Dataset Information

Serum metabolome alterations in patients with early nonalcoholic fatty liver disease.

ABSTRACT:

Background

Although metabolomic analysis for patients with nonalcoholic fatty liver disease (NAFLD) was a promising approach to identify novel biomarkers as targets for the diagnosis of NAFLD, the serum metabolomics profile of early-stage NAFLD patients from central China remain unknown.

Objective

The aim of the present study was to explore the metabolic characteristics of patients with early-stage NAFLD based on the ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technology, to identify differential metabolites and perform functional analysis, and especially, to establish a novel early NAFLD clinical diagnostic tool.

Results

Compared with healthy controls, serum metabolite species increased significantly in early stage NAFLD patients. Expression of 88 metabolites including 1-naphthylmethanol, rosavin, and theophylline were up-regulated in early NAFLD, while 68 metabolites including 2-hydroxyphenylacetic acid and lysophosphatidylcholine (24:1(15Z)) were down-regulated. The early NAFLD classifier achieved a strong diagnostic efficiency in the discovery phases (80.99%) and was successfully verified in the validation phases (75.23%).

Conclusions

These results advance our understanding about the composition and biological functions of serum metabolites of early NAFLD. In addition, serum metabolic markers can serve as an efficient diagnostic tool for the early-stage NAFLD.

SUBMITTER: Wang X

PROVIDER: S-EPMC9583763 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

Serum metabolome alterations in patients with early nonalcoholic fatty liver disease.

Wang Xuemei X Rao Benchen B Wang Haiyu H Liu Chao C Ren Zhigang Z Yu Zujiang Z

Bioscience reports 20221001 10

<h4>Background</h4>Although metabolomic analysis for patients with nonalcoholic fatty liver disease (NAFLD) was a promising approach to identify novel biomarkers as targets for the diagnosis of NAFLD, the serum metabolomics profile of early-stage NAFLD patients from central China remain unknown.<h4>Objective</h4>The aim of the present study was to explore the metabolic characteristics of patients with early-stage NAFLD based on the ultra-performance liquid chromatography-tandem mass spectrometry ...[more]

PMID: 36124945

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Project description:Background & aimsSeries studies have associated increased serum levels of ferritin with liver fibrosis in patients with nonalcoholic fatty liver disease. We aimed to determine the accuracy with which measurements of serum ferritin determine the presence and severity of liver fibrosis, and whether combining noninvasive scoring systems with serum ferritin analysis increases the accuracy of diagnosis of advanced liver fibrosis.MethodsWe performed a retrospective analysis of data from 1014 patients with liver biopsy-confirmed nonalcoholic fatty liver disease. Three cut points of serum ferritin level, adjusted for sex, were established based on receiver operating characteristic curve analysis: 1.0-, 1.5-, and 2.0-fold the upper limit of normal. Three multiple logistic regression models were created to determine the association of these cutoff values with liver fibrosis, adjusting for age, sex, race, diabetes, body mass index, and level of alanine aminotransferase.ResultsA greater proportion of patients with increased serum levels of ferritin had definitive nonalcoholic steatohepatitis and more-advanced fibrosis than patients without increased levels. In all models, serum level of ferritin was significantly associated with the presence and severity of liver fibrosis. However, for all 3 cutoff values, area under the receiver operating characteristic curve values were low (less than 0.60) for the presence of fibrosis or any stage of liver fibrosis; ferritin level identified patients with fibrosis with 16%-41% sensitivity and 70%-92% specificity. The accuracy with which noninvasive scoring systems identified patients with advanced fibrosis did not change with inclusion of serum ferritin values.ConclusionsAlthough serum levels of ferritin correlate with more-severe liver fibrosis, based on adjusted multiple logistic regression analysis, serum ferritin levels alone have a low level of diagnostic accuracy for the presence or severity of liver fibrosis in patients with nonalcoholic fatty liver disease.

Project description:Rationale: Patients suffering from coronary artery disease (CAD) complicated with nonalcoholic fatty liver disease (NAFLD) present worse cardiovascular outcomes than CAD patients without NAFLD. The progression of CAD is recently reported to be associated with gut microbiota and microbe-derived metabolites. However, it remains unclear how the complication of NAFLD will affect gut microbiota and microbe-derived metabolites in CAD patients, and whether or not this interplay is related to the worse cardiovascular outcomes in CAD-NAFLD patients. Methods: We performed 16S rRNA sequencing and serum metabolomic analysis in 27 CAD patients with NAFLD, 81 CAD patients without NAFLD, and 24 matched healthy volunteers. Predicted functional profiling was achieved using PICRUSt2. The occurrence of cardiovascular events was assessed by a follow-up study. The association of alterations in the gut microbiome and metabolome with adverse cardiovascular events and clinical indicators was revealed by Spearman correlation analysis. Results: We discovered that the complication of NAFLD was associated with worse clinical outcomes in CAD patients and critical serum metabolome shifts. We identified 25 metabolite modules that were correlated with poor clinical outcome in CAD-NAFLD patients compared with non-NAFLD patients, represented by increased cardiac-toxic metabolites including prochloraz, brofaromine, aristolochic acid, triethanolamine, and reduced potentially beneficial metabolites including estradiol, chitotriose, palmitelaidic acid, and moxisylyte. In addition, the gut microbiome of individuals with CAD-NAFLD was changed and characterized by increased abundances of Oscillibacter ruminantium and Dialister invisus, and decreased abundances of Fusicatenibacter saccharivorans, Bacteroides ovatus and Prevotella copri. PICRUSt2 further confirmed an increase of potential pathogenic bacteria in CAD-NAFLD. Moreover, we found that variations of gut microbiota were critically correlated with changed circulating metabolites and clinical outcomes, which revealed that aberrant gut microbiota in CAD-NAFLD patients may sculpt a detrimental metabolome which results in adverse cardiovascular outcomes. Conclusions: Our findings suggest that CAD patients complicated with NAFLD result in worse clinical outcomes possibly by modulating the features of the gut microbiota and circulating metabolites. We introduce "liver-gut microbiota-heart axis" as a possible mechanism underlying this interrelationship. Our study provides new insights on the contribution of gut microbiota heterogeneity to CAD-NAFLD progression and suggests novel strategies for disease therapy.

Dataset Information

Serum metabolome alterations in patients with early nonalcoholic fatty liver disease.

Background

Objective

Results

Conclusions

Publications

Serum metabolome alterations in patients with early nonalcoholic fatty liver disease.

Similar Datasets

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