Distinct Gut Microbiota Profiles Associated with Advanced Hepatocellular Carcinoma in a Thai Cohort: A 16S rRNA Sequencing Study

<b>Background</b>: Hepatocellular carcinoma (HCC) remains a major contributor to global cancer mortality. Increasing evidence suggests that the gut microbiota is a key modulator of liver disease progression and a promising source of non-invasive biomarkers. However, regional disparities in microbial profiles, influenced by ethnicity, diet, and environment, limit the generalizability of the existing data. This study aimed to characterize gut microbiota alterations in Thai patients with advanced untreated HCC compared to healthy individuals. <b>Method</b>: Fecal samples from 27 untreated Thai advanced HCC patients were collected, and data from 31 healthy individuals retrieved from a previous study were employed. Gut microbiota profiles were analyzed using 16S rRNA gene sequencing. <b>Results</b>: Alpha diversity was significantly reduced in HCC patients (<i>p</i> < 0.001). At the phylum level, Proteobacteria and Firmicutes were enriched in HCC, whereas Actinobacteria were more abundant in controls. Proteobacteria and Bacteroidota levels were positively correlated with serum alpha-fetoprotein (AFP) levels, whereas Firmicutes were negatively correlated with ALBI scores. <b>Conclusions</b>: Thai patients with advanced HCC exhibited distinct gut microbial signatures, characterized by dysbiosis and expansion of Proteobacteria. These findings support the role of the gut microbiota as a potential non-invasive biomarker for disease severity and prognosis in HCC, underscoring the importance of population-specific microbial studies.