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.