Shared gut virome profiles highlight potential early colorectal cancer markers in HIV-helminth co-infection

Background: In regions with high HIV and helminth prevalence, co-infection may reshape the gut virome in ways that promote oncogenic processes. Characterizing these alterations may identify early colorectal cancer (CRC) biomarkers in high-risk populations. Methods: Stool-derived metagenomic data from CRC patients, HIV-infected, helminth-infected, HIV-helminth co-infected individuals, and uninfected controls were analyzed. Viral taxa were quantified at family and genus levels using a metagenomic coassembly pipeline. Hierarchical clustering and heatmap visualisation compared abundance patterns across groups. Results: CRC samples formed distinct clusters with altered abundance of Siphoviridae (−1.6 ± 0.41; q = 0.0013), Podoviridae (2.3 ± 0.83; q = 0.031), unclassified Caudovirales (−1.6 ± 0.51; q = 0.010), Virus sp. ctWxR2 (−14.7 ± 5.04; q = 0.019), and CrAss-like virus sp. ctt4r3 (22.9 ± 5.00; q = 9.9×10⁻⁵). HIV-helminth co-infected samples formed a subcluster overlapping CRC, showing similar enrichments in Siphoviridae (−2.0 ± 0.39; q = 5.3×10⁻⁶), unclassified Caudovirales (−2.6 ± 0.48; q = 4.7×10⁻⁶), Virus sp. ctWxR2 (−21.1 ± 4.79; q = 0.00011), and CrAss-like virus sp. ctt4r3 (24.8 ± 4.78; q = 2.2×10⁻⁷). HIV-only samples resembled controls, while helminth-only samples displayed intermediate profiles. Conclusion: HIV-helminth co-infected individuals showed closely aligned profiles with CRC, indicating that chronic immune perturbation may create virome states resembling early CRC-associated dysbiosis. These shared viral signatures could serve as potential non-invasive biomarkers for CRC risk stratification in high-burden settings. Longitudinal analyses are needed to clarify temporal dynamics and identify the bacterial hosts and functional pathways through which viral/phage restructuring may promote CRC development.