{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:44:55Z","timestamp":1792154695547,"version":"4.4.0"},"reference-count":60,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32222084"],"award-info":[{"award-number":["32222084"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["iMeta"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Carbapenem\u2010resistant\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    (CRKP) is a major multidrug\u2010resistant pathogen with limited treatment options. Plant\u2010derived natural products have broad biological activities, but their protective effects against extraintestinal multidrug\u2010resistant bacterial infections remain poorly understood. Herein, we show that selected plant\u2010derived natural products protect mice against CRKP pulmonary infection by remodeling the gut microbiota. Fecal microbiota transplantation and microbiota\u2010depletion experiments demonstrated that this protection was microbiota dependent, with\n                    <jats:italic>Lactobacillus<\/jats:italic>\n                    emerging as a key genus associated with reduced pulmonary bacterial burden. Among four isolated\n                    <jats:italic>Lactobacillus<\/jats:italic>\n                    species,\n                    <jats:italic>Lactobacillus murinus<\/jats:italic>\n                    (\n                    <jats:italic>L. murinus<\/jats:italic>\n                    ) conferred the strongest protection against CRKP infection. Mechanistically,\n                    <jats:italic>L. murinus<\/jats:italic>\n                    \u2010derived membrane vesicles (MVs) delivered the small RNA mim\u2010miR\u201021a\u20105p to pulmonary macrophages, where it targeted\n                    <jats:italic>PDCD4<\/jats:italic>\n                    and activated the Nrf2\/SOD2 antioxidant pathway. This signaling cascade preserved mitochondrial oxidative phosphorylation, promoted an M2\u2010like macrophage phenotype, and ultimately restricted CRKP infection. Consistent with these findings, intestinal\n                    <jats:italic>Lactobacillus<\/jats:italic>\n                    , particularly\n                    <jats:italic>L. murinus<\/jats:italic>\n                    , was reduced in patients with CRKP infection compared with healthy controls. Collectively, our findings reveal a mechanism by which plant\u2010derived natural products enhance host resistance to CRKP through microbiota remodeling and identify\n                    <jats:italic>L. murinus<\/jats:italic>\n                    \u2010derived small RNAs and membrane vesicles as key mediator of this gut\u2010lung protective axis.\n                  <\/jats:p>","DOI":"10.1002\/imt2.70184","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T11:48:22Z","timestamp":1792151302000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>Lactobacillus<\/i>\n                    derived small RNAs protect against\n                    <i>Klebsiella pneumoniae<\/i>\n                    infection"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0067-6337","authenticated-orcid":false,"given":"Tingting","family":"Xu","sequence":"first","affiliation":[{"name":"Jiangsu Co\u2010innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses College of Veterinary Medicine, Yangzhou University Yangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuying","family":"Tao","sequence":"additional","affiliation":[{"name":"Jiangsu Co\u2010innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses College of Veterinary Medicine, Yangzhou University Yangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Fang","sequence":"additional","affiliation":[{"name":"Jiangsu Co\u2010innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses College of Veterinary Medicine, Yangzhou University Yangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jiangsu Co\u2010innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses College of Veterinary Medicine, Yangzhou University Yangzhou China"},{"name":"Jiangsu Key Laboratory of Zoonosis Yangzhou University Yangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Jiangsu Co\u2010innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses College of Veterinary Medicine, Yangzhou University Yangzhou China"},{"name":"Jiangsu Key Laboratory of Zoonosis Yangzhou University Yangzhou China"},{"name":"Jiangsu Interdisciplinary Center for Zoonoses and Biosafety Yangzhou University Yangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9622-6471","authenticated-orcid":false,"given":"Yuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Jiangsu Co\u2010innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses College of Veterinary Medicine, Yangzhou University Yangzhou China"},{"name":"Jiangsu Key Laboratory of Zoonosis Yangzhou University Yangzhou China"},{"name":"Jiangsu Interdisciplinary Center for Zoonoses and Biosafety Yangzhou University Yangzhou 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