesis of NAFLD by dysregulating the gut–liver axis. The so-called “gut–liver axis” refers to the communication and feedback loop between the digestive system and the liver. Several pathological mechanisms characterized the alteration of the gut–liver axis, such as the impairment of the gut barrier and the increase of the intestinal permeability which result in endotoxemia and inflammation, and changes in bile acid profiles and metabolite levels produced by the gut microbiome. This review will explore the role of gut–liver axis disruption, mediated by gut microbiome dysbiosis, on NAFLD development.

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Farnesoid X Receptor, Bile Acid Metabolism, and Gut Microbiota

Cited by 31 publications

References 73 publications

Kuhuang alleviates liver fibrosis by modulating gut microbiota-mediated hepatic IFN signaling and bile acid synthesis

Kuhuang alleviates liver fibrosis by modulating gut microbiota-mediated hepatic IFN signaling and bile acid synthesis

Relationship between obesity related indicators and non-alcoholic fatty liver disease in children: a systematic review and meta-analysis

Gut–Liver Axis and Non-Alcoholic Fatty Liver Disease: A Vicious Circle of Dysfunctions Orchestrated by the Gut Microbiome

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