scholarly journals Alterations in bile acid metabolizing gut microbiota and specific bile acid genes as a precision medicine to subclassify NAFLD

2021 ◽  
Author(s):  
Na Jiao ◽  
Rohit Loomba ◽  
Zi-Huan Yang ◽  
Dingfeng Wu ◽  
Sa Fang ◽  
...  
Keyword(s):  
Bile Acid ◽  
Precision Medicine ◽  
Validation Cohort ◽  
Statistical Tests ◽  
Alcoholic Fatty Liver ◽  
Disease Markers ◽  
Microbial Associations ◽  
Metagenome Sequencing ◽  
Post Hoc ◽  
Alcoholic Fatty Liver Disease

Multiple mechanisms for the gut microbiome contributing to the pathogenesis of non-alcoholic fatty liver disease (NAFLD) have been implicated. Here, weaim to investigate the contribution and potential application for altered bile acids (BA) metabolizing microbesin NAFLD by post-hoc analysis of whole metagenome sequencing (WMS) data. The discovery cohort consisted of 86 well-characterized biopsy-proven NAFLD patients and 38 healthy controls. Assembly-based analysis was performed to identify BA-metabolizing microbes. Statistical tests, feature selection and microbial co-abundance analysis were integrated to identify microbial alterations and markers in NAFLD. An independent validation cohort was subjected to similar analyses. NAFLD microbiota exhibited decreased diversity and microbial associations. We established a classifier model with 53 differential species exhibiting a robust diagnostic accuracy (AUC=0.97) for dectecting NAFLD. Next, eight important differential pathway markers including secondary BA biosynthesis were identified. Specifically, increased abundance of 7α-HSDH, baiA and baiB were detected in NAFLD. Further, 10 of 50 BA-metabolizing metagenome-assembled genomes (MAGs) from Bacteroides ovatusand Eubacterium biforme, were dominant in NAFLD and interplayed as a synergetic ecological guild. Importantly, two subtypes of NAFLD patients were observed according to secondary BA metabolism potentials. Elevated capability for secondary BA biosynthesis was also observed in the validation cohort. These bacterial BA-metabolizing genes and microbes identified in this study may serve as disease markers. Microbial differences in BA-metabolism and strain-specific differences among patients highlight the potential for precision medicine in NAFLD treatment.

scholarly journals Alterations in bile acid metabolizing gut microbiota and specific bile acid genes as a precision medicine to subclassify NAFLD

2020 ◽  
Author(s):  
Na Jiao ◽  
Rohit Loomba ◽  
Zi-Huan Yang ◽  
Dingfeng Wu ◽  
Sa Fang ◽  
...  
Keyword(s):  
Bile Acid ◽  
Precision Medicine ◽  
Validation Cohort ◽  
Interaction Analysis ◽  
Statistical Tests ◽  
Microbial Interactions ◽  
Alcoholic Fatty Liver ◽  
Disease Markers ◽  
Metagenome Sequencing ◽  
Alcoholic Fatty Liver Disease

AbstractBackground & AimsMultiple mechanisms for the gut microbiome contributing to the pathogenesis of non-alcoholic fatty liver disease (NAFLD) have been implicated. Here, we aim to investigate the contribution and potential application for altered bile acid (BA) metabolizing microbe in NAFLD using whole metagenome sequencing (WMS) data.Methods86 well-characterized biopsy-proven NAFLD patients and 38 healthy controls were included in the discovery cohort. Assembly-based analysis was performed to identify BA-metabolizing microbes. Statistical tests, feature selection and microbial interaction analysis were integrated to identify microbial alterations and markers in NAFLD. An independent validation cohort was subjected to similar analyses.ResultsNAFLD microbiota exhibited decreased diversity and microbial interactions. We established a classifier model with 53 differential species exhibiting a robust diagnostic accuracy (AUC=0.97) for dectecting NAFLD. Next, 8 important differential pathway markers including secondary BA biosynthesis were identified. Specifically, increased abundance of 7α-HSDH, baiA and baiB were detected in NAFLD. Further, 10 of 50 BA-metabolizing metagenome-assembled genomes (MAG)s, from Bacteroides ovatus and Eubacterium biforme, were dominant in NAFLD and interplayed as a synergetic ecological guild. Importantly, two subtypes of NAFLD patients were observed according to secondary BA metabolism potentials. Elevated capability for secondary BA biosynthesis was also observed in the validation cohort.ConclusionsWe identified novel bacterial BA-metabolizing genes and microbes that may contribute to NAFLD pathogenesis and serve as disease markers. Microbial differences in BA-metabolism and strain-specific differences among patients highlight the potential for precision medicine in NAFLD treatment.

scholarly journals Bile Acid and Fibroblast Growth Factor 19 Regulation in Obese Diabetics, and Non-Alcoholic Fatty Liver Disease after Sleeve Gastrectomy

2019 ◽  
Vol 8 (6) ◽  
pp. 815 ◽  
Author(s):  
Hsien-Hao Huang ◽  
Wei-Jei Lee ◽  
Shu-Chun Chen ◽  
Tung-Fang Chen ◽  
Shou-Dong Lee ◽  
...  
Keyword(s):  
Bile Acid ◽  
Fatty Liver ◽  
Bile Acids ◽  
Fatty Liver Disease ◽  
Total Bile Acid ◽  
Alcoholic Fatty Liver ◽  
Liver Index ◽  
Fatty Liver Index ◽  
Total Bile Acids ◽  
Alcoholic Fatty Liver Disease

