{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:59:56Z","timestamp":1789624796856,"version":"build-2803163510"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Evidence suggests that circadian rhythm disorder is associated with a variety of gastrointestinal diseases, and the circadian rhythm plays a key role in maintaining the homeostasis of intestinal flora. The underlying mechanisms are still not completely identified. This study was aimed to explore whether jet lag-caused circadian disruption influences gut microbiome and its metabolites.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mice were synchronized with 12-h light\/dark cycles (control group) or subjected to daily 8-h advance of the light\/dark cycle for every 3 days (jet-lagged group). Four months later, fecal samples and jejunal contents were collected and analyzed by 16S rRNA gene sequencing. In addition, fecal samples were subjected to metabolome analysis with ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS\/MS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results of 16s rRNA sequencing showed that chronic jet lag led to decreased microbial abundance, richness, and diversity in both feces and jejunal contents. ANOSIM analysis revealed significant difference between control and jet-lagged groups. As the colonic microbiome, the abundance of Bacteroidetes phylum was significantly decreased and that of Actinobacteria phylum was increased in jet-lagged mice. Jet lag increased the ratio of Firmicutes to Bacteroidetes, an indicator for the imbalance of gut microbiota. Metabolome analysis of fecal samples showed that the levels of tryptophan and its derivatives were decreased in jet-lagged mice. In addition, fecal\u00a0levels of secondary bile acids changed under jet lag conditions. Correlation analysis identified associations between tryptophan (and its derivatives) levels and colonic\u00a0microbiota.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study presents a comprehensive landscape of gut microbiota and its metabolites in mice subjected to chronic jet lag. The results suggest that circadian disruption may lead to changes in fecal and jejunal microbiota and fecal metabolites. Moreover, our results demonstrate a novel interplay between the gut microbiome and\u00a0metabolome.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2021.648175","type":"journal-article","created":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T06:15:30Z","timestamp":1622528130000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["Chronic Jet Lag Exacerbates Jejunal and Colonic Microenvironment in Mice"],"prefix":"10.3389","volume":"11","author":[{"given":"Qing","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Yi","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu-Juan","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian-Qian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Liang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1016\/j.chom.2018.05.003","article-title":"Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease","volume":"23","author":"Agus","year":"2018","journal-title":"Cell Host Microbe"},{"key":"B2","doi-asserted-by":"publisher","first-page":"bqaa059","DOI":"10.1210\/endocr\/bqaa059","article-title":"The Microbiome as a Circadian Coordinator of Metabolism","volume":"161","author":"Alvarez","year":"2020","journal-title":"Endocrinology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"645","DOI":"10.3109\/00365521003702734","article-title":"Bile Acids: Short and Long Term Effects in the Intestine","volume":"45","author":"Bajor","year":"2010","journal-title":"Scand. J. Gastroenterol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/j.dld.2018.02.012","article-title":"Actinobacteria: A Relevant Minority for the Maintenance of Gut Homeostasis","volume":"50","author":"Binda","year":"2018","journal-title":"Dig. Liver Dis."},{"key":"B5","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1002\/ajim.20099","article-title":"Relationship of Work Schedules to Gastrointestinal Diagnoses, Symptoms, and Medication Use in Auto Factory Workers","volume":"46","author":"Caruso","year":"2004","journal-title":"Am. J. Ind. Med."