Integrated omics analysis: the relationship between significantly increased Klebsiella post-hepatectomy and decreased hub-metabolite 3-methyl-2-oxobutanoic acid is associated with induced liver failure

Yu-Chong Peng; Xin-Hua Zhao; Chuan-Fa Zeng; Jing-Xuan Xu; Lu-Nan Qi; Le-Qun Li

doi:10.21037/jgo-21-906

Integrated omics analysis: the relationship between significantly increased Klebsiella post-hepatectomy and decreased hub-metabolite 3-methyl-2-oxobutanoic acid is associated with induced liver failure

J Gastrointest Oncol. 2022 Feb;13(1):326-343. doi: 10.21037/jgo-21-906.

Authors

Yu-Chong Peng^#^{1

2}, Xin-Hua Zhao^#^{1

2}, Chuan-Fa Zeng^#^{1

2}, Jing-Xuan Xu^{1

2}, Lu-Nan Qi^{1

2}, Le-Qun Li^{1

2

3}

Affiliations

¹ Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China.
² Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of Education, Nanning, China.
³ Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, China.

^# Contributed equally.

Abstract

Background: This study sought to evaluate the association between intestinal Klebsiella and post-hepatectomy liver failure (PHLF) in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (B-HCC), and identify the inner relationship.

Methods: Patients with B-HCC were divided into Groups A and B based on the presence or absence of PHLF. 16S ribosomal ribonucleic acid surveys were used to identify gut microbiome alterations. PICRUST2 was used to examine the metagenomic data in PHLF patients. Fecal and serum samples were processed by chromatography-mass spectrometry based non-targeted metabonomics, then comprehensively analyzed to obtain hub metabolites. A Spearman correlation analysis was then conducted to find any associations between fecal differential metabolites and the relative abundance of differential microbes.

Results: Hepatectomies were significantly associated with a gut microbial imbalance in B-HCC patients, and a significant elevation of Klebsiella abundance was observed in PHLF patients. Klebsiella appears to act on 13 amino acid-related pathways, especially significantly observed in branched-chain amino acid (BCAA) metabolic pathways. Additionally, Klebsiella was found to be highly correlated with 3-methyl-2-oxobutanoic acid shared by feces and serum in the BCAA metabolic pathway.

Conclusions: Hepatectomy can lead to an imbalance of intestinal microflora in B-HCC patients. Due to its potential connections with 3-methyl-2-oxobutanoic acid in the BCAA pathway, significantly increased Klebsiella has the potential to be an evaluation indicator of PHLF in B-HCC patients. Moreover, 3-methyl-2-oxobutanoic acid has research value in PHLF-targeted treatments.

Keywords: 3-methyl-2-oxobutanoic acid; Hepatitis B virus-related hepatocellular carcinoma (hepatitis B-HCC); Klebsiella; gut microbiota; post-hepatectomy liver failure (PHLF).