Bile Acids, Gut Microbiome and the Road to Fatty Liver Disease

2021 ◽  
pp. 2719-2730
Author(s):  
Phillip B. Hylemon ◽  
Lianyong Su ◽  
Po‐Cheng Zheng ◽  
Jasmohan S. Bajaj ◽  
Huiping Zhou
Hepatology ◽  
2021 ◽  
Author(s):  
Suet‐Ying Kwan ◽  
Jingjing Jiao ◽  
Aron Joon ◽  
Peng Wei ◽  
Lauren E. Petty ◽  
...  

Author(s):  
Jiake Yu ◽  
Hu Zhang ◽  
Liya Chen ◽  
Yufei Ruan ◽  
Yiping Chen ◽  
...  

Children with nonalcoholic fatty liver disease (NAFLD) display an altered gut microbiota compared with healthy children. However, little is known about the fecal bile acid profiles and their association with gut microbiota dysbiosis in pediatric NAFLD. A total of 68 children were enrolled in this study, including 32 NAFLD patients and 36 healthy children. Fecal samples were collected and analyzed by metagenomic sequencing to determine the changes in the gut microbiota of children with NAFLD, and an ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) system was used to quantify the concentrations of primary and secondary bile acids. The associations between the gut microbiota and concentrations of primary and secondary bile acids in the fecal samples were then analyzed. We found that children with NAFLD exhibited reduced levels of secondary bile acids and alterations in bile acid biotransforming-related bacteria in the feces. Notably, the decrease in Eubacterium and Ruminococcaceae bacteria, which express bile salt hydrolase and 7α-dehydroxylase, was significantly positively correlated with the level of fecal lithocholic acid (LCA). However, the level of fecal LCA was negatively associated with the abundance of the potential pathogen Escherichia coli that was enriched in children with NAFLD. Pediatric NAFLD is characterized by an altered profile of gut microbiota and fecal bile acids. This study demonstrates that the disease-associated gut microbiota is linked with decreased concentrations of secondary bile acids in the feces. The disease-associated gut microbiota likely inhibits the conversion of primary to secondary bile acids.


Doctor Ru ◽  
2020 ◽  
Vol 19 (7) ◽  
pp. 21-30
Author(s):  
N.B. Gubergritz ◽  
◽  
N.V. Belyaeva ◽  
T.L. Mozhina ◽  
N.E. Monogarova ◽  
...  

Objective of the Review: to analyse changes in bile acids (BA) metabolism due to nonalcoholic fatty liver disease (NAFL), nonalcoholic fatty pancreas disease (NAFP); to assess the efficiency of ursodeoxycholic acid (UDCA) for their correction. Key Points. NAFL and NAFP have much in common, including BA synthesis imbalance and reduced farnesoid X receptor (FXR) expression. One possible therapy of NAFL and NAFP is BA synthesis correction and increase in FXR expression using FXR agonists. The article discusses clinical and experimental trials of the efficiency of selective FXR agonist — UDCA — in NAFL and NAFP. Conclusion. The multifactorial UDCA mechanism of action including anti-inflammatory, antioxidant, cytoprotective and antiapoptotic actions, can normalise carbohydrate, lipid metabolism and activate FXR; it can justify medicine inclusion into NAFL and NAFP therapeutic regimens. Keywords: nonalcoholic fatty liver disease, nonalcoholic fatty pancreas disease, ursodeoxycholic acid.


2020 ◽  
Vol 9 (5) ◽  
pp. 1369 ◽  
Author(s):  
Paula Iruzubieta ◽  
Juan M. Medina ◽  
Raúl Fernández-López ◽  
Javier Crespo ◽  
Fernando de la Cruz

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disease in which environmental and genetic factors are involved. Although the molecular mechanisms involved in NAFLD onset and progression are not completely understood, the gut microbiome (GM) is thought to play a key role in the process, influencing multiple physiological functions. GM alterations in diversity and composition directly impact disease states with an inflammatory course, such as non-alcoholic steatohepatitis (NASH). However, how the GM influences liver disease susceptibility is largely unknown. Similarly, the impact of strategies targeting the GM for the treatment of NASH remains to be evaluated. This review provides a broad insight into the role of gut microbiota in NASH pathogenesis, as a diagnostic tool, and as a therapeutic target in this liver disease. We highlight the idea that the balance in metabolic fermentations can be key in maintaining liver homeostasis. We propose that an overabundance of alcohol-fermentation pathways in the GM may outcompete healthier, acid-producing members of the microbiota. In this way, GM ecology may precipitate a self-sustaining vicious cycle, boosting liver disease progression.


2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Caihua Wang ◽  
Chunpeng Zhu ◽  
Liming Shao ◽  
Jun Ye ◽  
Yimin Shen ◽  
...  

Nonalcoholic fatty liver disease (NAFLD) is a major health threat around the world and is characterized by dysbiosis. Primary bile acids are synthesized in the liver and converted into secondary bile acids by gut microbiota. Recent studies support the role of bile acids in modulating dysbiosis and NAFLD, while the mechanisms are not well elucidated. Dysbiosis may alter the size and the composition of the bile acid pool, resulting in reduced signaling of bile acid receptors such as farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5). These receptors are essential in lipid and glucose metabolism, and impaired bile acid signaling may cause NAFLD. Bile acids also reciprocally regulate the gut microbiota directly via antibacterial activity and indirectly via FXR. Therefore, bile acid signaling is closely linked to dysbiosis and NAFLD. During the past decade, stimulation of bile acid receptors with their agonists has been extensively explored for the treatment of NAFLD in both animal models and clinical trials. Early evidence has suggested the potential of bile acid receptor agonists in NAFLD management, but their long-term safety and effectiveness need further clarification.


2019 ◽  
Vol 156 (6) ◽  
pp. S-1295-S-1296
Author(s):  
Rohini Mehta ◽  
James Paik ◽  
Sean C. Felix ◽  
Hussain Allawi ◽  
Ingrid Schneider ◽  
...  

Gut Microbes ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 882-899 ◽  
Author(s):  
Na Young Lee ◽  
Sang Jun Yoon ◽  
Dae Hee Han ◽  
Haripriya Gupta ◽  
Gi Soo Youn ◽  
...  

PLoS ONE ◽  
2016 ◽  
Vol 11 (5) ◽  
pp. e0151829 ◽  
Author(s):  
Marialena Mouzaki ◽  
Alice Y. Wang ◽  
Robert Bandsma ◽  
Elena M. Comelli ◽  
Bianca M. Arendt ◽  
...  

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