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Through fermentation, the microbiota produces and releases microbial metabolites such as short-chain fatty acids (SCFAs), which can affect host homeostasis. There is growing evidence that the gut microbiome can have a major impact on cancer. Specific gut microbial composition and metabolites are associated with tumor status in the host. However, their effects on the antitumor response have scarcely been investigated. Natural killer (NK) cells play an important role in antitumor immunity due to their ability to directly identify and eliminate tumor cells. Methods: The aim of this study was to investigate the effects of SCFAs on antitumoral NK cell activity, using NK-92 cell line. Results: Here, we describe how SCFAs can boost antitumoral NK cell activity. The SCFAs induced the release of NK extracellular vesicles and reduced the secretion of the anti-inflammatory cytokine IL-10. The SCFAs also increased the cytotoxicity of the NK cells against multiple myeloma cells. Conclusions: Our results indicate, for the first time, the enormous potential of SCFAs in regulating antitumoral NK cell defense, where modulation of the SCFAs\u2019 production could play a fundamental role in cancer immunotherapy.<\/jats:p>","DOI":"10.3390\/jcm13133885","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T11:23:55Z","timestamp":1719919435000},"page":"3885","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Microbiota-Derived Short-Chain Fatty Acids Boost Antitumoral Natural Killer Cell Activity"],"prefix":"10.3390","volume":"13","author":[{"given":"Marina","family":"P\u00e9rez","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, 50009 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8467-0356","authenticated-orcid":false,"given":"Berta","family":"Buey","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Fisiolog\u00eda y Medicina Legal y Forense, Facultad de Veterinaria, Universidad de Zaragoza, 50013 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Corral","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, 50009 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Giraldos","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, 50009 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5797-3909","authenticated-orcid":false,"given":"Eva","family":"Latorre","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, 50009 Zaragoza, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria de Arag\u00f3n (IIS Arag\u00f3n), 50009 Zaragoza, Spain"},{"name":"Instituto Agroalimentario de Arag\u00f3n (IA2), 50013 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8787","DOI":"10.3748\/wjg.v21.i29.8787","article-title":"Role of the Normal Gut Microbiota","volume":"21","author":"Jandhyala","year":"2015","journal-title":"World J. 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