{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T21:11:56Z","timestamp":1793481116890,"version":"4.5.0"},"reference-count":71,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e4tsklinikum W\u00fcrzburg","id":[{"id":"https:\/\/ror.org\/03pvr2g57","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Genome Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Prolonged fasting may improve metabolic health, but controlled data in healthy adults with longer follow-up and multi-omics profiling are limited. We investigated the immediate and 12-week follow-up effects of a 5-day fasting intervention on body composition, gut microbiome, and circulating and fecal metabolites, and assessed whether baseline characteristics predict individual weight-loss response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a randomized, waitlist-controlled trial, 38 healthy adults completed a 5-day fasting intervention with 12-week follow-up (LEANER study). Outcomes included body mass index and body composition, gut microbiome composition, and plasma and fecal metabolites. Changes over time and between groups were evaluated using regression-based models and paired non-parametric tests, as appropriate. Additionally, permutation-based multivariate testing was performed on microbiome and metabolome data. Twelve-week body weight response was predicted using data-driven machine learning with cross-validation, followed by external validation in three independent cohorts undergoing prolonged fasting protocols.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fasting reduced body mass index acutely, predominantly driven by loss of fat mass, and these improvements partially persisted at 12 weeks. Fasting induced marked shifts in gut microbiome composition and in plasma and fecal metabolites. Post-fasting and longer-term changes in microbial diversity were associated with baseline microbiome diversity. A model combining baseline microbiome and clinical variables predicted body mass index response at 12 weeks; prominent predictors included an unclassified\n                      <jats:italic>Faecalibacterium<\/jats:italic>\n                      species,\n                      <jats:italic>Oscillibacter<\/jats:italic>\n                      sp. 50_27, low-density lipoprotein cholesterol, and systolic blood pressure. The model generalized to three independent cohorts, including individuals with metabolic syndrome, patients with multiple sclerosis exposed to repeated fasting, and healthy volunteers fasting for 6\u201312 days.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In healthy adults, a 5-day prolonged fasting intervention produces robust short-term metabolic changes with partial persistence and consistent remodeling of the gut microbiome and metabolite profiles. Baseline microbiome and clinical characteristics can help stratify expected longer-term responses, supporting the development of individualized fasting-based interventions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov, NCT04452916. Prospectively registered on June 29, 2020.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13073-026-01765-0","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T08:33:18Z","timestamp":1789547598000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Machine learning identifies microbiome and clinical predictors of sustained weight loss following prolonged fasting"],"prefix":"10.1186","volume":"18","author":[{"given":"Gelsomina","family":"Kaufhold","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theda U. P.","family":"Bartolomaeus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Sch\u00fctte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Till","family":"Sch\u00fctte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakshi","family":"Kamboj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"L\u00f6ber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Rahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"McParland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Braun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lajos","family":"Mark\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matanat","family":"Mammadli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Krannich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina