BACKGROUND: Nasopharyngeal carcinoma (NPC) is strongly associated with Epstein-Barr virus (EBV) infection. The gut microbiome can influence outcomes of viral infections but the potential links among the gut microbiome, EBV infection and NPC remain unclear. OBJECTIVE: To characterise gut microbiome alterations in EBV-associated NPC, evaluate microbiome-based diagnostic performance (alone and in combination with EBV markers), and explore associations between microbial features, EBV DNA burden, prognosis and the tumour microenvironment. DESIGN: We conducted a large-scale shotgun metagenomic study including 516 patients with EBV-associated NPC and 263 healthy controls. Microbiome dysbiosis, functional pathways and associations with plasma EBV DNA were assessed. Species-level markers were used to build a random forest classifier for NPC diagnosis, and performance was evaluated alone and in combination with EBV-specific markers. Survival analyses were performed to identify microbial features associated with NPC-related mortality and relationships with an immune-suppressive tumour microenvironment were explored. RESULTS: NPC was characterised by gut microbiome dysbiosis, including depletion of short-chain fatty acid-producing species and reduced butanoate metabolism, which were significantly associated with plasma EBV DNA. A random forest classifier based on species-level markers distinguished NPC from controls with an area under the curve (AUC) of 0.917; performance improved to an AUC of 0.984 when combined with EBV-specific markers. Specific microbial species were associated with NPC-related mortality and prognostic microbial features were linked to an immune-suppressive tumour microenvironment. CONCLUSION: EBV-associated NPC is associated with distinct gut microbiome and functional alterations that correlate with plasma EBV DNA. Microbial markers show strong diagnostic potential, particularly when integrated with EBV-specific markers, and prognostic microbial features may be linked to an immune-suppressive tumour microenvironment, supporting a potential role of the gut microbiome in NPC tumourigenesis.
Lan et al. (Tue,) studied this question.