{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T06:04:45Z","timestamp":1780639485216,"version":"3.54.1"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"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. Microbiol."],"abstract":"\n Introduction<\/jats:title>\n Sleep deprivation (SD) is increasingly recognized as a risk factor for metabolic and hepatic disorders, yet the temporal dynamics linking gut dysbiosis to liver injury remain poorly characterized.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n In this study, we established a platform-based SD model in a total of 24 C57BL\/6J mice (\n n<\/jats:italic>\n = 4 per group per weekly time point) over 3 weeks and systematically investigated the weekly progression of gut microbiome alterations, hepatic metabolite profiles, and liver injury markers using Accu16S\n \u00ae<\/jats:sup>\n absolute quantification sequencing and untargeted LC-MS\/MS metabolomics.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Our results revealed a temporally ordered three-stage cascade of gut-liver axis disruption. In week 1, core probiotics including\n Bifidobacterium<\/jats:italic>\n and\n Dubosiella<\/jats:italic>\n declined concurrently with protective metabolites such as tryptamine and glycocholic acid, alongside perturbation of primary bile acid biosynthesis. In week 2, concurrent enrichment of a compensatory Lactobacillaceae member (\n Ligilactobacillus<\/jats:italic>\n ) and an opportunistic pathogen (\n Streptococcus<\/jats:italic>\n ) was accompanied by reduced microbiota\u2013metabolite correlation density, coinciding with peak serum ALT\/AST levels and metabolic pathway remodeling involving nucleotide sugar and tryptophan metabolism. By week 3, synchronous decline of\n Lactobacillus<\/jats:italic>\n ,\n Bifidobacterium<\/jats:italic>\n , and\n Dubosiella<\/jats:italic>\n coincided with full-scale activation of arachidonic acid metabolism and inflammatory immune pathways, accompanied by elevated serum LPS levels suggestive of intestinal barrier perturbation. Correlation analyses revealed that the progressive depletion of beneficial bacteria was associated with the sequential loss of protective metabolites, reorganization of the metabolic network, and inflammatory mediator accumulation, although these relationships remain correlational and require causal validation.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n These findings describe a \u201cprotective loss\u2013homeostatic decoupling\u2013inflammatory signature\u201d descriptive model. Because these findings are based on correlation analyses in a mouse model without causal validation, further mechanistic and interventional studies are required before any clinical implications can be drawn.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1846136","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:40:21Z","timestamp":1780638021000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["From probiotic depletion to inflammatory cascade: multi-omics reveals the temporal progression of sleep deprivation-induced gut-liver axis disruption in mice"],"prefix":"10.3389","volume":"17","author":[{"given":"Ming-Kun","family":"Dai","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital of Kunming Medical University, Kunming","place":["Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Kuang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital of Kunming Medical University, Kunming","place":["Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Fei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Burns Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming","place":["Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Xiao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital of Kunming Medical University, Kunming","place":["Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Fan","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital of Kunming Medical University, Kunming","place":["Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital of Kunming Medical University, Kunming","place":["Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Lin","family":"Tai","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital of Kunming Medical University, Kunming","place":["Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"24828","DOI":"10.1038\/srep24828","article-title":"Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses.","volume":"6","author":"Aho","year":"2016","journal-title":"Sci. Rep."},{"key":"B2","doi-asserted-by":"publisher","first-page":"682290","DOI":"10.3389\/fmicb.2021.682290","article-title":"Antidiabetic function of Lactobacillus fermentum MF423-fermented rice bran and its effect on gut microbiota structure in type 2 diabetic mice.","volume":"12","author":"Ai","year":"2021","journal-title":"Front. Microbiol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1016\/j.jhep.2019.10.003","article-title":"The gut-liver axis in liver disease: pathophysiological basis for therapy.","volume":"72","author":"Albillos","year":"2020","journal-title":"J. Hepatol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1016\/j.molmet.2016.10.003","article-title":"Gut microbiota and glucometabolic alterations in response to recurrent partial sleep deprivation in normal-weight young individuals.","volume":"5","author":"Benedict","year":"2016","journal-title":"Mol. Metab."},{"key":"B5","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1007\/978-94-024-0945-1_4","article-title":"Vitamin A absorption, storage and mobilization.","volume":"81","author":"Blaner","year":"2016","journal-title":"Subcell Biochem."