S.","family":"Bahr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friederike","family":"Gutmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedemann","family":"Paul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quinten R.","family":"Ducarmon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Zeller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Mesnage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Wilck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alma","family":"Zernecke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Oefner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfram","family":"Gronwald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik N.","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia K.","family":"Forslund-Startceva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"B\u00e4hring","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik","family":"Bartolomaeus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadja","family":"Siebert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"1765_CR1","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1126\/science.aau2095","volume":"362","author":"A Di Francesco","year":"2018","unstructured":"Di Francesco A, Di Germanio C, Bernier M, de Cabo R. A time to fast. Science. 2018;362:770\u20135. https:\/\/doi.org\/10.1126\/science.aau2095.","journal-title":"Science"},{"key":"1765_CR2","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1038\/s41467-024-45260-9","volume":"15","author":"S Brandhorst","year":"2024","unstructured":"Brandhorst S, et al. Fasting-mimicking diet causes hepatic and blood markers changes indicating reduced biological age and disease risk. Nat Commun. 2024;15:1309. https:\/\/doi.org\/10.1038\/s41467-024-45260-9.","journal-title":"Nat Commun"},{"key":"1765_CR3","doi-asserted-by":"publisher","unstructured":"Gewecke K, et al. Long-term fasting induces a remodelling of fatty acid composition in erythrocyte membranes. Eur J Clin Invest. 2025;e14382. https:\/\/doi.org\/10.1111\/eci.14382.","DOI":"10.1111\/eci.14382"},{"key":"1765_CR4","doi-asserted-by":"publisher","first-page":"1779","DOI":"10.1016\/j.cmet.2024.06.013","volume":"36","author":"DA Koppold","year":"2024","unstructured":"Koppold DA, et al. International consensus on fasting terminology. Cell Metab. 2024;36:1779\u2013e17941774. https:\/\/doi.org\/10.1016\/j.cmet.2024.06.013.","journal-title":"Cell Metab"},{"key":"1765_CR5","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1016\/S2213-8587(19)30151-2","volume":"7","author":"WE Kraus","year":"2019","unstructured":"Kraus WE, et al. 2 years of calorie restriction and cardiometabolic risk (CALERIE): exploratory outcomes of a multicentre, phase 2, randomised controlled trial. Lancet Diabetes Endocrinol. 2019;7:673\u201383. https:\/\/doi.org\/10.1016\/S2213-8587(19)30151-2.","journal-title":"Lancet Diabetes Endocrinol"},{"key":"1765_CR6","doi-asserted-by":"publisher","first-page":"e082007","DOI":"10.1136\/bmj-2024-082007","volume":"389","author":"Z Semnani-Azad","year":"2025","unstructured":"Semnani-Azad Z, et al. Intermittent fasting strategies and their effects on body weight and other cardiometabolic risk factors: systematic review and network meta-analysis of randomised clinical trials. BMJ. 2025;389:e082007. https:\/\/doi.org\/10.1136\/bmj-2024-082007.","journal-title":"BMJ"},{"key":"1765_CR7","doi-asserted-by":"publisher","first-page":"1970","DOI":"10.1038\/s41467-021-22097-0","volume":"12","author":"A Maifeld","year":"2021","unstructured":"Maifeld A, et al. Fasting alters the gut microbiome reducing blood pressure and body weight in metabolic syndrome patients. Nat Commun. 2021;12:1970. https:\/\/doi.org\/10.1038\/s41467-021-22097-0.","journal-title":"Nat Commun"},{"key":"1765_CR8","doi-asserted-by":"publisher","first-page":"1222","DOI":"10.1016\/j.cmet.2018.05.006","volume":"27","author":"F Cignarella","year":"2018","unstructured":"Cignarella F, et al. Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota. Cell Metab. 