Linking nasopharyngeal and oropharyngeal microbiota to immune responses during influenza-like illness in an aging population

Older adults are vulnerable to influenza-like illness (ILI). To study how infection shapes the respiratory microbiota, we profiled nasopharyngeal (NP) and oropharyngeal (OP) communities alongside local immune mediators in adults aged 60–88, comparing asymptomatic, ILI, and recovery states. NP communities clustered into three community state types (CSTs): Moraxella -dominated (CST-1), Haemophilus/Streptococcus/Staphylococcus -associated (CST-2), and Corynebacterium/Dolosigranulum -dominated (CST-3). During infection, compositional shifts were restricted to the NP niche, where CST-1 and CST-2 were more frequent. Streptococcus, Haemophilus and Moraxella were positively associated with inflammatory and interferon-related mediators, including IL-6, CXCL9 and CXCL10, while Corynebacterium showed negative associations. Immune activation was strong in the NP but limited in the OP, and stayed above healthy levels at follow-up, suggesting incomplete recovery. NP composition was also associated with symptom burden, viral and bacterial co-detection and smoking status. These site-specific microbiota-immune relationships identify the nasopharynx as the primary site of immune modulation during ILI in older adults.