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Known etiological factors, such as viral hepatitis and chronic liver disease do not fully account for the country\u2019s 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 <jats:italic>Veillonella<\/jats:italic> species were found to be more abundant in iCCA samples and could distinguish iCCA from HCC and healthy controls. Conversely, <jats:italic>Ruminococcus gnavus<\/jats:italic> was depleted in iCCA patients and could distinguish HCC from iCCA samples. High <jats:italic>Veillonella<\/jats:italic> 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 <jats:italic>Blautia<\/jats:italic> genus counts. 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