Meta-analysis of approximately 6,800 gut microbiome profiles reveals microbial signatures associated with colorectal cancer. This finding forms the basis for future use of microbiome-based tools to assess cancer risk and prevention, although this is not yet a diagnostic test.
This was discovered after combining data from 27 studies, including researchers from the Mi-EOCRC consortium across Germany, Switzerland and the Netherlands, and the Zeller and Zimmermann groups at the European Molecular Biology Laboratory (EMBL) Heidelberg.
Using machine learning algorithms to detect cancerous microbiomes from non-cancerous microbiomes, the research team found consistent patterns in the cancer microbiome across different populations. Notably, the researchers linked the variation to dietary fiber intake.
According to the researchers, microbiome signatures of colorectal cancer are detectable in early-stage tumors but less so in precancerous adenomas.
overcome previous challenges
The researchers said: Cell hosts and microorganisms This study is one of the most comprehensive analyzes to date of the gut microbiota associated with colorectal cancer.
Previous literature has reported that the microbiomes of people with and without colorectal cancer are different. However, many of these studies are small and use different sequencing methods, making it difficult to know which microbial changes are reproducible, as other meta-analyses have noted.
The study combined data from 27 studies in Germany, Switzerland, and the Netherlands.Commenting on how the new study addresses previous challenges, Georg Zeller, visiting team leader at EMBL Heidelberg, said: “The strength of this study is its comprehensiveness. We combined stool and tissue comparisons, dietary data, taxonomic analysis down to bacterial strains, and functional analysis of virulence factors.”
His team analyzed data from 6,779 publicly available gut microbiome sequence profiles and 906 intestinal tissue samples. This was used to compare the stool-based microbiome signal with the signal found in tumor tissue.
New research has made methodological advances using computational approaches that integrate datasets from different sequencing techniques at scale.
“An important tool is a machine learning algorithm trained to distinguish between cancer and non-cancer microbiomes,” said Zeller, who is also a professor at Leiden University Medical Center in the Netherlands. “This outputs a score of how ‘cancer-like’ the microbiome is. This can be applied to existing human gut microbiome datasets, such as dietary intervention studies.”
An integrated approach means that microbiome characteristics are not limited and can be applied to the entire population.
Additionally, the researchers suggest that their tool could help build future machine learning for risk assessment, early detection, and personalized prevention research. However, larger-scale testing is needed to know whether microbiome data can complement or be combined with current clinical testing.
Detecting issues
The study found that microorganisms in tumor tissue resembled characteristics of colorectal cancer in fecal samples.
Cancer-associated microorganisms were already detectable at an early stage in tissue samples. However, detection rates were low in the early stages in stool samples and tumor locations above the colon. The researchers explain that this may be because the tumor-derived microorganisms are smaller or farther from the rectum.
“These results suggest that microbiome changes associated with colorectal cancer may appear early in the development of the disease and raise questions about how tumors shape their microbiomes and how microorganisms influence the tumor microenvironment through signaling, metabolism, and other interactions,” commented Michael Zimmermann, group leader at EMBL Heidelberg.
F. nucleatum subspecies animal Consistently detected in colorectal cancer samples from multiple continents.Another limitation was that the detection of microbial changes associated with adenoma was weaker than that of colorectal cancer.
“This limitation is important for the future clinical translation that the Mi-EOCRC consortium is aiming for,” adds Zimmermann. “Our findings suggest that more sensitive approaches, larger datasets, or combinations with other measurements may be required for microbiome-based tools to contribute to the reliable detection of early precancerous lesions.”
How diet and fiber affect disease
The research team found that lower dietary fiber intake was strongly associated with cancer-related microbiome patterns. The reverse is also noted, as diets high in fiber intake are associated with lower microbiome signature scores for colorectal cancer.
Therefore, they note that diet and fiber can influence microbial patterns associated with colorectal cancer, and show that gut bacteria are associated with cancer risk, progression, or prevention.
Additionally, the researchers highlight that machine learning scores can be applied to existing microbiome databases, such as dietary intervention studies, which can help researchers better understand the influence of lifestyle on disease-related microbiome patterns.
Experts have previously advocated for the industry to innovate plant-based, high-fiber solutions to address the rising incidence of colon cancer, as many consumers have misconceptions about the link between diet and colon cancer.
Association between bacterial enrichment and colorectal cancer
The team emphasizes the importance of making these distinctions. fusobacteria subspecies. This group of bacteria is often associated with colorectal cancer.
Some variants were particularly common in colorectal cancer samples from certain geographic regions, such as Asia, while some carried different disease-associated genes, the researchers explained.
Fusobacterium nucleatum subspecies animal Enrichment was consistently seen in colorectal cancer patients from all continents.
Previous research has identified patterns of bacteria, fungi, and viruses that occur more frequently in colorectal cancer patients and make up the “carcinogenic microbiome.”
Another study found that the bacterial toxin colibactin increased the incidence of colorectal cancer in young people.
