{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T18:28:37Z","timestamp":1793039317932,"version":"4.5.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:p>Functional constipation (FC) is a highly prevalent gastrointestinal disorder globally. Its complex and multidimensional pathophysiological mechanisms and the limitations of conventional treatments highlight the urgent need to explore new theoretical frameworks. Chronobiological research reveals that the circadian rhythm system plays a central role in maintaining physiological homeostasis, and rhythm disruption caused by modern lifestyles is becoming a common driving factor for various chronic diseases. The gut microbiota, as a key regulator of host physiology, its intrinsic rhythmicity and synchronization with the host\u2019s biological clock are crucial for gut health. This review systematically integrates cross-disciplinary evidence from chronobiology, microbiology, and gastrointestinal motility. Based on this evidence, we propose and substantiate the Chrono-Microbiota-Motility axis as a novel theoretical framework. This framework unveils a novel pathogenic mechanism: gut jet lag. This term describes a state of desynchronization between host and gut microbiota rhythms. This desynchronization is caused by modern lifestyle factors such as irregular routines, disordered eating times, and nocturnal light exposure. This desynchronization translates into gut dysfunction through three core pathways: disrupted short-chain fatty acid production rhythm weakens intestinal propulsive motility, dysregulation of the intrinsic gut clock inhibits morning high-amplitude contractions, and impaired intestinal barrier function triggers low-grade inflammation and increased sensitivity. Based on this theoretical framework, this paper systematically elucidates the scientific basis of \u201cchronotherapy\u201d as a non-pharmacological intervention strategy, including multi-dimensional synergistic interventions such as time-restricted eating, regular routines, light management, and individualized supplement application. This theory achieves a paradigm shift in the etiological research of FC from material homeostasis to temporal synchronization, providing a new explanatory framework for refractory cases, opening up fundamental treatment pathways, and offering evidence-based guidance for the formulation of modern lifestyle health guidelines. Incorporating the time dimension into FC research and clinical practice represents a key breakthrough in understanding this complex disease. Furthermore, it reflects modern medicine\u2019s shift toward a systemic, individualized, and preventive approach.<\/jats:p>","DOI":"10.3389\/fnut.2025.1678482","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T05:35:21Z","timestamp":1759383321000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Gut jet lag: how circadian rhythm disruption undermines the Chrono-Microbiota-Motility axis and induces functional constipation"],"prefix":"10.3389","volume":"12","author":[{"given":"Jitong","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keying","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodan","family":"Sui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Houbo","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Leng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiejun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,2]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1016\/S2468-1253(21)00111-4","article-title":"Global prevalence of functional constipation according to the Rome criteria: a systematic review and meta-analysis","volume":"6","author":"Barberio","year":"2021","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1436","DOI":"10.1111\/j.1572-0241.2007.01199.x","article-title":"A randomized, multicenter, placebo-controlled trial of polyethylene glycol laxative for chronic treatment of chronic constipation","volume":"102","author":"Dipalma","year":"2007","journal-title":"Am J Gastroenterol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"4453","DOI":"10.1073\/pnas.0808180106","article-title":"Adverse metabolic and cardiovascular consequences of circadian misalignment","volume":"106","author":"Scheer","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1495","DOI":"10.1016\/j.cell.2016.11.003","article-title":"Microbiota diurnal rhythmicity programs host transcriptome oscillations","volume":"167","author":"Thaiss","year":"2016","journal-title":"Cell"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1016\/j.cell.2014.09.048","article-title":"Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis","volume":"159","author":"Thaiss","year":"2014","journal-title":"Cell"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"198","DOI":"10.3389\/fphys.2018.00198","article-title":"Intestinal metagenomes and metabolomes in healthy young males: inactivity and hypoxia generated negative physiological symptoms precede microbial Dysbiosis","volume":"9","author":"\u0160ket","year":"2018","journal-title":"Front Physiol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"e3001865","DOI":"10.1371\/journal.pbio.3001865","article-title":"Host circadian behaviors exert only weak selective pressure on the gut microbiome under stable conditions but are critical for recovery from antibiotic treatment","volume":"20","author":"Zhao","year":"2022","journal-title":"PLoS Biol"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"109121","DOI":"10.1016\/j.jnutbio.2022.109121","article-title":"Daytime restricted feeding promotes circadian desynchrony and metabolic disruption with changes in bile acids profiles and gut microbiota in C57BL\/6 male mice","volume":"109","author":"Cui","year":"2022","journal-title":"J Nutr Biochem"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.trsl.2020.11.007","article-title":"Abnormal food timing and predisposition to weight gain: role of barrier dysfunction and microbiota","volume":"231","author":"Bishehsari","year":"2021","journal-title":"Transl Res"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1428","DOI":"10.1126\/science.aaw3134","article-title":"The intestinal microbiota programs diurnal rhythms in host metabolism through histone deacetylase 3","volume":"365","author":"Kuang","year":"2019","journal-title":"Science (New York, NY)"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"R1269","DOI":"10.1152\/ajpregu.00442.2002","article-title":"Short-chain fatty acids stimulate colonic transit via intraluminal 5-HT release in rats","volume":"284","author":"Fukumoto","year":"2003","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.cell.2015.02.047","article-title":"Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis","volume":"161","author":"Yano","year":"2015","journal-title":"Cell"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"e1900867","DOI":"10.1002\/mnfr.201900867","article-title":"Late-night eating-induced physiological dysregulation and circadian misalignment are accompanied by microbial Dysbiosis","volume":"63","author":"Ni","year":"2019","journal-title":"Mol Nutr Food