Observational Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 14, 2023; 29(22): 3534-3547
Published online Jun 14, 2023. doi: 10.3748/wjg.v29.i22.3534
Difference and clinical value of metabolites in plasma and feces of patients with alcohol-related liver cirrhosis
Yi-Fan Xu, Yan-Xu Hao, Lei Ma, Meng-Han Zhang, Xuan-Xuan Niu, Yan Li, Yuan-Yuan Zhang, Ting-Ting Liu, Ming Han, Xiao-Xue Yuan, Gang Wan, Hui-Chun Xing
Yi-Fan Xu, Yan-Xu Hao, Lei Ma, Meng-Han Zhang, Xuan-Xuan Niu, Yan Li, Hui-Chun Xing, Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
Yuan-Yuan Zhang, Ting-Ting Liu, Ming Han, Xiao-Xue Yuan, Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
Yuan-Yuan Zhang, Ting-Ting Liu, Ming Han, Xiao-Xue Yuan, Beijing Institute of Infectious Diseases, Beijing Institute of Infectious Diseases, Beijing 100015, China
Yuan-Yuan Zhang, Ting-Ting Liu, Ming Han, Xiao-Xue Yuan, National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
Gang Wan, Department of Statistic, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
Hui-Chun Xing, Center of Liver Diseases Division 3, Beijing Ditan Hospital, Peking University Ditan Teaching Hospital, Beijing 100015, China
Author contributions: Xing HC had designed the article; Xu YF, Hao YX, Ma L, Zhang MH, Niu XX, and Li Y had enrolled patients and collected data; Han M and Yuan XX had collected samples; Zhang YY, Liu TT, Xu YF, and Wan G had analyzed the data; Xu YF had drafted the manuscript; Xing HC had revised the manuscript for critical content.
Supported by National Key R&D Program of China, No. 21YFC2301801; and Capital's Funds for Health Improvement and Research of China, No. 2020-1-2171.
Institutional review board statement: This research scheme was reviewed and approved by the Ethics Committee of Ditan hospital (Beijing, China) and registered at http://www.chictr.org.cn/ (ChiCTR2000038216).
Informed consent statement: Written informed consent was obtained from all study participants or their legal guardian prior to study enrollment.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hui-Chun Xing, Doctor, MD, Chief Doctor, Professor, Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital Medical University, No. 8 Jingshun East Street, Chaoyang District, Beijing 100015, China. huichunxing@126.com
Received: February 26, 2023
Peer-review started: February 26, 2023
First decision: March 10, 2023
Revised: March 15, 2023
Accepted: May 4, 2023
Article in press: May 4, 2023
Published online: June 14, 2023
Processing time: 100 Days and 15.3 Hours
ARTICLE HIGHLIGHTS
Research background

Alterations in plasma and intestinal metabolites contribute to the pathogenesis and progression of alcohol-related liver cirrhosis (ALC).

Research motivation

Metabolites in enterohepatic circulation play an important role in cross-talk between liver and gut. The metabolites in the blood or the feces may have homogeneity but may also have specific characteristics related to their respective environments. The correlation between intestinal and plasma metabolites in patients with ALC, which might be helpful for the diagnosis and treatment of ALC, has not yet been elucidated.

Research objectives

To explore the common and different metabolites in the plasma and feces of patients with ALC and evaluate their clinical implications.

Research methods

This was a case-controlled observation study. We prospectively enrolled two groups of subjects: individuals with ALC and healthy controls (HCs). We recruited age-matched healthy males as controls through recruitment advertisements. According to the inclusion and exclusion criteria, 27 patients with ALC and 24 HCs were selected. The plasma and feces samples were collected. Liver function, blood routine, and other indicators were detected with automatic biochemical and blood routine analyzers. Liquid chromatography-mass spectrometry was used to detect the plasma and feces metabolites. Also, the association of metabolites with clinical features was analyzed.

Research results

More than 8000 plasma and more than 10000 fecal metabolites of patients with ALC were detected. Among them, More than 300 metabolites were found both in the plasma and feces. Enrichment analysis showed that these common metabolites are enriched in bile and amino acid metabolic pathways. Moreover, patients with ALC had a higher level of glycocholic acid (GCA) and taurocholic acid (TCA) in plasma and a lower level of deoxycholic acid (DCA) in the feces, while L-threonine, L-phenylalanine, and L-tyrosine increased simultaneously in plasma and feces. These results was consistent with previous studies and have indeed confirmed the disorder of bile acid and amino acid metabolism in patients with ALC. Besides, GCA, TCA, L-methionine, L-phenylalanine, and L-tyrosine in plasma were positively correlated with total bilirubin (TBil), prothrombin time (PT), and maddrey discriminant function score (MDF) and negatively correlated with cholinesterase (CHE) and albumin (ALB). The DCA in feces was negatively correlated with TBil, MDF, and PT and positively correlated with CHE and ALB. AP/S BA ratio of plasma primary bile acid (GCA and TCA) to fecal secondary bile acid (DCA), which was relevant to TBil, PT, and MDF score was established, which may be used as a biomarker of the severity of ALC.

Research conclusions

Bile acid and amino acid metabolism play a very important role in the progression of ALC. The enrichment of GCA, TCA, L-phenylalanine, L-tyrosine, and L-methionine in the plasma of patients with ALC and the reduction of DCA in feces was related to the severity of ALC. The P/S BA ratio of plasma primary bile acids (GCA and TCA) to fecal secondary bile acid (DCA), was relevant to TBil, PT, and MDF score.

Research perspectives

Integrating intestinal microbiomics and metabolomics analysis is essential to decipher the molecular mechanisms underlying ALC. Since LC-MS analysis used in this study has limitations, further comparisons with other detection methods and complementary studies are required.