Disentangling the molecular mystery of tumour-microbiota interactions: Microbial metabolites

The profound impact of the microbiota on the initiation and progression of cancer has been a focus of attention. In recent years, many studies have shown that microbial metabolites serve as key hubs that connect the microbiome and cancer progression, but the underlying molecular mechanisms have not been fully elucidated. Multiple mechanisms that influence tumour development and therapy resistance, including disrupting cellular signalling pathways, triggering oxidative stress, inducing metabolic reprogramming and reshaping tumour immune microenvironment, are reviewed. Focusing on recent advancements in this field, this review also summarises the methodological framework of studies regarding microbial metabolites. In this review, we outline the current state of research on tumour-associated microbial metabolites and describe the challenges in future scientific research and clinical applications. KEY POINTS: Metabolites derived from both gut and intratumoural microbiota play important roles in cancer initiation and progression. The dual roles of microbial metabolites pose an obstacle for clinical translations. Absolute quantification and tracing techniques of microbial metabolites are essential for addressing the gaps in studies on microbial metabolites. Integrating microbial metabolomics with multi-omics transcends current research paradigms.