2018;27:1222\u2013e12351226. https:\/\/doi.org\/10.1016\/j.cmet.2018.05.006.","journal-title":"Cell Metab"},{"key":"1765_CR9","doi-asserted-by":"publisher","first-page":"2136","DOI":"10.1016\/j.celrep.2016.05.009","volume":"15","author":"IY Choi","year":"2016","unstructured":"Choi IY, et al. A Diet Mimicking Fasting Promotes Regeneration and Reduces Autoimmunity and Multiple Sclerosis Symptoms. Cell Rep. 2016;15:2136\u201346. https:\/\/doi.org\/10.1016\/j.celrep.2016.05.009.","journal-title":"Cell Rep"},{"key":"1765_CR10","doi-asserted-by":"publisher","first-page":"3083","DOI":"10.1038\/s41467-020-16138-3","volume":"11","author":"S de Groot","year":"2020","unstructured":"de Groot S, et al. Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial. Nat Commun. 2020;11:3083. https:\/\/doi.org\/10.1038\/s41467-020-16138-3.","journal-title":"Nat Commun"},{"key":"1765_CR11","unstructured":"National Academies of Sciences, E. &, Medicine. Dietary Reference Intakes for Energy. National Academies; 2023."},{"key":"1765_CR12","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1038\/sj.ijo.0800910","volume":"23","author":"C Weyer","year":"1999","unstructured":"Weyer C, Snitker S, Rising R, Bogardus C, Ravussin E. Determinants of energy expenditure and fuel utilization in man: effects of body composition, age, sex, ethnicity and glucose tolerance in 916 subjects. Int J Obes Relat Metab Disord. 1999;23:715\u201322. https:\/\/doi.org\/10.1038\/sj.ijo.0800910.","journal-title":"Int J Obes Relat Metab Disord"},{"key":"1765_CR13","doi-asserted-by":"publisher","unstructured":"Delsoglio M, Achamrah N, Berger MM, Pichard C. Indirect calorimetry in clinical practice. J Clin Med. 2019;8. https:\/\/doi.org\/10.3390\/jcm8091387.","DOI":"10.3390\/jcm8091387"},{"key":"1765_CR14","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1079\/phn2005800","volume":"8","author":"JA Levine","year":"2005","unstructured":"Levine JA. Measurement of energy expenditure. Public Health Nutr. 2005;8:1123\u201332. https:\/\/doi.org\/10.1079\/phn2005800.","journal-title":"Public Health Nutr"},{"key":"1765_CR15","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1038\/s41579-023-00998-9","volume":"22","author":"K Ratiner","year":"2024","unstructured":"Ratiner K, Ciocan D, Abdeen SK, Elinav E. Utilization of the microbiome in personalized medicine. Nat Rev Microbiol. 2024;22:291\u2013308. https:\/\/doi.org\/10.1038\/s41579-023-00998-9.","journal-title":"Nat Rev Microbiol"},{"key":"1765_CR16","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1038\/s41586-021-03663-4","volume":"595","author":"RJ von Schwartzenberg","year":"2021","unstructured":"von Schwartzenberg RJ, et al. Caloric restriction disrupts the microbiota and colonization resistance. Nature. 2021;595:272\u20137. https:\/\/doi.org\/10.1038\/s41586-021-03663-4.","journal-title":"Nature"},{"key":"1765_CR17","doi-asserted-by":"publisher","first-page":"101548","DOI":"10.1016\/j.xcrm.2024.101548","volume":"5","author":"VL Murthy","year":"2024","unstructured":"Murthy VL, et al. Metabolic liability for weight gain in early adulthood. Cell Rep Med. 2024;5:101548. https:\/\/doi.org\/10.1016\/j.xcrm.2024.101548.","journal-title":"Cell Rep Med"},{"key":"1765_CR18","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1038\/s42255-025-01246-5","volume":"7","author":"Z Jiang","year":"2025","unstructured":"Jiang Z, et al. Human gut microbial aromatic amino acid and related metabolites prevent obesity through intestinal immune control. Nat Metab. 2025;7:808\u201322. https:\/\/doi.org\/10.1038\/s42255-025-01246-5.","journal-title":"Nat Metab"},{"key":"1765_CR19","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1038\/mi.2009.132","volume":"3","author":"DA Hill","year":"2010","unstructured":"Hill DA, et al. Metagenomic analyses reveal antibiotic-induced temporal and spatial changes in intestinal microbiota with associated alterations in immune cell homeostasis. Mucosal Immunol. 2010;3:148\u201358. https:\/\/doi.org\/10.1038\/mi.2009.132.","journal-title":"Mucosal Immunol"},{"key":"1765_CR20","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.cell.2004.07.002","volume":"118","author":"S Rakoff-Nahoum","year":"2004","unstructured":"Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, Edberg S, Medzhitov R. