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

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

doi:10.3389/fmicb.2023.1185993

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

Front Microbiol. 2023 May 18:14:1185993. doi: 10.3389/fmicb.2023.1185993. eCollection 2023.

Authors

Zhiwei Bao^#¹, Runan Wei^#¹, Xiaoping Zheng^#², Ting Zhang², Yunjiao Bi³, Sijia Shen¹, Pengfei Zou², Junjie Zhang³, Huadong Yan², Ming D Li^{1

4}, Zhongli Yang¹, Hainv Gao²

Affiliations

¹ State 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, China.
² Department of Infectious Diseases, ShuLan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, China.
³ The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, China.
⁴ Research Center for Air Pollution and Health, Zhejiang University, Hangzhou, China.

^# Contributed equally.

Abstract

Introduction: Submassive 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.

Methods: Based 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.

Results: By 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.

Discussion: Our 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.

Keywords: acute decompensation; acute-on-chronic liver failure; bile acids (BAs); gut microbiome; submassive hepatic necrosis.

Grants and funding

This study was supported by the Chinese Nature Science Foundation (grant no. 81790634), the Zhejiang Non-public Medical Specialty Program, the National Key Research and Development Program of China (2021YFA1301104), and the Research Project of Jinan Microecological Biomedicine Shandong Laboratory.