The Archaeome’s Role in Colorectal Cancer: Unveiling the DPANN Group and Investigating Archaeal Functional Signatures

Abstract

Background and Aims: Gut microbial imbalances are linked to colorectal cancer (CRC), but archaea’s role remains underexplored. Here, using previously published metagenomic data from different populations including Austria, Germany, Italy, Japan, China, and India, we performed bioinformatic and statistical analysis to identify archaeal taxonomic and functional signatures related to CRC. Methods: We analyzed published fecal metagenomic data from 390 subjects, comparing the archaeomes of CRC and healthy individuals. We conducted a biostatistical analysis to investigate the relationship between Candidatus Mancarchaeum acidiphilum (DPANN superphylum) and other archaeal species associated with CRC. Using the Prokka tool, we annotated the data focusing on archaeal genes, subsequently linking them to CRC and mapping them against UniprotKB and GO databases for specific archaeal gene functions. Results: Our analysis identified enrichment of methanogenic archaea in healthy subjects, with an exception for Methanobrevibacter smithii, which correlated with CRC. Notably, CRC showed a strong association with archaeal species, particularly Natrinema sp. J7-2, Ferroglobus placidus, and Candidatus Mancarchaeum acidiphilum. Furthermore, the DPANN archaeon exhibited a significant correlation with other CRC-associated archaea (p Candidatus Mancarchaeum acidiphilum, Natrinema sp. J7-2, and Ferroglobus placidus emerge as potential archaeal biomarkers. Archaeal proteins may also offer gut protection, underscoring archaea’s role in CRC dynamics.

Keywords

• colorectal cancer
• gut microbiome
• archaea
• DPANN group
• MvhB-type polyferredoxin
• <i>Ferroglobus placidus</i>