{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:23:00Z","timestamp":1785424980593,"version":"3.56.0"},"reference-count":20,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Rehabilitation Medicine, Hannover Medical School"},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/018mejw64","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001652","name":"FAU Erlangen-N\u00fcrnberg","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001652","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/00f7hpc57","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Hector Stiftung II and the Medical Research Foundation at Erlangen University Hospital"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Prolonged intermittent fasting is associated with metabolic and immune adaptation; however, the extent to which transcriptional immune responses translate into systemic inflammatory changes, and how these processes relate to autophagy, senescence-associated signaling, and inflammasome regulation, remains incompletely understood. Methods: This study represents a secondary integrative analysis of a previously characterized cohort of healthy young men undergoing Ramadan fasting. Longitudinal data across four time points (T1\u2013T4) were re-analyzed, integrating targeted mRNA profiling of autophagy-, senescence-, and inflammasome-related genes with circulating cytokines and clinical parameters. Baseline-stratified regression and exploratory clustering were applied to assess inter-individual variability. Results: Fasting was associated with modest reductions in body weight (\u22121.78 \u00b1 1.44 kg, FDR &lt; 0.001) and BMI (\u22120.56 \u00b1 0.47 kg\/m2, FDR &lt; 0.001), without hemodynamic instability. Autophagy-related transcripts (ULK1, ATG5) were upregulated, while senescence markers showed divergent regulation (p53\u2191, p21\u2193). Inflammasome-related genes (NLRP3, IL1B) increased at the transcriptional level; however, circulating IL-1\u03b2 and IL-6 remained stable and TNF\u03b1 decreased (FDR &lt; 0.001), indicating dissociation between transcriptional priming and systemic cytokine output. \u0394NLRP3 was inversely associated with baseline expression (\u03b2 = \u22121.88, R2 = 0.31, p = 0.0056), suggesting baseline-dependent transcriptional responsiveness. Responses followed a continuous spectrum rather than discrete subtypes. Conclusions: Prolonged intermittent fasting is associated with coordinated immunometabolic remodeling characterized by transcriptional changes in autophagy-, senescence-, and inflammasome-related pathways, without systemic inflammatory escalation. Inflammasome-related responses appear baseline-dependent, suggesting graded immunological responsiveness rather than a uniform activation. These findings are hypothesis-generating and support the interpretation of fasting as a graded immunometabolic modulator rather than a uniform pro-inflammatory stimulus within the limitations of a secondary exploratory analysis.<\/jats:p>","DOI":"10.3390\/nu18121954","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T10:19:53Z","timestamp":1781691593000},"page":"1954","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Baseline-Dependent Immunometabolic Responses During Prolonged Intermittent Fasting: A Secondary Integrative Analysis"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5019-3387","authenticated-orcid":false,"given":"Zulrahman","family":"Erlangga","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Krankenhaus Winsen, 21423 Winsen, Germany"},{"name":"Department of Kidney, Liver and Metabolic Diseases, Children Hospital, Medizinische Hochschule Hannover, 30625 Hanover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samaneh","family":"Souita","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Johannes Wesling Medical Centre, 32429 Minden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imad","family":"Hamdan","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation and Sport Medicine, Medizinische Hochschule Hannover, 30625 Hanover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3432-7488","authenticated-orcid":false,"given":"Yurdag\u00fcl","family":"Zopf","sequence":"additional","affiliation":[{"name":"Department of Medicine 1\u2013Gastroenterology, Pneumology and Endocrinology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"},{"name":"Hector-Center for Nutrition, Exercise and Sports, Friedrich-Alexander University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"},{"name":"Deutsches Zentrum Immuntherapie, University Hospital Erlangen, Friedrich-Alexander University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6522-1942","authenticated-orcid":false,"given":"Christoph","family":"Gutenbrunner","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation and Sport Medicine, Medizinische Hochschule Hannover, 30625 Hanover, Germany"},{"name":"Hannover Rehabilitation Service & Science Consulting, 30655 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1114-8444","authenticated-orcid":false,"given":"Abdulhadi","family":"Suwandi","sequence":"additional","affiliation":[{"name":"Department of Medicine 1\u2013Gastroenterology, Pneumology and Endocrinology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"},{"name":"Hector-Center for Nutrition, Exercise and Sports, Friedrich-Alexander University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5547-3169","authenticated-orcid":false,"given":"Boya","family":"Nugraha","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation and Sport Medicine, Medizinische Hochschule Hannover, 30625 Hanover, Germany"},{"name":"Hannover Rehabilitation Service & Science Consulting, 30655 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.clnesp.2025.03.006","article-title":"Cardiometabolic and Obesity Risk Outcomes of Dawn-to-Dusk, Dry Intermittent Fasting: Insights from an Umbrella Review","volume":"67","author":"Faris","year":"2025","journal-title":"Clin. 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