Pathway-Based Integrative Analysis of Metabolome and Microbiome Data from Hepatocellular Carcinoma and Liver Cirrhosis Patients

SIMPLE SUMMARY: Hepatocellular carcinoma (HCC) is one of the diseases associated with human microbiome. The human microbiome is known to affect human disease through the metabolites. The aim of this study was to identify the pathways associated with HCC by integrating microbiome and metabolomic data via a novel pathway-based integrative method named HisCoM-MnM representing Hierarchical structural Component Model for pathway analysis of Microbiome and Metabolome. Application of HisCoM-MnM to datasets from HCC and liver cirrhosis (LC) patients successfully identified HCC-related pathways related to cancer metabolic reprogramming along with the significant metabolome and metagenome that make up those pathways. ABSTRACT: Aberrations of the human microbiome are associated with diverse liver diseases, including hepatocellular carcinoma (HCC). Even if we can associate specific microbes with particular diseases, it is difficult to know mechanistically how the microbe contributes to the pathophysiology. Here, we sought to reveal the functional potential of the HCC-associated microbiome with the human metabolome which is known to play a role in connecting host phenotype to microbiome function. To utilize both microbiome and metabolomic data sets, we propose an innovative, pathway-based analysis, Hierarchical structural Component Model for pathway analysis of Microbiome and Metabolome (HisCoM-MnM), for integrating microbiome and metabolomic data. In particular, we used pathway information to integrate these two omics data sets, thus providing insight into biological interactions between different biological layers, with regard to the host’s phenotype. The application of HisCoM-MnM to data sets from 103 and 97 patients with HCC and liver cirrhosis (LC), respectively, showed that this approach could identify HCC-related pathways related to cancer metabolic reprogramming, in addition to the significant metabolome and metagenome that make up those pathways.