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202000681","article-title":"Egf Relays Signals to COP1 and Facilitates Foxo4 Degradation to Promote Tumorigenesis","volume":"7","author":"Choi","year":"2020","journal-title":"Adv. Sci. (Weinh)"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1038\/s41430-020-0607-6","article-title":"Profile of the Gut Microbiota of Adults With Obesity: A Systematic Review","volume":"74","author":"Crovesy","year":"2020","journal-title":"Eur. J. Clin. Nutr."},{"key":"B8","doi-asserted-by":"publisher","first-page":"946","DOI":"10.3390\/nu12040946","article-title":"The Relationship Between the Infant Gut Microbiota and Allergy. The Role of Bifidobacterium Breve and Prebiotic Oligosaccharides in the Activation of Anti-Allergic Mechanisms in Early Life","volume":"12","author":"Cukrowska","year":"2020","journal-title":"Nutrients"},{"key":"B9","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1111\/cei.13158","article-title":"The Microbiome in Autoimmune Diseases","volume":"195","author":"De Luca","year":"2019","journal-title":"Clin. Exp. Immunol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"R37","DOI":"10.1530\/JOE-13-0131","article-title":"The Gut Microbiome: The Role of a Virtual Organ in the Endocrinology of the Host","volume":"218","author":"Evans","year":"2013","journal-title":"J. Endocrinol."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12574","article-title":"Role of Melatonin in Sleep Deprivation-Induced Intestinal Barrier Dysfunction in Mice","volume":"67","author":"Gao","year":"2019","journal-title":"J. Pineal. Res."},{"key":"B12","doi-asserted-by":"publisher","first-page":"13","DOI":"10.3390\/jpm11010013","article-title":"Gallstone Disease, Obesity and the Firmicutes\/Bacteroidetes Ratio as a Possible Biomarker of Gut Dysbiosis","volume":"11","author":"Grigor\u2019eva","year":"2020","journal-title":"J. Pers. Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/s41586-019-1785-z","article-title":"Bile Acid Metabolites Control TH17 and Treg Cell Differentiation","volume":"576","author":"Hang","year":"2019","journal-title":"Nature"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.BAD-0010-2016","article-title":"Bifidobacteria and Their Health-Promoting Effects","volume":"5","author":"Hidalgo-Cantabrana","year":"2017","journal-title":"Microbiol. Spectr."},{"key":"B15","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1038\/nri2710","article-title":"Immune Adaptations That Maintain Homeostasis With the Intestinal Microbiota","volume":"10","author":"Hooper","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1657","DOI":"10.1038\/s41418-018-0070-2","article-title":"Lactobacillus Accelerates ISCs Regeneration to Protect the Integrity of Intestinal Mucosa Through Activation of STAT3 Signaling Pathway Induced by LPLs Secretion of IL-22","volume":"25","author":"Hou","year":"2018","journal-title":"Cell Death Differ."},{"key":"B17","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.jnutbio.2016.12.019","article-title":"Dietary Tryptophan Alleviates Dextran Sodium Sulfate-Induced Colitis Through Aryl Hydrocarbon Receptor in Mice","volume":"42","author":"Islam","year":"2017","journal-title":"J. Nutr. Biochem."},{"key":"B18","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1038\/nrgastro.2017.119","article-title":"Bile Acid-Microbiota Crosstalk in Gastrointestinal Inflammation and Carcinogenesis","volume":"15","author":"Jia","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.cmet.2016.06.004","article-title":"Itaconate Links Inhibition of Succinate Dehydrogenase With Macrophage Metabolic Remodeling and Regulation of Inflammation","volume":"24","author":"Lampropoulou","year":"2016","journal-title":"Cell Metab."},{"key":"B20","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.cmet.2019.11.001","article-title":"Gut Microbiome Fermentation Determines the Efficacy of Exercise for Diabetes Prevention","volume":"31","author":"Liu","year":"2020","journal-title":"Cell Metab."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1474","DOI":"10.3390\/nu12051474","article-title":"The Firmicutes\/Bacteroidetes Ratio: A Relevant Marker of Gut Dysbiosis in Obese Patients","volume":"12","author":"Magne","year":"2020","journal-title":"Nutrients"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2020.101340","article-title":"Sleep, Circadian Rhythm, and Gut Microbiota","volume":"53","author":"Matenchuk","year":"2020","journal-title":"Sleep Med. Rev."