Abstract
The InBLOOM project investigates the role of the blood microbiome in colorectal cancer (CRC) etiology and detection. Based on a case-control study including 100 CRC patients, 100 with intestinal adenomas and 100 healthy controls, the project builds on preliminary 16S rRNA analyses and detailed lifestyle and dietary data. Using shotgun metagenomics, InBLOOM will characterize the taxonomy, function, and origin of circulating microbial DNA in blood. Multivariate models will link blood microbiome features to CRC risk, identify potential diagnostic biomarkers, and assess associations with lifestyle factors. This innovative approach aims to clarify the microbial contribution to the adenoma–carcinoma sequence and improve CRC prevention strategies.
Results achieved
The InBLOOM project successfully achieved all its planned scientific objectives, providing novel insights into the role of the circulating blood microbiome, intended as circulating microbial DNA, in colorectal cancer (CRC). By combining high-resolution shotgun metagenomic sequencing with epidemiological, clinical, and lifestyle data, the project has substantially advanced the understanding of the systemic microbial signatures associated with colorectal carcinogenesis and their potential clinical relevance. The project generated one of the largest and most comprehensive shotgun metagenomic datasets currently available on circulating microbial DNA in blood samples from patients with colorectal cancer, colorectal adenomas, and healthy controls. This unique resource enabled the characterization of circulating microbial DNA with unprecedented taxonomic resolution and provided robust evidence that circulating microbial DNA profiles differ significantly among healthy individuals, patients with colorectal adenomas, and CRC patients. These findings support the hypothesis that microbial DNA detected in the bloodstream reflects alterations in host–microbiota interactions and intestinal barrier function occurring during colorectal tumorigenesis. The project identified reproducible microbial signatures associated with colorectal cancer, including an increased representation of opportunistic microorganisms, enrichment of Streptococcus DNA, and a higher abundance of Moraxella osloensis. Through targeted enrichment, additional sequencing, and metagenomic assembly, it was possible to achieve species-level identification of several Streptococcus taxa, including Streptococcus gallolyticus, Streptococcus sanguinis, Streptococcus oralis, Streptococcus salivarius, and Streptococcus parasanguinis, microorganisms that have previously been associated with colorectal cancer or systemic infections. These results substantially improve the biological interpretation of circulating microbial DNA signals and strengthen the evidence supporting microbial translocation as a feature of colorectal cancer. The project also demonstrated that circulating microbial DNA changes progressively during disease progression. Patients with metastatic colorectal cancer exhibited significantly lower microbial diversity and greater inter-individual heterogeneity of circulating microbial DNA profiles than patients with localized disease, suggesting progressive impairment of epithelial barrier integrity and increasing variability in microbial translocation dynamics during tumour progression. These findings provide novel insights into the biological mechanisms linking microbiota alterations with colorectal cancer progression and systemic host responses. Beyond the identification of disease-associated microbial signatures, InBLOOM established a robust experimental, bioinformatic, and statistical framework for the analysis of circulating microbial DNA from low-biomass blood samples. The project developed standardized workflows for contamination control, shotgun metagenomic sequencing, taxonomic profiling, machine-learning analyses, and integration with epidemiological variables, providing methodological advances that will support future studies investigating circulating microbial DNA in cancer and other diseases. The integration of microbiome, clinical, and lifestyle data further contributed to a more comprehensive understanding of the interactions between environmental exposures, host factors, microbial translocation, and colorectal cancer. In parallel, the project generated publicly available sequencing datasets and reproducible analytical pipelines, ensuring that the scientific resources produced within InBLOOM will remain available to the research community and facilitate future investigations. The scientific outcomes of the project have been disseminated through peer-reviewed publications, presentations at national and international scientific meetings, and open-access deposition of sequencing data. In addition to advancing the biological understanding of colorectal cancer, the project provides a strong proof-of-concept for the use of circulating microbial DNA as a minimally invasive source of biomarkers. The microbial signatures identified by InBLOOM represent promising candidates for the development of targeted molecular diagnostic assays, potentially based on cost-effective technologies such as digital PCR, and may contribute to improved colorectal cancer screening, early diagnosis, patient stratification, disease monitoring, and precision medicine approaches. Overall, the InBLOOM project has established a new framework for investigating circulating microbial DNA in colorectal cancer, demonstrating its potential both as a window into host–microbiota interactions and as a clinically relevant source of minimally invasive biomarkers for CRC prevention and management.Project details
Unibo Team Leader: Simone Rampelli
Unibo involved Department/s:
Dipartimento di Farmacia e Biotecnologie
Coordinator:
ALMA MATER STUDIORUM - Università di Bologna(Italy)
Total Eu Contribution: Euro (EUR) 229.208,00
Total Unibo Contribution: Euro (EUR) 129.314,00
Project Duration in months: 24
Start Date:
30/11/2023
End Date:
28/02/2026