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell. 2004;118:229\u201341. https:\/\/doi.org\/10.1016\/j.cell.2004.07.002.","journal-title":"Cell"},{"key":"1765_CR21","doi-asserted-by":"publisher","first-page":"3555","DOI":"10.1038\/s41591-024-03280-4","volume":"30","author":"J Zheng","year":"2024","unstructured":"Zheng J, et al. Noninvasive, microbiome-based diagnosis of inflammatory bowel disease. Nat Med. 2024;30:3555\u201367. https:\/\/doi.org\/10.1038\/s41591-024-03280-4.","journal-title":"Nat Med"},{"key":"1765_CR22","doi-asserted-by":"publisher","first-page":"103208","DOI":"10.1016\/j.jbi.2019.103208","volume":"95","author":"PA Harris","year":"2019","unstructured":"Harris PA, et al. The REDCap consortium: Building an international community of software platform partners. J Biomed Inf. 2019;95:103208. https:\/\/doi.org\/10.1016\/j.jbi.2019.103208.","journal-title":"J Biomed Inf"},{"key":"1765_CR23","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.jbi.2008.08.010","volume":"42","author":"PA Harris","year":"2009","unstructured":"Harris PA, et al. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inf. 2009;42:377\u201381. https:\/\/doi.org\/10.1016\/j.jbi.2008.08.010.","journal-title":"J Biomed Inf"},{"key":"1765_CR24","doi-asserted-by":"publisher","first-page":"e081123","DOI":"10.1136\/bmj-2024-081123","volume":"389","author":"S Hopewell","year":"2025","unstructured":"Hopewell S, et al. CONSORT 2025 statement: updated guideline for reporting randomised trials. BMJ. 2025;389:e081123. https:\/\/doi.org\/10.1136\/bmj-2024-081123.","journal-title":"BMJ"},{"key":"1765_CR25","doi-asserted-by":"publisher","unstructured":"Mahler A, et al. Increased salt intake decreases diet-induced thermogenesis in healthy volunteers: a randomized placebo-controlled study. Nutrients. 2022;14. https:\/\/doi.org\/10.3390\/nu14020253.","DOI":"10.3390\/nu14020253"},{"key":"1765_CR26","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1186\/s40795-025-01156-5","volume":"11","author":"LS Bahr","year":"2025","unstructured":"Bahr LS, et al. Fasting, ketogenic, and anti-inflammatory diets in multiple sclerosis: a randomized controlled trial with 18-month follow-up. BMC Nutr. 2025;11:167. https:\/\/doi.org\/10.1186\/s40795-025-01156-5.","journal-title":"BMC Nutr"},{"key":"1765_CR27","doi-asserted-by":"publisher","unstructured":"Ducarmon Q et al. Long-term fasting remodels gut microbial metabolism and host metabolism. bioRxiv. 2024;2024.04.19.590209. https:\/\/doi.org\/10.1101\/2024.04.19.590209.","DOI":"10.1101\/2024.04.19.590209"},{"key":"1765_CR28","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1093\/cvr\/cvaa128","volume":"117","author":"TUP Bartolomaeus","year":"2021","unstructured":"Bartolomaeus TUP, et al. Quantifying technical confounders in microbiome studies. Cardiovasc Res. 2021;117:863\u201375. https:\/\/doi.org\/10.1093\/cvr\/cvaa128.","journal-title":"Cardiovasc Res"},{"key":"1765_CR29","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1038\/ismej.2015.188","volume":"10","author":"Y Darzi","year":"2016","unstructured":"Darzi Y, Falony G, Vieira-Silva S, Raes J. Towards biome-specific analysis of meta-omics data. ISME J. 2016;10:1025\u20138. https:\/\/doi.org\/10.1038\/ismej.2015.188.","journal-title":"ISME J"},{"key":"1765_CR30","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1515\/cclm-2013-0249","volume":"51","author":"Y Ozarda","year":"2013","unstructured":"Ozarda Y, et al. Protocol and standard operating procedures for common use in a worldwide multicenter study on reference values. Clin Chem Lab Med. 2013;51:1027\u201340. https:\/\/doi.org\/10.1515\/cclm-2013-0249.","journal-title":"Clin Chem Lab Med"},{"key":"1765_CR31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v028.i08","volume":"28","author":"T Hothorn","year":"2008","unstructured":"Hothorn T, Hornik K, van de Wiel MA, Zeileis A. Implementing a Class of Permutation Tests: The coin Package. J Stat Softw. 2008;28:1\u201323. https:\/\/doi.org\/10.18637\/jss.v028.i08.","journal-title":"J Stat Softw"},{"key":"1765_CR32","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1007\/s11357-020-00156-6","volume":"42","author":"CR Martens","year":"2020","unstructured":"Martens CR, et al. Short-term time-restricted feeding is safe and feasible in non-obese healthy midlife and older adults. Geroscience. 