{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T19:12:40Z","timestamp":1793041960391,"version":"4.5.0"},"reference-count":48,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021821","name":"Oncode Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100021821","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/01n92vv28","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Fasting-mimicking diets (FMDs) induce metabolic changes associated with immunomodulation in preclinical studies, yet little is known about the effects of FMD on the human circulating immune system. Methods: In the single-arm FIND pilot study (NCT04833439), six of nine healthy participants completed two cycles of a 4-day FMD separated by 3 weeks of regular diet in a repeated-measures design. Blood samples were collected at baseline, after an overnight fast, and the morning after completion of the second FMD cycle. Peripheral blood mononuclear cells (PBMCs) were analyzed by transcriptomic profiling and spectral flow cytometry. Results: FMD was associated with reduced plasma glucose and insulin-like growth factor-1 and increased ketone levels. Transcriptomic analysis showed increased expression of genes involved in the TNF\u03b1, IFN\u03b3 and IFN\u03b1 signaling pathway after two FMD cycles. Fifteen of the 39 leading-edge genes of the TNF\u03b1 signature that have previously been associated with myeloid activity and rapid stress responses corresponded with the increased frequencies of circulating CD14-CD11b-CD11c+ dendritic cells (DCs), CD123+ plasmacytoid DCs, and CD14+ CD16+ intermediate monocytes. Moreover, the frequencies of HLA-DR-expressing CD4+ and CD8+ T-cells increased (p &lt; 0.05) after two FMD cycles. Conclusions: In healthy volunteers, two cycles of FMD were associated with metabolic changes and alterations in circulating myeloid and T-cell populations consistent with activation of selected inflammatory pathways. These exploratory findings warrant larger validation studies in healthy volunteers in combination with functional analyses.<\/jats:p>","DOI":"10.3390\/nu18152514","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T10:24:07Z","timestamp":1785752647000},"page":"2514","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploring the Immunomodulatory Effects of Fasting-Mimicking Diet in Healthy Individuals: A Pilot Study"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0609-7814","authenticated-orcid":false,"given":"Nadia","family":"de Gruil","sequence":"first","affiliation":[{"name":"Medical Oncology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9809-8266","authenticated-orcid":false,"given":"Marij J. P.","family":"Welters","sequence":"additional","affiliation":[{"name":"Experimental Cancer Immunology and Therapy Group, Medical Oncology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2874-4402","authenticated-orcid":false,"given":"Saskia J.","family":"Santegoets","sequence":"additional","affiliation":[{"name":"Experimental Cancer Immunology and Therapy Group, Medical Oncology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2191-7689","authenticated-orcid":false,"given":"Sanne","family":"Boekestijn","sequence":"additional","affiliation":[{"name":"Experimental Cancer Immunology and Therapy Group, Medical Oncology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Kaart","sequence":"additional","affiliation":[{"name":"Medical Oncology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3076-1551","authenticated-orcid":false,"given":"Hanno","family":"Pijl","sequence":"additional","affiliation":[{"name":"Internal Medicine Endocrinology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2671-1903","authenticated-orcid":false,"given":"Judith R.","family":"Kroep","sequence":"additional","affiliation":[{"name":"Medical Oncology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6556-0354","authenticated-orcid":false,"given":"Sjoerd H.","family":"van der Burg","sequence":"additional","affiliation":[{"name":"Experimental Cancer Immunology and Therapy Group, Medical Oncology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"},{"name":"Oncode Institute, 3521 AL Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.cmet.2015.05.012","article-title":"A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan","volume":"22","author":"Brandhorst","year":"2015","journal-title":"Cell Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1038\/s41568-018-0061-0","article-title":"Fasting and cancer: Molecular mechanisms and clinical application","volume":"18","author":"Nencioni","year":"2018","journal-title":"Nat. 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