AUTHOR=Bao Zhiwei , Wei Runan , Zheng Xiaoping , Zhang Ting , Bi Yunjiao , Shen Sijia , Zou Pengfei , Zhang Junjie , Yan Huadong , Li Ming D. , Yang Zhongli , Gao Hainv TITLE=Landscapes of gut microbiome and bile acid signatures and their interaction in HBV-associated acute-on-chronic liver failure JOURNAL=Frontiers in Microbiology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1185993 DOI=10.3389/fmicb.2023.1185993 ISSN=1664-302X 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.