The new microbiome on the block: challenges and opportunities of using human tumor sequencing data to study microbes

Microbes within tumors have been recognized and experimentally related to oncogenesis, tumor growth, metastasis and therapeutic responsiveness. Studying the tumor microbiome presents difficulties, as early indications suggest that microbe populations are low in abundance, sparse and highly heterogeneous. Disparate results from computational profiling of the tumor microbiome have cast doubt on the premise of microbes in tumors. Yet decades of experimental evidence support the presence of tumor microbes, at least in a limited number of tumor types. In this Perspective, we discuss the importance of iteratively improving microbe-targeted sequencing techniques, established analytical pipelines, robust computational tools and solid validations to address current challenges and fill existing knowledge gaps. The vast amount of human tumor sequencing data available could greatly enhance systematic investigations of microbiome–tumor interactions with methods to quantify the composition of the tumor microbiome accurately. This Perspective explores the challenges and future directions in the world of human tumor microbiome research.