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Whereas gut bacterial dysbiosis exacerbates pulmonary infections, the role of gut fungi in modulating lung immunity remains understudied. Here, we demonstrate that antibiotic-induced gut fungal expansion aggravates pneumonia by enhancing alveolar macrophage-driven inflammation via Dectin-1 signaling. Clinical analyses demonstrated that pneumonia patients receiving ineffective prehospital antibiotic therapy showed gut bacterial depletion accompanied by fungal overgrowth (primarily Candida spp.), with a positive correlation observed between fungal abundance and hospitalization duration. In murine models, antibiotic-induced gut microbiota disruption promoted fungal proliferation, subsequently upregulating Dectin-1 expression in alveolar macrophages. This activation triggered excessive IL-1\u03b2 secretion and neutrophil recruitment, exacerbating lung injury and mortality. Our results demonstrated that both antifungal intervention and Dectin-1 knockout reversed these pathological effects, resulting in improved survival rates, reduced bacterial dissemination, and attenuated inflammatory cytokine levels. Mechanistically, gut fungi remotely potentiated pulmonary inflammation through the alveolar macrophage \u201cDectin-1\/IL-1\u03b2\/neutrophil axis\u201d, independent of pathogen clearance. Although recent studies have begun to uncover \u201cmycobiome-lung\u201d disease associations, our findings specifically demonstrate that fungal dysbiosis mediates the \u201cgut-lung axis\u201d during multidrug-resistant K. pneumoniae infections. This study provides mechanistic insights into microbial crosstalk and advances translational approaches for combating antibiotic-exacerbated pneumonias.<\/jats:p>","DOI":"10.1093\/ismejo\/wraf181","type":"journal-article","created":{"date-parts":[[2025,8,16]],"date-time":"2025-08-16T10:19:51Z","timestamp":1755339591000},"source":"Crossref","is-referenced-by-count":9,"title":["Dysbiotic gut fungi exacerbate <i>Klebsiella pneumoniae<\/i> lung infection via Dectin-1-mediated alveolar macrophage hyperactivation"],"prefix":"10.1093","volume":"19","author":[{"given":"Shengfu","family":"He","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University , Hefei, Anhui 230022 ,","place":["China"]},{"name":"Department of Infectious Diseases & Anhui Center for Surveillance of Bacterial Resistance, The First Affiliated Hospital of Anhui Medical University , Hefei, Anhui 230022 ,","place":["China"]},{"name":"Anhui Province Key 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The First Affiliated Hospital of Anhui Medical University , Hefei, Anhui 230022 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases & Anhui Center for Surveillance of Bacterial Resistance, The First Affiliated Hospital of Anhui Medical University , Hefei, Anhui 230022 ,","place":["China"]},{"name":"Anhui Province Key Laboratory of Infectious Diseases & Institute of Bacterial Resistance & Institute of Infectious Diseases, Anhui Medical University , Hefei, Anhui 230022 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renyu","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University , Hefei, Anhui 230022 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University , Hefei, Anhui 230022 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases & Anhui Center for Surveillance of Bacterial Resistance, The First Affiliated Hospital of Anhui Medical University , Hefei, Anhui 230022 ,","place":["China"]},{"name":"Anhui Province Key Laboratory of Infectious Diseases & Institute of Bacterial Resistance & Institute of Infectious Diseases, Anhui Medical University , Hefei, Anhui 230022 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifen","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases & Anhui 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