• Identifying contamination
• Prognostic power
What is already known on this topic
Determining the composition of the microbial communities inhabiting internal organs and whether these microbes are associated with diseases such as cancer remains challenging due to the difficulty of removing pieces of tissues from the body. What’s more, studies that analyze the microbiota of samples with a low prevalence of bacteia suffer from contamination during sample collection and DNA extraction.
What this research adds
By analyzing the prevalence of microbial species across samples from The Cancer Genome Atlas, researchers have created The Cancer Microbiome Atlas, a public database that contains information about the microbes residing in gastrointestinal cancer tissues. The analysis revealed that species found across different sample types are mostly contaminants, and that removing such species helped to isolate the tissue-resident bacteria. The database allowed the discovery of microbial species that are prognostic of specific gastrointestinal cancers as well as blood signatures of mucosal barrier injuries.
The Cancer Microbiome Atlas could help to explore the role of tissue-resident microbiota in various cancers and identify microbial biomarkers that are predictive of disease.
Determining the composition of the microbial communities inhabiting internal organs and whether these microbes are associated with diseases such as cancer remains challenging due to the difficulty of removing pieces of tissues from the body. What’s more, studies that analyze the microbiota of samples with a low prevalence of microbes suffer from contamination during sample collection and DNA extraction. Now, a new database that contains information about the microbes residing in gastrointestinal cancer tissues could help to distinguish resident microbes from contaminants.
The repository, dubbed The Cancer Microbiome Atlas, allowed the discovery of microbial species that are prognostic of specific gastrointestinal cancers as well as blood signatures of mucosal barrier injuries. The information contained in the database “will help guide future studies of the microbiome’s role in human health and disease,” the researchers say. The team detailed their findings in Cell Host & Microbe.
The Cancer Genome Atlas (TCGA) contains genomic data from hundreds of cancers and matched normal tissues. “Sequencing data in TCGA provide a unique opportunity for identifying tissue-specific microbiota, since matched tissue and blood samples from various cancer types are processed and sequenced in parallel using various sequencing platforms at designated centers,” the researchers say.
The team, led by Anders Dohlman and Xiling Shen at Duke University, used a statistical model that compares the prevalence of microbial species in tissue and blood samples, which allowed the isolation of tissue-resident microbiota in samples from nearly 2,000 cancer patients.
To study the microbial populations of TCGA tissues, the researchers analyzed sequencing data for 730 tissue and 555 blood samples from 617 people with colorectal cancer and for 958 tissue and 914 blood samples from 923 people with brain cancer.
Colorectal cancer tissues had a more abundant and diverse microbiota than brain cancer tissues, which is in line with the idea that brain tissue is more sterile than colorectal tissue. The researchers found two distinct groups of bacterial species in colorectal cancer tissues and blood samples: those enriched in tissues and those found in equal amounts in tissue and blood.
Further experiments showed that microbial species found across different tissue types and blood samples are mostly contaminants and are associated with particular sequencing centers.
Based on the analyses of microbial prevalence in tissue and blood, the researchers developed a statistical model that allowed them to distinguish tissue-resident microbiota from contaminant species across different cancer types. Of the 1,136 bacterial species found in more than 5% of colorectal cancer tissue samples, the model classified nearly 68% as tissue-resident and about 32% as contaminants.
Proteobacteria and Actinobacteria were the most common contaminants, whereas Fusobacterium and Bacteroides were commonly found in colorectal cancer tissue samples. Overall, about half of tumor-associated species belonged to the genus Fusobacterium, including F. nucleatum, which is known to promote intestinal tumor formation.
Bacteroides and Parabacteroides species were substantially more abundant in normal tissues than in matched cancer tissues, and more than a dozen Bacteroides species were prognostic of survival. Finally, the team found that the presence of specific microbes in colorectal cancer blood samples indicates mucosal barrier injury, which is a common feature of colorectal cancer and other long-term inflammatory conditions.
The Cancer Microbiome Atlas, the researchers conclude, “represents an unprecedented resource for exploring the role of tissue-resident microbiota in various cancer types and identifying predictive microbial biomarkers.”