Association of gut microbiome and primary liver cancer: A two-sample Mendelian randomization and case-control study

Jun Ma; Jialiang Li; Chen Jin; Jinhuan Yang; Chongming Zheng; Kaiwen Chen; Yitong Xie; Yi Yang; Zhiyuan Bo; Jingxian Wang; Qing Su; Juejin Wang; Gang Chen; Yi Wang

doi:10.1111/liv.15466

Association of gut microbiome and primary liver cancer: A two-sample Mendelian randomization and case-control study

Liver Int. 2023 Jan;43(1):221-233. doi: 10.1111/liv.15466. Epub 2022 Nov 8.

Authors

Jun Ma¹, Jialiang Li², Chen Jin¹, Jinhuan Yang², Chongming Zheng², Kaiwen Chen², Yitong Xie², Yi Yang¹, Zhiyuan Bo², Jingxian Wang¹, Qing Su¹, Juejin Wang¹, Gang Chen^{2

3}, Yi Wang¹

Affiliations

¹ Department of Epidemiology and Biostatistics, School of Public Health and Management, Wenzhou Medical University, Wenzhou, China.
² Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
³ Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, China.

PMID: 36300678
DOI: 10.1111/liv.15466

Abstract

Background and aims: Observational epidemiology studies suggested a relationship between the gut microbiome and primary liver cancer. However, the causal relationship remains unclear because of confounding factors and reverse causality. We aimed to explore the causal role of the gut microbiome in the development of primary liver cancer, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).

Methods: Mendelian randomization (MR) study was conducted using summary statistics from genome-wide association studies (GWAS) of the gut microbiome and liver cancer, and sequencing data from a case-control study validated the findings. A 5-cohort GWAS study in Germany (N = 8956) served as exposure, whilst the UK biobank GWAS study (N = 456 348) served as an outcome. The case-control study was conducted at the First Affiliated Hospital of Wenzhou Medical University from December 2018 to October 2020 and included 184 HCC patients, 63 ICC patients and 40 healthy controls.

Results: A total of 57 features were available for MR analysis, and protective causal associations were identified for Family_Ruminococcaceae (OR = 0.46 [95% CI, 0.26-0.82]; p = .009) and Genus_Porphyromonadaceae (OR = 0.59 [95% CI, 0.42-0.83]; p = .003) with HCC, and for Family_Porphyromonadaceae (OR = 0.36 [95% CI, 0.14-0.94]; p = .036) and Genus_Bacteroidetes (OR = 0.55 [95% CI, 0.34-0.90]; p = .017) with ICC respectively. The case-control study results showed that the healthy controls had a higher relative abundance of Family_Ruminococcaceae (p = .00033), Family_Porphyromonadaceae (p = .0055) and Genus_Bacteroidetes (p = .021) than the liver cancer patients.

Conclusions: This study demonstrates that Ruminococcaceae, Porphyromonadaceae and Bacteroidetes are related to a reduced risk of liver cancer (HCC or ICC), suggesting potential significance for the prevention and control of liver cancer.

Keywords: Mendelian randomization; case-control study; gut microbiome; hepatocellular carcinoma; intrahepatic cholangiocarcinoma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bile Duct Neoplasms*
Bile Ducts, Intrahepatic
Carcinoma, Hepatocellular* / genetics
Case-Control Studies
Cholangiocarcinoma* / genetics
Gastrointestinal Microbiome* / genetics
Genome-Wide Association Study
Humans
Liver Neoplasms* / genetics
Mendelian Randomization Analysis
Polymorphism, Single Nucleotide

Abstract

Publication types

MeSH terms

Grants and funding