{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:30:49Z","timestamp":1792290649316,"version":"4.4.0"},"reference-count":59,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["21ck0106701h0001 22ck0106701h0002 23ck0106701h0003 25ck0106002h0001"],"award-info":[{"award-number":["21ck0106701h0001 22ck0106701h0002 23ck0106701h0003 25ck0106002h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Extracellular Vesicle"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Bacterial extracellular vesicles (EVs) are emerging mediators of host\u2013microbe communication; however, their role in human disease remains unclear. Here, we identify two bacterial small tRNAs (tsRNAs) enriched in gut commensal\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    \u2010derived EVs (KpEVs) that are markedly elevated in the serum of patients with hepatocellular carcinoma (HCC). These tsRNAs suppress the production of nitric oxide (NO) by macrophages, a critical antitumor molecule. Notably, KpEVs reach the liver more efficiently than bacterial cells, thus facilitating bacterial translocation from the gut by inducing distinctive immunosuppressive macrophages. Mechanistically, KpEVs drive an M2\u2010like macrophage phenotype, enhance phagocytosis, and inhibit both NO production and caspase\u20101\u2010dependent pyroptosis during infection. The results show that KpEVs shape a liver microenvironment promoting gut\u2013liver bacterial translocation, which may also influence HCC progression. Our study uncovers a previously unrecognized strategy by which\n                    <jats:italic>K. pneumoniae<\/jats:italic>\n                    exploits EVs to modulate host immunity of distant organs, highlighting tsRNAs as potential biomarkers and therapeutic targets.\n                  <\/jats:p>","DOI":"10.1002\/jev2.70262","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T12:38:56Z","timestamp":1774528736000},"source":"Crossref","is-referenced-by-count":6,"title":["Gut Commensal\n                    <i>Klebsiella pneumoniae<\/i>\n                    Extracellular Vesicles Shape a Liver Microenvironment Conducive to Gut\u2010Liver Bacterial Translocation and Pro\u2010Tumorigenic Processes"],"prefix":"10.1002","volume":"15","author":[{"given":"Shogo","family":"Tsubaki","sequence":"first","affiliation":[{"name":"Transkingdom Signaling Research Unit, Division of Host Defense Mechanism Tokai University School of Medicine  Isehara Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sho","family":"Nashimoto","sequence":"additional","affiliation":[{"name":"Transkingdom Signaling Research Unit, Division of Host Defense Mechanism Tokai University School of Medicine  Isehara Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rika","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Immunology, Division of Host Defense Mechanism Tokai University School of Medicine  Isehara Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Touya","family":"Toyomoto","sequence":"additional","affiliation":[{"name":"Transkingdom Signaling Research Unit, Division of Host Defense Mechanism Tokai University School of Medicine  Isehara Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyasu","family":"Tsutsuki","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Graduate School of Medical Sciences Kumamoto University  Chuo\u2010ku Kumamoto Japan"},{"name":"Department of Clinical Microbiology, Faculty of Life Sciences Kumamoto University  Chuo\u2010ku Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Head and Neck, Esophageal Medical Oncology \/ Department of Gastrointestinal Medical Oncology National Cancer Center Hospital  Chuo\u2010ku Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Laboratory of Integrative Oncology, National Cancer Center Research Institute  Chuo\u2010ku Tokyo Japan"},{"name":"Department of Oncogenesis and Growth Regulation Research Institute Osaka International Cancer Institute  Chuo\u2010ku Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiminori","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Hepatology Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital  Bunkyo\u2010ku Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Oshima","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapeutics Keio University Faculty of Pharmacy  Minato\u2010ku Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Laboratory of Integrative Oncology, National Cancer Center Research Institute  Chuo\u2010ku Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuji","family":"Okusaka","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Oncology National Cancer Center Hospital  Chuo\u2010ku Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minoru","family":"Esaki","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery National Cancer Center Hospital  Chuo\u2010ku Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiro","family":"Kawai","sequence":"additional","affiliation":[{"name":"Preferred Medicine, Inc.  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