Landscapes of gut microbiome and bile acid signatures and their interaction in HBV-associated acute-on-chronic liver failure

IntroductionSubmassive hepatic necrosis (SMHN, defined as necrosis of 15–90% of the entire liver on explant) is a likely characteristic pathological feature of ACLF in patients with hepatitis B cirrhosis. We aimed to comprehensively explore microbiome and bile acids patterns across enterhepatic circ...

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Main Authors: Zhiwei Bao, Runan Wei, Xiaoping Zheng, Ting Zhang, Yunjiao Bi, Sijia Shen, Pengfei Zou, Junjie Zhang, Huadong Yan, Ming D. Li, Zhongli Yang, Hainv Gao
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-05-01
Series:Frontiers in Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2023.1185993/full
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author Zhiwei Bao
Runan Wei
Xiaoping Zheng
Ting Zhang
Yunjiao Bi
Sijia Shen
Pengfei Zou
Junjie Zhang
Huadong Yan
Ming D. Li
Ming D. Li
Zhongli Yang
Hainv Gao
author_facet Zhiwei Bao
Runan Wei
Xiaoping Zheng
Ting Zhang
Yunjiao Bi
Sijia Shen
Pengfei Zou
Junjie Zhang
Huadong Yan
Ming D. Li
Ming D. Li
Zhongli Yang
Hainv Gao
author_sort Zhiwei Bao
collection DOAJ
description IntroductionSubmassive hepatic necrosis (SMHN, defined as necrosis of 15–90% of the entire liver on explant) is a likely characteristic pathological feature of ACLF in patients with hepatitis B cirrhosis. We aimed to comprehensively explore microbiome and bile acids patterns across enterhepatic circulation and build well-performing machine learning models to predict SMHN status.MethodsBased on the presence or absence of SMHN, 17 patients with HBV-related end-stage liver disease who received liver transplantation were eligible for inclusion. Serum, portal venous blood, and stool samples were collected for comparing differences of BA spectra and gut microbiome and their interactions. We adopted the random forest algorithm with recursive feature elimination (RF-RFE) to predict SMHN status.ResultsBy comparing total BA spectrum between SMHN (−) and SMHN (+) patients, significant changes were detected only in fecal (P = 0.015). Compared with the SMHN (+) group, the SMHN (−) group showed that UDCA, 7-KLCA, 3-DHCA, 7-KDCA, ISOLCA and α-MCA in feces, r-MCA, 7-KLCA and 7-KDCA in serum, γ-MCA and 7-KLCA in portal vein were enriched, and TUDCA in feces was depleted. PCoA analysis showed significantly distinct overall microbial composition in two groups (P = 0.026). Co-abundance analysis showed that bacterial species formed strong and broad relationships with BAs. Among them, Parabacteroides distasonis had the highest node degree. We further identified a combinatorial marker panel with a high AUC of 0.92.DiscussionOur study demonstrated the changes and interactions of intestinal microbiome and BAs during enterohepatic circulation in ACLF patients with SMHN. In addition, we identified a combinatorial marker panel as non-invasive biomarkers to distinguish the SMHN status with high AUC.
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spelling doaj.art-baa8157a4e70428aa2cdd67e3b7665c32023-05-18T11:53:17ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2023-05-011410.3389/fmicb.2023.11859931185993Landscapes of gut microbiome and bile acid signatures and their interaction in HBV-associated acute-on-chronic liver failureZhiwei Bao0Runan Wei1Xiaoping Zheng2Ting Zhang3Yunjiao Bi4Sijia Shen5Pengfei Zou6Junjie Zhang7Huadong Yan8Ming D. Li9Ming D. Li10Zhongli Yang11Hainv Gao12State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Infectious Diseases, ShuLan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, ChinaDepartment of Infectious Diseases, ShuLan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, ChinaThe Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, ChinaState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Infectious Diseases, ShuLan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, ChinaThe Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Infectious Diseases, ShuLan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, ChinaState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaResearch Center for Air Pollution and Health, Zhejiang University, Hangzhou, ChinaState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Infectious Diseases, ShuLan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, ChinaIntroductionSubmassive hepatic necrosis (SMHN, defined as necrosis of 15–90% of the entire liver on explant) is a likely characteristic pathological feature of ACLF in patients with hepatitis B cirrhosis. We aimed to comprehensively explore microbiome and bile acids patterns across enterhepatic circulation and build well-performing machine learning models to predict SMHN status.MethodsBased on the presence or absence of SMHN, 17 patients with HBV-related end-stage liver disease who received liver transplantation were eligible for inclusion. Serum, portal venous blood, and stool samples were collected for comparing differences of BA spectra and gut microbiome and their interactions. We adopted the random forest algorithm with recursive feature elimination (RF-RFE) to predict SMHN status.ResultsBy comparing total BA spectrum between SMHN (−) and SMHN (+) patients, significant changes were detected only in fecal (P = 0.015). Compared with the SMHN (+) group, the SMHN (−) group showed that UDCA, 7-KLCA, 3-DHCA, 7-KDCA, ISOLCA and α-MCA in feces, r-MCA, 7-KLCA and 7-KDCA in serum, γ-MCA and 7-KLCA in portal vein were enriched, and TUDCA in feces was depleted. PCoA analysis showed significantly distinct overall microbial composition in two groups (P = 0.026). Co-abundance analysis showed that bacterial species formed strong and broad relationships with BAs. Among them, Parabacteroides distasonis had the highest node degree. We further identified a combinatorial marker panel with a high AUC of 0.92.DiscussionOur study demonstrated the changes and interactions of intestinal microbiome and BAs during enterohepatic circulation in ACLF patients with SMHN. In addition, we identified a combinatorial marker panel as non-invasive biomarkers to distinguish the SMHN status with high AUC.https://www.frontiersin.org/articles/10.3389/fmicb.2023.1185993/fullacute-on-chronic liver failuresubmassive hepatic necrosisacute decompensationbile acids (BAs)gut microbiome
spellingShingle Zhiwei Bao
Runan Wei
Xiaoping Zheng
Ting Zhang
Yunjiao Bi
Sijia Shen
Pengfei Zou
Junjie Zhang
Huadong Yan
Ming D. Li
Ming D. Li
Zhongli Yang
Hainv Gao
Landscapes of gut microbiome and bile acid signatures and their interaction in HBV-associated acute-on-chronic liver failure
Frontiers in Microbiology
acute-on-chronic liver failure
submassive hepatic necrosis
acute decompensation
bile acids (BAs)
gut microbiome
title Landscapes of gut microbiome and bile acid signatures and their interaction in HBV-associated acute-on-chronic liver failure
title_full Landscapes of gut microbiome and bile acid signatures and their interaction in HBV-associated acute-on-chronic liver failure
title_fullStr Landscapes of gut microbiome and bile acid signatures and their interaction in HBV-associated acute-on-chronic liver failure
title_full_unstemmed Landscapes of gut microbiome and bile acid signatures and their interaction in HBV-associated acute-on-chronic liver failure
title_short Landscapes of gut microbiome and bile acid signatures and their interaction in HBV-associated acute-on-chronic liver failure
title_sort landscapes of gut microbiome and bile acid signatures and their interaction in hbv associated acute on chronic liver failure
topic acute-on-chronic liver failure
submassive hepatic necrosis
acute decompensation
bile acids (BAs)
gut microbiome
url https://www.frontiersin.org/articles/10.3389/fmicb.2023.1185993/full
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