The Microbiome–Cancer Genome Crosstalk

Over the past decade, the tumor microenvironment (TME) has been extensively studied through the lens of immune cell infiltration, stromal signaling, and cytokine networks. Direct tissue-based profiling has established the presence of low-biomass, tumor-type-associated bacterial communities in some cancers, reframing the tumor as an ecological system in which microbes can influence mutagenesis, immune evasion, and treatment response. At the same time, reanalyses of public sequencing repositories have shown that a substantial fraction of previously reported microbial signal reflects contamination and database artifacts, making rigorous methodology the precondition for mechanistic progress in this field. Against this backdrop, the mechanistic relationships between the intratumoral microbiome and cancer genome dynamics remain incompletely defined. Key unresolved questions include how bacterial metabolites and genotoxins contribute to DNA damage, how microbial communities shape the neoantigen landscape, whether microbiome-informed biomarkers could enhance patient stratification in precision oncology, and how causal microbial contributions to specific mutational signatures can be distinguished from mere association.This Research Topic aims to consolidate and advance current knowledge in this rapidly developing field by examining the molecular, genomic, and immunological mechanisms through which intratumoral bacteria influence tumor biology and evolution. The objective is to integrate insights from genomics, microbiology, immunology, and bioinformatics to identify causal pathways linking bacterial presence and activity to host genome instability, mutational signatures, and immune modulation. Submissions exploring both basic and translational dimensions are encouraged, including studies focusing on microbial metabolites, immune microenvironment interactions, and the clinical utility of microbiome-based biomarkers. Reviews, original research, perspectives, and methodological papers advancing the detection, characterization, and mechanistic understanding of the tumor microbiome are all welcome.To gather further insights into the intersection of cancer genetics and oncogenomics, we welcome articles addressing, but not limited to, the following themes:• Characterization of tumor-type-specific microbial profiles using metagenomics and spatial technologies• Mechanistic studies of bacterial genotoxins and their role in mutational imprinting and genome instability• Microbiome-driven modulation of host DNA damage response and replication fidelity• Bacterial influence on the tumor immune microenvironment, antigen presentation, and neoantigen and genomic consequences of microbial activity• Methodological rigor in low-biomass tumor microbiome analysis: contamination control, negative and environmental controls, database curation, batch-effect handling, and benchmarking of decontamination pipelines• Integration of metagenomic, transcriptomic, proteomic, and metabolomic data in microbiome–cancer analyses• Machine learning and computational approaches for microbiome–genome co-analysis and classification• Disentangling causation from association: experimental and computational approaches to establishing microbial contribution to specific mutational signatures• Clinical and translational applications of intratumoral microbiome profiling for biomarker discovery and therapy personalization• Ancestry-stratified host–microbiome interactions and population differences in mutational signature attribution Topic editors: Sahar Qazi, Abdullah Awadh Source: https://www.frontiersin.org/research-topics/82257/the-microbiome-cancer-genome-crosstalk