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While it is widely acknowledged that probiotics can modulate the host response to protect the host against infectious disease, the prophylactic efficacy on respiratory viral infection and the detailed mechanism remains elusive.\n              <jats:italic>Lactobacillus<\/jats:italic>\n              , the most commonly used probiotic widely applied in food production, has garnered significant attention. In our study utilizing both C57BL\/6 and BALB\/c mouse models, we explored the protective effect against two strains of influenza virus, A\/Mink\/China\/01\/2014(H9N2) and A\/California\/04\/2009(H1N1), through the administration of\n              <jats:italic>Lactiplantibacillus plantarum<\/jats:italic>\n              strain 16 (\n              <jats:italic>L. plantarum<\/jats:italic>\n              16) and\n              <jats:italic>Lacticaseibacillus rhamnosus<\/jats:italic>\n              strain P118 (\n              <jats:italic>L. rhamnosus<\/jats:italic>\n              P118), aiming to identify robust probiotic strains with antiviral properties. Our findings indicate that administering\n              <jats:italic>L. plantarum<\/jats:italic>\n              16 or\n              <jats:italic>L. rhamnosus<\/jats:italic>\n              P118 alone does not provide sufficient protection against influenza. However, the co-administration of\n              <jats:italic>L. plantarum<\/jats:italic>\n              16 and\n              <jats:italic>L. rhamnosus<\/jats:italic>\n              P118 dramatically reduces viral titers in the respiratory tract and lung, thereby markedly alleviating the clinical symptoms, improving prognosis, and reducing mortality. The mechanisms underlying this effect involve the modulation of host gut microbiota and metabolism through the co-administration of\n              <jats:italic>L. plantarum<\/jats:italic>\n              16 and\n              <jats:italic>L. rhamnosus<\/jats:italic>\n              P118, resulting in enrichment of Firmicutes and enhancement of phenylalanine-related metabolism, ultimately leading to an augmentation of the antiviral immune response. Notably, we identified that the circulating metabolic molecule 2-Hydroxycinnamic acid plays a significant role in combating influenza. Our data suggest the potential utility of\n              <jats:italic>L. plantarum<\/jats:italic>\n              16 and\n              <jats:italic>L. rhamnosus<\/jats:italic>\n              P118 two-bacterium or 2-Hydroxycinnamic acid in preventing influenza.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                Vaccination represents the most optimal strategy to control influenza. Nevertheless, influenza viruses constantly evolve due to antigenic drift and shift, leading to the need for regular updates on influenza vaccines. Additionally, vaccination failure poses significant challenges to influenza prevention. Therefore, it is essential and beneficial to identify novel or universal antiviral measures to protect against influenza. While cumulative data suggest that probiotics offer protection against infectious diseases, the specific mechanisms, such as the effective metabolites or components, remain largely unknown. Our research discovered the capacity of combinational two-bacterium\n                <jats:italic>Lactiplantibacillus plantarum<\/jats:italic>\n                16 and\n                <jats:italic>Lacticaseibacillus rhamnosus<\/jats:italic>\n                P118 to fight against influenza infection in a mouse model. The protection may occur through modulating the host\u2019s gut microbiota and metabolism, further influencing the host\u2019s antiviral immune response. Notably, we have identified a novel metabolic molecule, 2-Hydroxycinnamic acid, capable of enhancing antiviral response and restricting viral replication\n                <jats:italic>in vivo<\/jats:italic>\n                .\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/jvi.00950-24","type":"journal-article","created":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T13:04:46Z","timestamp":1726059886000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":14,"title":["Oral co-administration of\n            <i>Lactiplantibacillus plantarum<\/i>\n            16 and\n            <i>Lacticaseibacillus rhamnosus<\/i>\n            P118 improves host defense against influenza A virus infection"],"prefix":"10.1128","volume":"98","author":[{"given":"Meiqing","family":"Han","sequence":"first","affiliation":[{"name":"Department of Veterinary Medicine and Institute of Preventive 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