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Abstract
Primary liver cancer (PLC), which includes intrahepatic cholangiocarcinoma (iCCA) and hepatocellular carcinoma (HCC), has the highest incidence of all cancer types in Thailand. Known etiological factors, such as viral hepatitis and chronic liver disease do not fully account for the country’s unusually high incidence. However, the gut-liver axis, which contributes to carcinogenesis and disease progression, is influenced by the gut microbiome. To investigate this relationship, fecal matter from 44 Thai PLC patients and 76 healthy controls were subjected to whole-genome metagenomic shotgun sequencing and then analyzed by marker gene-based and assembly based methods. Results revealed greater gut microbiome heterogeneity in iCCA compared to HCC and healthy controls. Two Veillonella species were found to be more abundant in iCCA samples and could distinguish iCCA from HCC and healthy controls. Conversely, Ruminococcus gnavus was depleted in iCCA patients and could distinguish HCC from iCCA samples. High Veillonella genus counts in the iCCA group were associated with enriched amino acid biosynthesis and glycolysis pathways, while enriched phospholipid and thiamine metabolism pathways characterized the HCC group with high Blautia genus counts. These findings reveal distinct landscapes of gut dysbiosis among Thai iCCA and HCC patients and warrant further investigation as potential biomarkers.
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1 Chulabhorn Research Institute, Translational Research Unit, Bangkok, Thailand (GRID:grid.418595.4) (ISNI:0000 0004 0617 2559)
2 Chulabhorn Research Institute, Laboratory of Chemical Carcinogenesis, Bangkok, Thailand (GRID:grid.418595.4) (ISNI:0000 0004 0617 2559); Center of Excellence on Environmental Health and Toxicology (EHT), OPS, MHESI, Bangkok, Thailand (GRID:grid.10223.32) (ISNI:0000 0004 1937 0490)
3 Chulabhorn Research Institute, Laboratory of Chemical Carcinogenesis, Bangkok, Thailand (GRID:grid.418595.4) (ISNI:0000 0004 0617 2559)
4 National Cancer Institute, Liver Cancer Program, Center for Cancer Research, Bethesda, USA (GRID:grid.48336.3a) (ISNI:0000 0004 1936 8075); National Cancer Institute, Laboratory of Human Carcinogenesis, Center for Cancer Research, Bethesda, USA (GRID:grid.48336.3a) (ISNI:0000 0004 1936 8075)
5 Chulabhorn Research Institute, Laboratory of Chemical Carcinogenesis, Bangkok, Thailand (GRID:grid.418595.4) (ISNI:0000 0004 0617 2559); Khon Kaen University, Faculty of Medicine, Khon Kaen, Thailand (GRID:grid.9786.0) (ISNI:0000 0004 0470 0856)
6 Chiang Mai University, Faculty of Medicine, Chiang Mai, Thailand (GRID:grid.7132.7) (ISNI:0000 0000 9039 7662)
7 Khon Kaen University, Faculty of Medicine, Khon Kaen, Thailand (GRID:grid.9786.0) (ISNI:0000 0004 0470 0856)
8 Chulabhorn Royal Academy, Princess Srisavangavadhana College of Medicine, Bangkok, Thailand (GRID:grid.512982.5) (ISNI:0000 0004 7598 2416)
9 Chulabhorn Royal Academy, Chulabhorn Hospital, Bangkok, Thailand (GRID:grid.512982.5) (ISNI:0000 0004 7598 2416)
10 Rajavej Hospital, Chiang Mai, Thailand (GRID:grid.512982.5)
11 National Cancer Institute, Bangkok, Thailand (GRID:grid.419173.9) (ISNI:0000 0000 9607 5779)
12 Georgetown University Medical Center, Washington, USA (GRID:grid.411667.3) (ISNI:0000 0001 2186 0438)
13 National Cancer Institute, Laboratory of Human Carcinogenesis, Center for Cancer Research, Bethesda, USA (GRID:grid.48336.3a) (ISNI:0000 0004 1936 8075)
14 National Cancer Institute, Liver Cancer Program, Center for Cancer Research, Bethesda, USA (GRID:grid.48336.3a) (ISNI:0000 0004 1936 8075); National Cancer Institute, Laboratory of Human Carcinogenesis, Center for Cancer Research, Bethesda, USA (GRID:grid.48336.3a) (ISNI:0000 0004 1936 8075); National Cancer Institute, Laboratory of Human Carcinogenesis, Center for Cancer Research, Bethesda, USA (GRID:grid.48336.3a) (ISNI:0000 0004 1936 8075)