摘要:SummaryComparing the nasal microbiome of healthy individuals and chronic rhinosinusitis (CRS) patients revealedDolosigranulum pigrumas a species clearly associated with nasal health, although isolates obtained from healthy individuals are scarce. In this study, we explored the properties of this understudied lactic acid bacterium by integrating comparative genomics, habitat mining, cultivation, and functional characterization of interaction capacities. Mining 10.000 samples from the Earth Microbiome Project of 17 habitat types revealed thatDolosigranulumis mainly associated with the human nasal cavity.D. pigrumAMBR11 isolated from the nose of a healthy individual exerted antimicrobial activity againstStaphylococcus aureus, decreased proinflammatory cytokine production in airway epithelial cells, andGalleria mellonellalarvae mortality induced by this important nasal pathobiont. Furthermore, the strain protected the nasal barrier function in a mouse model using interleukin-4 as disruptive cytokine. Hence,D. pigrumAMBR11 is a mutualist with high potential as topical live biotherapeutic product.Graphical abstractDisplay OmittedHighlights•Habitat mining reveals thatDolosigranulum pigrumprefers the human nasal cavity•D. pigrumAMBR11 has immunomodulatory and nasal barrier-enhancing capacities•D. pigrumAMBR11 exerts antimicrobial activity againstS. aureusImmunology; Microbiology; Microbiome