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In Extensive Sequencing Study, Scientists Find Few Links Between Cancer and Microbiome

Aug, 4, 2025

Scientists at Johns Hopkins Medicine have reported findings that challenge earlier claims about the link between microbiomes and cancer. In a new study published Sept. 3 in Science Translational Medicine, researchers analyzed whole genome sequences from 5,734 tissue samples across 25 cancer types in The Cancer Genome Atlas (TCGA). Unlike previous studies they found far fewer microbial DNA sequences in the cancer tissues and no significant associations between microbiomes and most cancers. Steven Salzberg, Ph.D., Bloomberg Distinguished Professor at Johns Hopkins, emphasized that science evolves through validation and replication and these results provide a more complete picture of the microbiome–cancer connection.

The TCGA’s whole genome sequencing data generates millions of short DNA fragments, or reads from each tissue sample originally intended to help identify genetic mutations linked to cancer. However, these reads can also reveal microbial DNA present in tumors. A challenge arises because sequencing machines and laboratory environments can introduce contaminant DNA, making it difficult to distinguish genuine microbial signals from noise. To address this, Steven Salzberg notes that the team took extensive measures to filter out contaminants, ensuring the study’s findings were not distorted by false microbial associations.

To eliminate potential contaminants, Salzberg and his team applied their extensive genomic sequencing expertise and analyzed control samples to pinpoint reads likely originating from contamination. In this follow-up to their 2023 study, Salzberg and first author Yuchen Peter Ge, a Johns Hopkins biomedical engineering graduate student, filtered human DNA sequences from TCGA data by aligning each read against two reference genomes: the Telomere-to-Telomere (T2T) project genome and the Genome Reference Consortium genome.

In the current Johns Hopkins study the researchers detected microbiome DNA including microbes long associated with human cancers, such as HPV (linked to cervical and some head and neck cancers) Helicobacter pylori (stomach cancer) and Fusobacterium nucleatum and Bacteroides fragilis (gastrointestinal cancers). Both the current study and earlier ones in Cell and Nature reported Saccharomyces cerevisiae, or baker’s yeast a common sequencing lab contaminant. They also identified Rosellinia necatrix partitivirus 8, a virus that infects plant fungi and has no known connection to human disease. Salzberg notes that many previously reported microbial reads were likely due to such contaminants.

Source: https://www.hopkinsmedicine.org/news/newsroom/news-releases/2025/09/in-extensive-sequencing-study-scientists-find-few-links-between-cancer-and-microbiome


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