Gut Microbiome Signatures Differ in Cirrhosis With and Without Hepatocellular Carcinoma in a Southeast Asian Cohort

Gut microbiota, microbial metabolites, and inflammatory cytokines play key roles in the pathogenesis of cirrhosis and hepatocellular carcinoma (HCC); however, data from Southeast Asia are limited. This study examined microbial composition, intestinal permeability, butyrate-related gene expression, and cytokine profiles in Thai patients with cirrhosis, with and without HCC.

This cross-sectional study included 30 healthy controls, 33 patients with cirrhosis without HCC, and 44 patients with HCC (HCC-cirr). Fecal samples were analyzed using 16S rRNA sequencing. Microbial functional profiles were predicted using KEGG Orthology-based pathway inference. Gut permeability markers (intestinal fatty acid-binding protein [I-FABP] and lipopolysaccharide-binding protein [LBP]), butyrate-associated gene (BCoAT) expression, and cytokine profiles were assessed.

Alpha diversity (Chao1) was significantly lower in HCC-cirr patients than in healthy controls (p < 0.001) and patients with cirrhosis (p = 0.008). Beta diversity also differed significantly between HCC-cirr and controls (p = 0.008). Ligilactobacillus, Catenibacterium, and Alloprevotella were enriched in the cirrhosis group, whereas HCC-cirr patients showed increased Ruminococcus gnavus and reduced butyrate producers (Coprococcus, Subdoligranulum). Functional prediction suggested pathway differences between cirrhosis and HCC-cirr, including folate, sulfur, tyrosine metabolism, and steroid biosynthesis. BCoAT expression was significantly decreased in HCC (p = 0.006). Plasma LBP and I-FABP were significantly elevated in HCC-cirr (p = 0.033, p < 0.001), with I-FABP also higher than in cirrhosis (p = 0.002). Proinflammatory cytokines (GM-CSF, IL-10, IL-18, IL-1α, IL-7, IL-8, and M-CSF) were elevated in HCC-cirr.

Among the Thai cohort, HCC with cirrhosis was associated with distinct gut microbial changes, reduced BCoAT expression, increased gut permeability, and cytokine alterations, highlighting the contribution of gut dysbiosis and microbial by-products to liver disease progression.