The Therapeutic Administration of Lactobacillus brevis ZG2488 Suppresses Influenza A Virus Replication Through a Viability-Dependent Host Transcriptional Modulation Mechanism

Influenza A virus (IAV) remains a major global threat, highlighting the need for host-targeted antiviral strategies. While some probiotics offer prophylactic protection, their therapeutic potential post-infection is poorly understood. Here, we investigated human-derived Lactobacillus brevis ZG2488 for its antiviral potential against IAV. Strikingly, a more pronounced reduction in viral titer was observed when live bacteria were administered therapeutically post-infection, compared to preventive pretreatment. Transcriptomic analysis suggested that the therapeutic effect of viable bacteria was associated with a modulated host response, including the downregulation of specific host factors implicated in viral replication (e.g., KPNA2, NUP98, EIF2S1) and a delayed interferon-beta (IFNB1) induction. In contrast, preventive effects appeared to be mediated by heat-stable components. These findings highlight a viability-dependent mode of action for L. brevis ZG2488 and contribute to the growing evidence that certain probiotics may exert antiviral effects through targeted host modulation rather than solely through broad immune activation.