2020;42:667\u201386. https:\/\/doi.org\/10.1007\/s11357-020-00156-6.","journal-title":"Geroscience"},{"key":"1765_CR33","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/s41430-021-00909-2","volume":"76","author":"Y Gao","year":"2022","unstructured":"Gao Y, Tsintzas K, Macdonald IA, Cordon SM, Taylor MA. Effects of intermittent (5:2) or continuous energy restriction on basal and postprandial metabolism: a randomised study in normal-weight, young participants. Eur J Clin Nutr. 2022;76:65\u201373. https:\/\/doi.org\/10.1038\/s41430-021-00909-2.","journal-title":"Eur J Clin Nutr"},{"key":"1765_CR34","doi-asserted-by":"publisher","first-page":"1871","DOI":"10.1016\/j.clnu.2017.11.018","volume":"37","author":"JF Trepanowski","year":"2018","unstructured":"Trepanowski JF, et al. Effects of alternate-day fasting or daily calorie restriction on body composition, fat distribution, and circulating adipokines: Secondary analysis of a randomized controlled trial. Clin Nutr. 2018;37:1871\u20138. https:\/\/doi.org\/10.1016\/j.clnu.2017.11.018.","journal-title":"Clin Nutr"},{"key":"1765_CR35","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1186\/s12967-018-1748-4","volume":"16","author":"I Cioffi","year":"2018","unstructured":"Cioffi I, et al. Intermittent versus continuous energy restriction on weight loss and cardiometabolic outcomes: a systematic review and meta-analysis of randomized controlled trials. J Transl Med. 2018;16:371. https:\/\/doi.org\/10.1186\/s12967-018-1748-4.","journal-title":"J Transl Med"},{"key":"1765_CR36","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1055\/s-0043-101700","volume":"125","author":"C Li","year":"2017","unstructured":"Li C, et al. Effects of A One-week Fasting Therapy in Patients with Type-2 Diabetes Mellitus and Metabolic Syndrome - A Randomized Controlled Explorative Study. Exp Clin Endocrinol Diabetes. 2017;125:618\u201324. https:\/\/doi.org\/10.1055\/s-0043-101700.","journal-title":"Exp Clin Endocrinol Diabetes"},{"key":"1765_CR37","doi-asserted-by":"publisher","first-page":"e0209353","DOI":"10.1371\/journal.pone.0209353","volume":"14","author":"F Wilhelmi de Toledo","year":"2019","unstructured":"Wilhelmi de Toledo F, Grundler F, Bergouignan A, Drinda S, Michalsen A. Safety, health improvement and well-being during a 4 to 21-day fasting period in an observational study including 1422 subjects. PLoS ONE. 2019;14:e0209353. https:\/\/doi.org\/10.1371\/journal.pone.0209353.","journal-title":"PLoS ONE"},{"key":"1765_CR38","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1159\/000357875","volume":"20","author":"R Stange","year":"2013","unstructured":"Stange R, Pflugbeil C, Michalsen A, Uehleke B. Therapeutic fasting in patients with metabolic syndrome and impaired insulin resistance. Forsch Komplementmed. 2013;20:421\u20136. https:\/\/doi.org\/10.1159\/000357875.","journal-title":"Forsch Komplementmed"},{"key":"1765_CR39","doi-asserted-by":"publisher","first-page":"1690","DOI":"10.1002\/jcsm.12766","volume":"12","author":"C Laurens","year":"2021","unstructured":"Laurens C, et al. Is muscle and protein loss relevant in long-term fasting in healthy men? A prospective trial on physiological adaptations. J Cachexia Sarcopenia Muscle. 2021;12:1690\u2013703. https:\/\/doi.org\/10.1002\/jcsm.12766.","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"1765_CR40","doi-asserted-by":"publisher","unstructured":"Dai Z, et al. Effects of 10-day complete fasting on physiological homeostasis, nutrition and health markers in male adults. Nutrients. 2022;14. https:\/\/doi.org\/10.3390\/nu14183860.","DOI":"10.3390\/nu14183860"},{"key":"1765_CR41","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1590\/1415-52732015000500005","volume":"28","author":"AT Triffoni-Melo","year":"2015","unstructured":"Triffoni-Melo AT, Suen VMM, Resende CMM, Braga CBM, Diez-Garcia RW. Resting energy expenditure adaptation after short-term caloric restriction in morbidly obese women. Rev Nutr. 2015;28:505\u201311. https:\/\/doi.org\/10.1590\/1415-52732015000500005.","journal-title":"Rev Nutr"},{"key":"1765_CR42","doi-asserted-by":"publisher","first-page":"3680","DOI":"10.2337\/db15-0382","volume":"64","author":"M Schlogl","year":"2015","unstructured":"Schlogl M, et al. Energy Expenditure Responses to Fasting and Overfeeding Identify Phenotypes Associated With Weight Change. Diabetes. 