Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 21 August 2023 / Approved: 22 August 2023 / Online: 22 August 2023 (11:48:13 CEST)

A peer-reviewed article of this Preprint also exists.

Mathlouthi, N.E.H.; Belguith, I.; Yengui, M.; Oumarou Hama, H.; Lagier, J.-C.; Ammar Keskes, L.; Grine, G.; Gdoura, R. The Archaeome’s Role in Colorectal Cancer: Unveiling the DPANN Group and Investigating Archaeal Functional Signatures. Microorganisms 2023, 11, 2742. Mathlouthi, N.E.H.; Belguith, I.; Yengui, M.; Oumarou Hama, H.; Lagier, J.-C.; Ammar Keskes, L.; Grine, G.; Gdoura, R. The Archaeome’s Role in Colorectal Cancer: Unveiling the DPANN Group and Investigating Archaeal Functional Signatures. Microorganisms 2023, 11, 2742.

Abstract

Background & Aims: Gut microbial imbalances are linked to colorectal cancer (CRC), but archae-‎a's role remains underexplored. Here, we performed bioinformatic and statistical analysis looking ‎for archaeal taxonomic and functional signatures related to CRC. Methods: We analyzed pub-‎lished fecal metagenomic data from 390 subjects, comparing the archaeomes of CRC and healthy ‎individuals. We conducted a biostatistical analysis to investigate the relationship between Candi-‎datus 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 ar-‎chaeal 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 ar-‎chaeon exhibited a significant correlation with other CRC-associated archaea (p < 0.001). Func-‎tionally, we found a marked association between MvhB-type polyferredoxin and colorectal can-‎cer. We also highlighted the association of archaeal proteins involved in the biosynthesis of leucine ‎and the galactose metabolism process with the healthy phenotype. Conclusion: The archaeomes ‎of CRC patients show identifiable alterations, including a decline in methanogens and an increase ‎in Halobacteria species. MvhB-type polyferredoxin, linked with CRC and species like 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; Ferroglobus placidus; VNatrinema sp. J7-2; Archaeal biomarker

Subject

Medicine and Pharmacology, Oncology and Oncogenics

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