Background: Sleeve gastrectomy (SG) is an effective treatment for obesity and type 2 diabetes mellitus (T2DM), and non-alcoholic fatty liver disease (NAFLD); however, the mechanism is not completely understood. Bile acids and fibroblast growth factors (FGFs) are involved in the regulation of energy metabolism. Methods: We investigated the roles of total bile acid and FGF 19 in T2DM remission and NAFLD improvement in obese subjects undergoing SG. A total of 18 patients with obesity and T2DM undergoing laparoscopic SG were enrolled in this study. Serial plasma total bile acid and FGF 19 levels were measured, while the fatty liver index was calculated before and after surgery. Results: The FGF 19 level significantly increased, and the total bile acid level and fatty liver index decreased 1 year after surgery. The complete T2DM remission rate was 66.7% one year after surgery; the complete remitters had significantly lower FGF 19 levels and higher insulin levels than the non-complete remitters. The complete remitters also had significantly decreased total bile acid levels and increased FGF 19 levels 1 year after surgery compared with those before surgery. The fatty improvers had significantly decreased total bile acid levels and increased FGF 19 levels 1 year after surgery compared with those before surgery. Conclusion: The total bile acids level and fatty liver index decreased, and the FGF 19 levels increased 1 year after SG. Both T2DM complete remitters and NAFLD improvers showed significantly decreased total bile acid levels and increased FGF 19 levels 1 year after SG. Plasma total bile acids and FGF 19 might have roles in T2DM remission and NAFLD improvement. Low preoperative FGF 19 levels might be a predictor for NAFLD improvement after SG.

Bile acids and the metabolic syndrome

2019 ◽  
Vol 56 (3) ◽  
pp. 326-337 ◽  
Author(s):  
Emma Rose McGlone ◽  
Stephen R Bloom
Keyword(s):  
Diabetes Mellitus ◽  
Bile Acid ◽  
Bile Acids ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Metabolic Effects ◽  
Alcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
Alcoholic Fatty Liver Disease

Bile acids have important roles in the regulation of lipid, glucose and energy metabolism. Metabolic diseases linked to obesity, including type 2 diabetes mellitus and non-alcoholic fatty liver disease, are associated with dysregulation of bile acid homeostasis. Here, the basic chemistry and regulation of bile acids as well as their metabolic effects will be reviewed. Changes in circulating bile acids associated with obesity and related diseases will be reviewed. Finally, pharmaceutical manipulation of bile acid homeostasis as therapy for metabolic diseases will be outlined.

310 Bile Acid Diarrhea Is Associated With Non-Alcoholic Fatty Liver Disease

2015 ◽  
Vol 148 (4) ◽  
pp. S-68-S-69
Author(s):  
Richard N. Appleby ◽  
Jonathan D. Nolan ◽  
Ian M. Johnston ◽  
Sanjeev S. Pattni ◽  
Jessica M. Fox ◽  
...  
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

scholarly journals Aryl Hydrocarbon Receptor (AhR) Activation by 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) Dose-Dependently Shifts the Gut Microbiome Consistent with the Progression of Non-Alcoholic Fatty Liver Disease

2021 ◽  
Vol 22 (22) ◽  
pp. 12431
Author(s):  
Russell R. Fling ◽  
Timothy R. Zacharewski
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Fatty Liver ◽  
Bile Acids ◽  
Fatty Liver Disease ◽  
Acid Metabolism ◽  
Bile Acid Metabolism ◽  
Alcoholic Fatty Liver ◽  
Dose Dependent ◽  
Alcoholic Fatty Liver Disease

Gut dysbiosis with disrupted enterohepatic bile acid metabolism is commonly associated with non-alcoholic fatty liver disease (NAFLD) and recapitulated in a NAFLD-phenotype elicited by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice. TCDD induces hepatic fat accumulation and increases levels of secondary bile acids, including taurolithocholic acid and deoxycholic acid (microbial modified bile acids involved in host bile acid regulation signaling pathways). To investigate the effects of TCDD on the gut microbiota, the cecum contents of male C57BL/6 mice orally gavaged with sesame oil vehicle or 0.3, 3, or 30 µg/kg TCDD were examined using shotgun metagenomic sequencing. Taxonomic analysis identified dose-dependent increases in Lactobacillus species (i.e., Lactobacillus reuteri). Increased species were also associated with dose-dependent increases in bile salt hydrolase sequences, responsible for deconjugation reactions in secondary bile acid metabolism. Increased L. reuteri levels were further associated with mevalonate-dependent isopentenyl diphosphate (IPP) biosynthesis and o-succinylbenzoate synthase, a menaquinone biosynthesis associated gene. Analysis of the gut microbiomes from cirrhosis patients identified an increased abundance of genes from the mevalonate-dependent IPP biosynthesis as well as several other menaquinone biosynthesis genes, including o-succinylbenzoate synthase. These results extend the association of lactobacilli with the AhR/intestinal axis in NAFLD progression and highlight the similarities between TCDD-elicited phenotypes in mice to human NAFLD.

Sign in / Sign up

Export Citation Format

Share Document