2015;64:3680\u20139. https:\/\/doi.org\/10.2337\/db15-0382.","journal-title":"Diabetes"},{"key":"1765_CR43","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1152\/jappl.2001.90.1.155","volume":"90","author":"TJ Horton","year":"2001","unstructured":"Horton TJ, Hill JO. Prolonged fasting significantly changes nutrient oxidation and glucose tolerance after a normal mixed meal. J Appl Physiol (1985). 2001;90:155\u201363. https:\/\/doi.org\/10.1152\/jappl.2001.90.1.155.","journal-title":"J Appl Physiol (1985)"},{"key":"1765_CR44","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1017\/S0007114523000557","volume":"130","author":"R Solianik","year":"2023","unstructured":"Solianik R, Zidoniene K, Eimantas N, Brazaitis M. Prolonged fasting outperforms short-term fasting in terms of glucose tolerance and insulin release: a randomised controlled trial. Br J Nutr. 2023;130:1500\u20139. https:\/\/doi.org\/10.1017\/S0007114523000557.","journal-title":"Br J Nutr"},{"key":"1765_CR45","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1038\/s41591-020-0934-0","volume":"26","author":"SE Berry","year":"2020","unstructured":"Berry SE, et al. Human postprandial responses to food and potential for precision nutrition. Nat Med. 2020;26:964\u201373. https:\/\/doi.org\/10.1038\/s41591-020-0934-0.","journal-title":"Nat Med"},{"key":"1765_CR46","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1016\/j.cell.2015.11.001","volume":"163","author":"D Zeevi","year":"2015","unstructured":"Zeevi D, et al. Personalized Nutrition by Prediction of Glycemic Responses. Cell. 2015;163:1079\u201394. https:\/\/doi.org\/10.1016\/j.cell.2015.11.001.","journal-title":"Cell"},{"key":"1765_CR47","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1038\/s41366-018-0093-2","volume":"43","author":"MF Hjorth","year":"2019","unstructured":"Hjorth MF, et al. Prevotella-to-Bacteroides ratio predicts body weight and fat loss success on 24-week diets varying in macronutrient composition and dietary fiber: results from a post-hoc analysis. Int J Obes (Lond). 2019;43:149\u201357. https:\/\/doi.org\/10.1038\/s41366-018-0093-2.","journal-title":"Int J Obes (Lond)"},{"key":"1765_CR48","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1038\/s41598-020-58000-y","volume":"10","author":"JA Grembi","year":"2020","unstructured":"Grembi JA, et al. Gut microbiota plasticity is correlated with sustained weight loss on a low-carb or low-fat dietary intervention. Sci Rep. 2020;10:1405. https:\/\/doi.org\/10.1038\/s41598-020-58000-y.","journal-title":"Sci Rep"},{"key":"1765_CR49","doi-asserted-by":"publisher","first-page":"e0096421","DOI":"10.1128\/mSystems.00964-21","volume":"6","author":"C Diener","year":"2021","unstructured":"Diener C, et al. Baseline Gut Metagenomic Functional Gene Signature Associated with Variable Weight Loss Responses following a Healthy Lifestyle Intervention in Humans. mSystems. 2021;6:e0096421. https:\/\/doi.org\/10.1128\/mSystems.00964-21.","journal-title":"mSystems"},{"key":"1765_CR50","doi-asserted-by":"publisher","first-page":"718661","DOI":"10.3389\/fnut.2021.718661","volume":"8","author":"TS Dong","year":"2021","unstructured":"Dong TS, et al. The Intestinal Microbiome Predicts Weight Loss on a Calorie-Restricted Diet and Is Associated With Improved Hepatic Steatosis. Front Nutr. 2021;8:718661. https:\/\/doi.org\/10.3389\/fnut.2021.718661.","journal-title":"Front Nutr"},{"key":"1765_CR51","doi-asserted-by":"publisher","first-page":"4155","DOI":"10.1038\/s41467-024-48355-5","volume":"15","author":"AE Mohr","year":"2024","unstructured":"Mohr AE, et al. Gut microbiome remodeling and metabolomic profile improves in response to protein pacing with intermittent fasting versus continuous caloric restriction. Nat Commun. 2024;15:4155. https:\/\/doi.org\/10.1038\/s41467-024-48355-5.","journal-title":"Nat Commun"},{"key":"1765_CR52","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1161\/CIRCRESAHA.123.322381","volume":"134","author":"YC Wang","year":"2024","unstructured":"Wang YC, et al. Indole-3-Propionic Acid Protects Against Heart Failure With Preserved Ejection Fraction. Circ Res. 2024;134:371\u201389. https:\/\/doi.org\/10.1161\/CIRCRESAHA.123.322381.","journal-title":"Circ Res"},{"key":"1765_CR53","doi-asserted-by":"publisher","first-page":"1654","DOI":"10.1128\/AEM.66.4.1654-1661.2000","volume":"66","author":"A Barcenilla","year":"2000","unstructured":"Barcenilla A, et al. Phylogenetic relationships of butyrate-producing bacteria from the human gut. Appl Environ Microbiol. 