Res"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"489","DOI":"10.3390\/cells9020489","article-title":"Melatonin orchestrates lipid homeostasis through the Hepatointestinal circadian clock and microbiota during constant light exposure","volume":"9","author":"Hong","year":"2020","journal-title":"Cells"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1080\/07420528.2020.1778717","article-title":"The circadian disruption of night work alters gut microbiota consistent with elevated risk for future metabolic and gastrointestinal pathology","volume":"37","author":"Morta\u015f","year":"2020","journal-title":"Chronobiol Int"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"2569","DOI":"10.3390\/nu14132569","article-title":"The effects of time-restricted eating on metabolism and gut microbiota: a real-life study","volume":"14","author":"Ferrocino","year":"2022","journal-title":"Nutrients"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"105702","DOI":"10.1016\/j.ecolind.2019.105702","article-title":"The effects of artificial light at night on Eurasian tree sparrow (Passer montanus): behavioral rhythm disruption, melatonin suppression and intestinal microbiota alterations","volume":"108","author":"Jiang","year":"2020","journal-title":"Ecol Indic"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1152\/japplphysiol.01413.2009","article-title":"Blue light from light-emitting diodes elicits a dose-dependent suppression of melatonin in humans","volume":"110","author":"West","year":"2011","journal-title":"J Appl Physiol"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1900","DOI":"10.1007\/s10753-024-02162-8","article-title":"Brief disruption of circadian rhythms alters intestinal barrier integrity and modulates DSS-induced colitis severity in mice","volume":"48","author":"Barrios","year":"2025","journal-title":"Inflammation"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/0165-1781(89)90047-4","article-title":"The Pittsburgh sleep quality index: a new instrument for psychiatric practice and research","volume":"28","author":"Buysse","year":"1989","journal-title":"Psychiatry Res"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1301818","DOI":"10.3389\/fnut.2023.1301818","article-title":"Sleep, activity, and diet in harmony: unveiling the relationships of chronotype, sleep quality, physical activity, and dietary intake","volume":"10","author":"G\u00fcnal","year":"2023","journal-title":"Front Nutr"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"100730","DOI":"10.1016\/j.bbih.2024.100730","article-title":"Stress and depression-associated shifts in gut microbiota: a pilot study of human pregnancy","volume":"36","author":"Rajasekera","year":"2024","journal-title":"Brain Behav Immun Health"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1017\/S0007114519003428","article-title":"Effect of time-restricted feeding on metabolic risk and circadian rhythm associated with gut microbiome in healthy males","volume":"123","author":"Zeb","year":"2020","journal-title":"Br J Nutr"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1162482","DOI":"10.3389\/fmicb.2023.1162482","article-title":"Time-restricted feeding affects colonic nutrient substrates and modulates the diurnal fluctuation of microbiota in pigs","volume":"14","author":"Wang","year":"2023","journal-title":"Front Microbiol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.1073\/pnas.1418490112","article-title":"Evening use of light-emitting eReaders negatively affects sleep, circadian timing, and next-morning alertness","volume":"112","author":"Chang","year":"2015","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.jpsychires.2017.10.015","article-title":"Blocking nocturnal blue light for insomnia: a randomized controlled trial","volume":"96","author":"Shechter","year":"2018","journal-title":"J Psychiatr Res"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1186\/s12888-025-07181-9","article-title":"Association among objective and subjective sleep duration, depressive symptoms and all-cause mortality: the pathways study","volume":"25","author":"Zeng","year":"2025","journal-title":"BMC Psychiatry"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"27677","DOI":"10.1038\/s41598-025-10783-8","article-title":"An integrative analysis of cell-specific transcriptomics and nuclear proteomics of sleep-deprived mouse cerebral cortex","volume":"15","author":"Jha","year":"2025","journal-title":"Sci Rep"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"e2502053","DOI":"10.4014\/jmb.2502.02053","article-title":"Longitudinal analysis of the Immunostimulatory properties and safety profile of Lacticaseibacillus rhamnosus LRa05 as a dietary supplement","volume":"35","author":"Wu","year":"2025","journal-title":"J Microbiol Biotechnol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"e22011","DOI":"10.1096\/fj.202100857RR","article-title":"Metagenomic analysis reveals the signature of gut microbiota associated with human chronotypes","volume":"35","author":"Carasso","year":"2021","journal-title":"FASEB J"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1152\/physiolgenomics.00095.2018","article-title":"Aging, melatonin biosynthesis, and circadian clockworks in the gastrointestinal system of the laboratory mouse","volume":"51","author":"Paulose","year":"2019","journal-title":"Physiol Genomics"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"2221450","DOI":"10.1080\/19490976.2023.2221450","article-title":"Resynchronized rhythmic oscillations of gut microbiota drive time-restricted feeding induced nonalcoholic steatohepatitis alleviation","volume":"15","author":"Xia","year":"2023","journal-title":"Gut Microbes"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1038\/s41467-022-28662-5","article-title":"Randomized controlled trial for time-restricted eating in healthy volunteers without obesity","volume":"13","author":"Xie","year":"2022","journal-title":"Nat Commun"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1038\/s41398-023-02614-z","article-title":"Melatonin alleviates depression-like behaviors and cognitive dysfunction in mice by regulating the circadian rhythm of AQP4 polarization","volume":"13","author":"Yao","year":"2023","journal-title":"Transl Psychiatry"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"e1013139","DOI":"10.1371\/journal.ppat.1013139","article-title":"Regulation of diel locomotor activity and retinal responses of Anopheles stephensi by ingested histamine and serotonin is temperature- and infection-dependent","volume":"21","author":"Ochwedo","year":"2025","journal-title":"PLoS Pathog"}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2025.1678482\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T05:35:22Z","timestamp":1759383322000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2025.1678482\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,2]]},"references-count":35,"alternative-id":["10.3389\/fnut.2025.1678482"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2025.1678482","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,2]]},"article-number":"1678482"}}