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Pneumonia remains a major infectious disease, with K. pneumoniae posing serious threats, especially under antibiotic-induced dysbiosis. The team led by Dr. Ya-Jen Chang at the Institute of Biomedical Sciences, Academia Sinica, further explored the role of the lung microbiota in protection against pneumonia.

Pneumonia remains a major infectious disease, with K. pneumoniae posing serious threats, especially under antibiotic-induced dysbiosis. The team led by Dr. Ya-Jen Chang at the Institute of Biomedical Sciences, Academia Sinica, further explored the role of the lung microbiota in protection against pneumonia.

Using the mouse model, the team shows that antibiotic-induced lung dysbiosis increases susceptibility to infection. Mechanistically, lung microbiota-derived SCFAs (Short-Chain Fatty Acids) engage FFAR2 (Free Fatty Acid Receptor 2) on alveolar macrophages (AMs), promoting IL-1β production and γδ T cell IL-17A responses against infection. Conversely, lung dysbiosis-induced reductions in SCFA levels or FFAR2 deficiency compromise this protective network. These findings reveal a lung-intrinsic microbiota–immune axis and highlight SCFA supplementation or FFAR2 targeting as potential therapeutic strategies to restore mucosal defense after antibiotic perturbation.

The study was led by Dr. Ya-Jen Chang from the Institute of Biomedical Sciences, Academia Sinica, and MS student Ting-Chieh Huang from the Graduate Institute of Microbiology & Immunology, NDMU. This research was supported by Academia Sinica and the National Science and Technology Council, and was published in Theranostics on Mar 12, 2026.