2000;66:1654\u201361. https:\/\/doi.org\/10.1128\/AEM.66.4.1654-1661.2000.","journal-title":"Appl Environ Microbiol"},{"key":"1765_CR54","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1038\/s41522-024-00538-0","volume":"10","author":"M Essex","year":"2024","unstructured":"Essex M, et al. Gut microbiota dysbiosis is associated with altered tryptophan metabolism and dysregulated inflammatory response in COVID-19. NPJ Biofilms Microbiomes. 2024;10:66. https:\/\/doi.org\/10.1038\/s41522-024-00538-0.","journal-title":"NPJ Biofilms Microbiomes"},{"key":"1765_CR55","doi-asserted-by":"publisher","first-page":"3294","DOI":"10.1038\/s41467-018-05470-4","volume":"9","author":"HM Roager","year":"2018","unstructured":"Roager HM, Licht TR. Microbial tryptophan catabolites in health and disease. Nat Commun. 2018;9:3294. https:\/\/doi.org\/10.1038\/s41467-018-05470-4.","journal-title":"Nat Commun"},{"key":"1765_CR56","doi-asserted-by":"publisher","first-page":"100897","DOI":"10.1016\/j.xcrm.2022.100897","volume":"4","author":"R Hanssen","year":"2023","unstructured":"Hanssen R, et al. Circulating uridine dynamically and adaptively regulates food intake in humans. Cell Rep Med. 2023;4:100897. https:\/\/doi.org\/10.1016\/j.xcrm.2022.100897.","journal-title":"Cell Rep Med"},{"key":"1765_CR57","doi-asserted-by":"publisher","unstructured":"Deng Y, et al. An adipo-biliary-uridine axis that regulates energy homeostasis. Science. 2017;355. https:\/\/doi.org\/10.1126\/science.aaf5375.","DOI":"10.1126\/science.aaf5375"},{"key":"1765_CR58","doi-asserted-by":"publisher","first-page":"1404","DOI":"10.1016\/j.cell.2015.08.032","volume":"162","author":"SM Steculorum","year":"2015","unstructured":"Steculorum SM, et al. Hypothalamic UDP Increases in Obesity and Promotes Feeding via P2Y6-Dependent Activation of AgRP Neurons. Cell. 2015;162:1404\u201317. https:\/\/doi.org\/10.1016\/j.cell.2015.08.032.","journal-title":"Cell"},{"key":"1765_CR59","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.molmet.2018.02.013","volume":"11","author":"Y Deng","year":"2018","unstructured":"Deng Y, et al. Adipocyte Xbp1s overexpression drives uridine production and reduces obesity. Mol Metab. 2018;11:1\u201317. https:\/\/doi.org\/10.1016\/j.molmet.2018.02.013.","journal-title":"Mol Metab"},{"key":"1765_CR60","doi-asserted-by":"publisher","first-page":"642999","DOI":"10.3389\/fmicb.2021.642999","volume":"12","author":"I Ali","year":"2021","unstructured":"Ali I, et al. Ramadan Fasting Leads to Shifts in Human Gut Microbiota Structured by Dietary Composition. Front Microbiol. 2021;12:642999. https:\/\/doi.org\/10.3389\/fmicb.2021.642999.","journal-title":"Front Microbiol"},{"key":"1765_CR61","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1038\/ismej.2016.176","volume":"11","author":"M Lopez-Siles","year":"2017","unstructured":"Lopez-Siles M, Duncan SH, Garcia-Gil LJ, Martinez-Medina M. Faecalibacterium prausnitzii: from microbiology to diagnostics and prognostics. ISME J. 2017;11:841\u201352. https:\/\/doi.org\/10.1038\/ismej.2016.176.","journal-title":"ISME J"},{"key":"1765_CR62","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1007\/s00508-015-0755-1","volume":"127","author":"M Remely","year":"2015","unstructured":"Remely M, et al. Increased gut microbiota diversity and abundance of Faecalibacterium prausnitzii and Akkermansia after fasting: a pilot study. Wien Klin Wochenschr. 2015;127:394\u20138. https:\/\/doi.org\/10.1007\/s00508-015-0755-1.","journal-title":"Wien Klin Wochenschr"},{"key":"1765_CR63","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1210\/clinem\/dgaa644","volume":"106","author":"Y Guo","year":"2021","unstructured":"Guo Y, et al. Intermittent Fasting Improves Cardiometabolic Risk Factors and Alters Gut Microbiota in Metabolic Syndrome Patients. J Clin Endocrinol Metab. 2021;106:64\u201379. https:\/\/doi.org\/10.1210\/clinem\/dgaa644.","journal-title":"J Clin Endocrinol Metab"},{"key":"1765_CR64","doi-asserted-by":"publisher","first-page":"e36","DOI":"10.1017\/jns.2019.33","volume":"8","author":"R Mesnage","year":"2019","unstructured":"Mesnage R, Grundler F, Schwiertz A, Le Maho Y, de Wilhelmi F. Changes in human gut microbiota composition are linked to the energy metabolic switch during 10 d of Buchinger fasting. J Nutr Sci. 2019;8:e36. https:\/\/doi.org\/10.1017\/jns.2019.33.","journal-title":"J Nutr Sci"},{"key":"1765_CR65","doi-asserted-by":"publisher","first-page":"227","DOI":"10.3920\/BM2019.0039","volume":"11","author":"C Ozkul","year":"2020","unstructured":"Ozkul C, Yalinay M, Karakan T. Structural changes in gut microbiome after Ramadan fasting: a pilot study. Benef Microbes. 