},{"key":"B23","doi-asserted-by":"publisher","first-page":"6670","DOI":"10.1038\/s41598-018-25190-5","article-title":"Ketogenic Diet Enhances Neurovascular Function With Altered Gut Microbiome in Young Healthy Mice","volume":"8","author":"Ma","year":"2018","journal-title":"Sci. Rep."},{"key":"B24","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1172\/JCI76304","article-title":"Gut\/Brain Axis and the Microbiota","volume":"125","author":"Mayer","year":"2015","journal-title":"J. Clin. Invest."},{"key":"B25","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1016\/j.cmet.2020.09.004","article-title":"The Gut Microbiota At the Service of Immunometabolism","volume":"32","author":"Michaudel","year":"2020","journal-title":"Cell Metab."},{"key":"B26","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1210\/er.2016-1083","article-title":"Circadian Rhythm and Sleep Disruption: Causes, Metabolic Consequences, and Countermeasures","volume":"37","author":"Potter","year":"2016","journal-title":"Endocr. Rev."},{"key":"B27","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1186\/s13073-019-0704-0","article-title":"Genomics of Circadian Rhythms in Health and Disease","volume":"11","author":"Rijo-Ferreira","year":"2019","journal-title":"Genome Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1038\/nri.2016.42","article-title":"Gut Microbiota, Metabolites and Host Immunity","volume":"16","author":"Rooks","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.cmet.2013.01.003","article-title":"Gut Microbiota Regulates Bile Acid Metabolism by Reducing the Levels of Tauro-Beta-Muricholic Acid, a Naturally Occurring FXR Antagonist","volume":"17","author":"Sayin","year":"2013","journal-title":"Cell Metab."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1715","DOI":"10.3390\/microorganisms8111715","article-title":"The Influence of Probiotics on the Firmicutes\/Bacteroidetes Ratio in the Treatment of Obesity and Inflammatory Bowel Disease","volume":"8","author":"Stojanov","year":"2020","journal-title":"Microorganisms"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0067102","article-title":"Disruption of the Circadian Clock in Mice Increases Intestinal Permeability and Promotes Alcohol-Induced Hepatic Pathology and Inflammation","volume":"8","author":"Summa","year":"2013","journal-title":"PloS One"},{"key":"B32","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1186\/s12866-017-1059-6","article-title":"The Human Jejunum has an Endogenous Microbiota That Differs From Those in the Oral Cavity and Colon","volume":"17","author":"Sundin","year":"2017","journal-title":"BMC Microbiol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/B978-0-12-800100-4.00003-9","article-title":"The Role of Short-Chain Fatty Acids in Health and Disease","volume":"121","author":"Tan","year":"2014","journal-title":"Adv. Immunol."},{"key":"B34","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":"B35","doi-asserted-by":"publisher","first-page":"1441","DOI":"10.1016\/j.cell.2020.08.027","article-title":"Diet Diurnally Regulates Small Intestinal Microbiome-Epithelial-Immune Homeostasis and Enteritis","volume":"182","author":"Tuganbaev","year":"2020","journal-title":"Cell"},{"key":"B36","doi-asserted-by":"publisher","first-page":"5709","DOI":"10.1021\/acs.analchem.0c04686","article-title":"A Metabolite Array Technology for Precision Medicine","volume":"93","author":"Xie","year":"2021","journal-title":"Anal. Chem."},{"key":"B37","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1016\/j.immuni.2013.08.003","article-title":"Tryptophan Catabolites From Microbiota Engage Aryl Hydrocarbon Receptor and Balance Mucosal Reactivity Via Interleukin-22","volume":"39","author":"Zelante","year":"2013","journal-title":"Immunity"}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2021.648175\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T06:15:32Z","timestamp":1622528132000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2021.648175\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,1]]},"references-count":37,"alternative-id":["10.3389\/fcimb.2021.648175"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2021.648175","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,1]]},"article-number":"648175"}}