Gut microbiota and host transcriptome interactions reveal diagnostic biomarkers in MASLD-associated hepatocellular carcinoma.

BACKGROUND

Alterations in the gut microbiome via the gut-liver axis are closely linked to metabolic dysfunction-associated steatotic liver disease (MASLD) and may contribute to hepatocellular carcinoma (HCC) development. However, the interplay between the gut microbiome and host gene expression in MASLD and HCC remains poorly understood.

METHODS

We analyzed the gut microbiome from fecal samples and host transcriptomic profiles from peripheral blood mononuclear cells (PBMCs) in healthy controls and MASLD patients without HCC (mild fibrosis F01 and significant fibrosis F234) and with HCC.

RESULTS

Integrated analysis identified 260 differentially expressed genes (DEGs) and 29 bacterial taxa differentiating MASLD without HCC from MASLD-HCC. Subgroup analysis revealed seven bacterial genera associated with 84 host genes. Notably, Veillonella correlated with regulating synaptic membrane exocytosis 3 (RIMS3), collagen type X alpha 1 (COL10A1), and enabled homolog (ENAH). Real-time PCR validation confirmed COL10A1 as a significant diagnostic biomarker for distinguishing MASLD from MASLD-HCC (AUC = 0.835). Combining COL10A1, and AFP, or Veillonella with AFP, significantly improved differentiation between MASLD and MASLD-HCC, particularly in early-stage fibrosis (F01) (AUC = 0.941 and 0.996, respectively).

CONCLUSIONS

Gut microbiome-host gene interactions appear to play a significant role in MASLD-related HCC progression. Specific bacterial genera and host gene expression profiles may serve as early diagnostic markers for MASLD-HCC.