2020;11:227\u201333. https:\/\/doi.org\/10.3920\/BM2019.0039.","journal-title":"Benef Microbes"},{"key":"1765_CR66","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1136\/gutjnl-2020-321747","volume":"70","author":"M Fassarella","year":"2021","unstructured":"Fassarella M, et al. Gut microbiome stability and resilience: elucidating the response to perturbations in order to modulate gut health. Gut. 2021;70:595\u2013605. https:\/\/doi.org\/10.1136\/gutjnl-2020-321747.","journal-title":"Gut"},{"key":"1765_CR67","doi-asserted-by":"publisher","first-page":"922727","DOI":"10.3389\/fmicb.2022.922727","volume":"13","author":"MN Khan","year":"2022","unstructured":"Khan MN, et al. Intermittent fasting positively modulates human gut microbial diversity and ameliorates blood lipid profile. Front Microbiol. 2022;13:922727. https:\/\/doi.org\/10.3389\/fmicb.2022.922727.","journal-title":"Front Microbiol"},{"key":"1765_CR68","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/s12859-023-05156-9","volume":"24","author":"D Rajput","year":"2023","unstructured":"Rajput D, Wang WJ, Chen CC. Evaluation of a decided sample size in machine learning applications. BMC Bioinformatics. 2023;24:48. https:\/\/doi.org\/10.1186\/s12859-023-05156-9.","journal-title":"BMC Bioinformatics"},{"key":"1765_CR69","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1007\/s13167-020-00216-z","volume":"11","author":"C Birkenbihl","year":"2020","unstructured":"Birkenbihl C, et al. Differences in cohort study data affect external validation of artificial intelligence models for predictive diagnostics of dementia - lessons for translation into clinical practice. EPMA J. 2020;11:367\u201376. https:\/\/doi.org\/10.1007\/s13167-020-00216-z.","journal-title":"EPMA J"},{"key":"1765_CR70","doi-asserted-by":"publisher","DOI":"10.5281\/zenodo.17493808","author":"GN Kaufhold","year":"2025","unstructured":"Kaufhold GN, Bartolomaeus TUP, Bartolomaeus H. Machine Learning Identifies Microbiome and Clinical Predictors of Sustained Weight Loss Following Prolonged Fasting. Zenodo. 2025. https:\/\/doi.org\/10.5281\/zenodo.17493808.","journal-title":"Zenodo"},{"key":"1765_CR71","unstructured":"PRJNA1293883. NIH Sequence Read Archive. 2026. https:\/\/www.ncbi.nlm.nih.gov\/bioproject\/PRJNA1293883"}],"container-title":["Genome Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13073-026-01765-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13073-026-01765-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13073-026-01765-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T12:47:14Z","timestamp":1789649234000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13073-026-01765-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":71,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1765"],"URL":"https:\/\/doi.org\/10.1186\/s13073-026-01765-0","relation":{},"ISSN":["1756-994X"],"issn-type":[{"value":"1756-994X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,16]]},"assertion":[{"value":"6 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 September 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 September 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study protocol was approved by the institutional review board of Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin (EA1\/033\/20). The study was conducted in accordance with the principles of the Declaration of Helsinki. All participants provided written informed consent before entering the study.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Patients provided written informed consent for the publication of anonymized data.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"NS has received speaker honoraria from Teva GmbH, Alexion Pharma Germany GmbH and Roche Pharma AG. RM is employed by the Buchinger Wilhelmi Development & Holding GmbH. The other authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"136"}}