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bioRxiv · 10.1101/2025.02.05.636567

Human gut microbiota subspecies carry implicit information for in-depth microbiome research

Trickovic, M.·Kieser, S.·Zdobnov, E. M.·Trajkovski, M.
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Abstract

Microbial strains from same species can have distinct functional characteristics owing to their different gene content. As the highest resolution, strains are mainly host-specific, thus obscuring unbiased associations, and hindering deductive research. Here, we comprehensively define the human gut microbiota at consistently-annotated subspecies resolution in an unbiased, cohort-independent manner, and demonstrate that we can generalize across distinct populations worldwide while maintaining specificity and improving interstudy reproducibility. We developed panhashome, a sketching-based method for rapid subspecies quantification and identification of genes that drive the intraspecies variations, and showed that subspecies carry implicit information undetectable at species level. By meta-analysis of colorectal cancer (CRC) datasets, we identified disease-associated subspecies whose sibling subspecies or species are not. Subspecies-based machine-learning CRC diagnostic algorithm outperformed species-level methods by leveraging the unique subspecies-level information. This subspecies catalogue allows identification of genes that drive the functional differences between subspecies as fundamental step in mechanistically understanding microbiome-phenotype interactions.

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Trickovic, M., Kieser, S., Zdobnov, E. M., Trajkovski, M.. 2025-02-08. Human gut microbiota subspecies carry implicit information for in-depth microbiome research. https://doi.org/10.1101/2025.02.05.636567

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