Cryptic viral elements in probiotic genomes: Latent regulatory modules and emerging tools for microbiome biotechnology

Cryptic viral elements (CVEs) are virus-derived genomic sequences integrated into bacterial chromosomes that have lost the ability to form infectious particles but are retained through evolutionary processes. Emerging evidence indicates that some CVEs are functionally active rather than inert, contributing to stress adaptation, gene regulation, and genome stability in certain bacterial systems, including probiotic genera such as Lactobacillus and Bifidobacterium . For instance, defective prophage regions have been associated with oxidative stress tolerance and persistence under nutrient-limited conditions, although these roles remain context- and strain-dependent. This review critically examines the origin, diversity, and functional relevance of CVEs in probiotic genomes, distinguishing experimentally supported functions from inferred roles in metabolic flexibility and horizontal gene transfer. Current bioinformatic approaches for CVE detection are evaluated, with emphasis on their limitations, including sequence degeneration and annotation biases. While CVEs have been proposed as potential tools for strain improvement and microbiome modulation, direct experimental validation remains limited. Key challenges include incomplete functional characterization and unresolved biosafety concerns. Addressing these gaps will be essential to assess the feasibility of leveraging CVEs in applied microbiology and biotechnology.