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Here, we uncover a previously unrecognized role of\n                    <jats:italic>Bacteroides intestinalis<\/jats:italic>\n                    in restraining extra\u2010intestinal tumor growth via OMVs enriched in sphingosine (SP), a bioactive lipid that directly binds to ATP5F1A\u2014a subunit of the mitochondrial ATP synthase\u2014to enhance NK cell function. This microbial lipid\u2010ATP synthase interaction augments mitochondrial efficiency, reduces reactive oxygen species (ROS) production, and potently upregulates IFN\u2010\u03b3secretion in NK cells, driving increased cytotoxicity and tumor infiltration. Remarkably, OMVs from\n                    <jats:italic>B. intestinalis<\/jats:italic>\n                    or SP administration greatly inhibit murine tumor growth, while their combination with anti\u2010PD\u20101 therapy enhances systemic antitumor immunity. This study establishes the specific immune activation ability for gut microbial OMVs and highlights microbiota\u2010derived lipid\u2010based immunotherapies.\n                  <\/jats:p>","DOI":"10.1002\/advs.202520095","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T12:01:52Z","timestamp":1776081712000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Microbial Lipid\u2010ATP Synthase Axis Fuels NK Cell Antitumor Activity"],"prefix":"10.1002","volume":"13","author":[{"given":"Kaiyuan","family":"Yu","sequence":"first","affiliation":[{"name":"Tianjin Institute of Immunology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), School of Basic Medical Sciences, Tianjin Medical University, State Key Laboratory of Experimental Hematology Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin 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