Fecal melatonin as a biomarker of emerging circadian maturity and gut microbiota in infancy

Fecal melatonin as a biomarker of emerging circadian maturity and gut microbiota in infancy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Fecal melatonin as a biomarker of emerging circadian maturity and gut microbiota in infancy Salome Kurth, Mohammed Al-Andoli, Petra Zimmermann, Sarah Schoch, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6569729/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Melatonin plays a key role in circadian regulation, and its interaction with the gut microbiota may be critical for early-life development. Beyond its circadian function, melatonin dysregulation is implicated in inflammatory, metabolic, psychiatric, and neurological disorders. While the gastrointestinal tract produces melatonin at levels far exceeding the pineal gland, its role in gut microbiota dynamics and circadian maturation remains unclear. This study investigates the association between fecal melatonin levels and microbial diversity, specific bacterial taxa (ZOTUs), actimetry-based sleep metrics, and various time-dependent factors (including stool timing and intervals since the last stool, sleep, and meal) in infants at 3, 6, and 12 months of age. Key findings include: (1) fecal melatonin levels increase with age but show high inter-individual variability; (2) fecal melatonin is associated with time factors, such as stool timing and time since last stool; (3) higher fecal melatonin levels are linked with reduced gut microbial richness and diversity; (4) the number of bacterial taxa associated with fecal melatonin decline over time; (5) melatonin is associated with age-dependent shifts in both bacterial phyla and genera, notably increasing phyla Actinobacteriota and Bacteroidota, and genera Bifidobacterium, and Veillonella, while reducing the phylum Firmicutes and the genus Streptococcus; (6) fecal melatonin is linked to circadian maturation; and (7) finally, stool timing variability and fasting time affect fecal melatonin stability. These findings identify intestinal melatonin as a promising biomarker for gut microbiota development and circadian rhythm establishment. In addition, these insights highlight melatonin in infant stool as a biomarker and potential modulator bridging systems of intestinal microbiota and behavioral sleep-wake organisation. Biological sciences/Physiology Health sciences/Gastroenterology Health sciences/Biomarkers Biological sciences/Developmental biology N-acetyl-5-methoxytryptamine 5-MT clock genes actigraphy early childhood metabolism dynamic bowel temporal feeding pattern Full Text Additional Declarations Funding: This research was supported by the Swiss National Science Foundation (PCEFP1-181279 to SK; P0ZHP1-178697 to SS) and by the University of Zurich through the Faculty of Medicine, the Clinical Research Priority Program “Sleep and Health”, and the Forschungskredit (FK-18-047). Additional support was provided by the University of Zurich’s Foundation for Research in Science and the Humanities (FK-18-047 to SK) and the Olga Mayenfisch Foundation (to SK). Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6569729","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":450566865,"identity":"757a8340-eb0f-4c4d-b1ba-2c9053cbcdcf","order_by":0,"name":"Salome 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Beyond its circadian function, melatonin dysregulation is implicated in inflammatory, metabolic, psychiatric, and neurological disorders. While the gastrointestinal tract produces melatonin at levels far exceeding the pineal gland, its role in gut microbiota dynamics and circadian maturation remains unclear. This study investigates the association between fecal melatonin levels and microbial diversity, specific bacterial taxa (ZOTUs), actimetry-based sleep metrics, and various time-dependent factors (including stool timing and intervals since the last stool, sleep, and meal) in infants at 3, 6, and 12 months of age. 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