Abstract
The larynx is vital for swallowing, breathing, coughing, and voice production, supported by its unique microbial and immunological environment. We hypothesized the existence of a gut-larynx axis, where resident gut and laryngeal microbiota influence immune modulation in the larynx. To test this, conventionally raised, wild-type C57BL/6 J mice were treated with an oral antibiotic regimen to disrupt gut microbiota and compared with untreated controls. Antibiotic treatment significantly disrupted gut microbiota but left laryngeal microbiota largely unaffected. However, antibiotic-treated mice showed notable changes in laryngeal epithelial and immune cells, as well as fibroblasts. Differential gene expression analysis revealed alterations in pathways related to epithelial barrier integrity, immune signaling, and bacterial response. Gene regulatory network analysis identified significant changes in regulons Etv4(+), Irf3(+), Hltf(+), Mga(+), and Nfil3(+). Additionally, cell-cell communication, particularly immune-epithelial interactions, was altered, with integrin-mediated signaling emerging as a key pathway. These findings suggest that gut and laryngeal microbiota may synergistically modulate immune responses, highlighting the importance of gut-larynx interactions in respiratory immunity. IMPORTANCE: This study investigates the gut-larynx axis, revealing how gut dysbiosis impacts immune responses in the larynx. Although laryngeal microbiota remained stable, significant immunological and cellular changes occurred following gut microbiota disruption. Transcriptomic alterations in epithelial integrity, immune signaling, and cell communication underscore the systemic impact of gut dysbiosis. The identification of integrin-mediated signaling as a key pathway in immune-epithelial interactions emphasizes the complexity of host-microbe dynamics. These findings suggest that gut health plays a critical role in shaping respiratory immunity, providing a foundation for future research into microbiota-driven immune modulation in the upper airway.