The human gut microbiome plays a central role in host homeostasis, but its contribution to cancer remains under-characterized at fine taxonomic resolution. While previous studies have focused primarily on species-level associations, few studies are now investigating untargeted strain signals in the gut microbiome of patients with colorectal cancer.
Here, we performed an untargeted strain-level meta-analysis of metagenomic sequencing data from seven different datasets of fecal samples of patients with haematological cancer (different types of Lymphoma and Leukemia) and matched healthy controls. We used a combination of marker-based reference approach and assembly-based approach (i.e., to generate metagenome assembled genomes (MAGs)) to profile microbial communities at the species, strain, and functional gene levels.
We generated a catalogue of 14,647 medium to high quality cancer associated MAGs. Significant reductions in alpha-diversity and distinct beta-diversity were observed in both cancer types compared to control. Several pathobionts, especially Enterocloster boltae and Clostridium innocuum were strongly and consistently enriched in both Leukemia and Lymphoma, while Escherichia coli was only enriched in Lymphoma. Certain species that were not differentially abundant at the species level displayed strong cancer-specific strain-level signals, especially abundant members of the gut microbiome such as Bacteroides spp., possibly related to a strain-level adaptation to cancer-related dysbiosis.
Our findings highlight the importance of moving beyond species-level resolution to detect strain-specific signals that would otherwise remain hidden and underscores the potential for strain-resolution to inform cancer diagnostics and therapeutic strategies.

Co-authors: None