},{"key":"B6","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1038\/s41587-019-0209-9","article-title":"Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2.","volume":"37","author":"Bolyen","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1038\/nature13828","article-title":"Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile.","volume":"517","author":"Buffie","year":"2015","journal-title":"Nature"},{"key":"B8","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1038\/nmeth.3869","article-title":"DADA2: high-resolution sample inference from Illumina amplicon data.","volume":"13","author":"Callahan","year":"2016","journal-title":"Nat. Methods"},{"key":"B9","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/nrendo.2015.128","article-title":"Short-chain fatty acids in control of body weight and insulin sensitivity.","volume":"11","author":"Canfora","year":"2015","journal-title":"Nat. Rev. Endocrinol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1038\/s41574-019-0156-z","article-title":"Gut microbial metabolites in obesity, NAFLD and T2DM.","volume":"15","author":"Canfora","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/healthcare7010001","article-title":"The global problem of insufficient sleep and its serious public health implications.","volume":"7","author":"Chattu","year":"2018","journal-title":"Healthcare"},{"key":"B12","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.niox.2011.04.004","article-title":"Synthesis and recycling of tetrahydrobiopterin in endothelial function and vascular disease.","volume":"25","author":"Crabtree","year":"2011","journal-title":"Nitric Oxide"},{"key":"B13","doi-asserted-by":"publisher","first-page":"37","DOI":"10.3390\/clockssleep4010006","article-title":"Depriving mice of sleep also deprives of food.","volume":"4","author":"\u0110ukanovi\u0107","year":"2022","journal-title":"Clocks Sleep"},{"key":"B14","doi-asserted-by":"publisher","first-page":"9066","DOI":"10.1073\/pnas.1219451110","article-title":"Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity.","volume":"110","author":"Everard","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B15","doi-asserted-by":"publisher","first-page":"R905","DOI":"10.1152\/ajpregu.2000.278.4.R905","article-title":"Systemic bacterial invasion induced by sleep deprivation.","volume":"278","author":"Everson","year":"2000","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1038\/nature07204","article-title":"The development of allergic inflammation.","volume":"454","author":"Galli","year":"2008","journal-title":"Nature"},{"key":"B17","doi-asserted-by":"publisher","first-page":"e74963","DOI":"10.1371\/journal.pone.0074963","article-title":"Commensal Akkermansia muciniphila exacerbates gut inflammation in Salmonella typhimurium-infected gnotobiotic mice.","volume":"8","author":"Ganesh","year":"2013","journal-title":"PLoS One"},{"key":"B18","doi-asserted-by":"publisher","first-page":"200","DOI":"10.4056\/sigs.1714269","article-title":"Complete genome sequence of Odoribacter splanchnicus type strain (1651\/6).","volume":"4","author":"G\u00f6ker","year":"2011","journal-title":"Stand. Genomic Sci."},{"key":"B19","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1016\/j.cell.2009.09.033","article-title":"Induction of intestinal Th17 cells by segmented filamentous bacteria.","volume":"139","author":"Ivanov","year":"2009","journal-title":"Cell."},{"key":"B20","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1054\/plef.2002.0454","article-title":"Suppression of cyclooxygenase-2 and inducible nitric oxide synthase expression by conjugated linoleic acid in murine macrophages.","volume":"67","author":"Iwakiri","year":"2002","journal-title":"Prostaglandins Leukot Essent Fatty Acids"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1002\/hep.22109","article-title":"Public policy committee of the american association for the study of liver disease. serum activity of alanine aminotransferase (ALT) as an indicator of health and disease.","volume":"47","author":"Kim","year":"2008","journal-title":"Hepatology"},{"key":"B22","doi-asserted-by":"publisher","first-page":"17808","DOI":"10.1073\/pnas.1312937110","article-title":"Polyunsaturated fatty acid saturation by gut lactic acid bacteria affecting host lipid composition.","volume":"110","author":"Kishino","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B23","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1038\/nm.4102","article-title":"CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands.","volume":"22","author":"Lamas","year":"2016","journal-title":"Nat. Med."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1038\/s41564-021-00970-4","article-title":"Bifidobacterium species associated with breastfeeding produce aromatic lactic acids in the infant gut.","volume":"6","author":"Laursen","year":"2021","journal-title":"Nat Microbiol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.brainres.2004.01.019","article-title":"Sleep deprivation induced by the modified multiple platform technique: quantification of sleep loss and recovery.","volume":"1004","author":"Machado","year":"2004","journal-title":"Brain Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"832151","DOI":"10.3389\/fmicb.2022.832151","article-title":"The protective effects of inulin-type fructans against high-fat\/sucrose diet-induced gestational diabetes mice in association with gut microbiota regulation.","volume":"13","author":"Miao","year":"2022","journal-title":"Front. Microbiol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"35405","DOI":"10.1038\/srep35405","article-title":"Chronic sleep disruption alters gut microbiota, induces systemic and adipose tissue inflammation and insulin resistance in mice.","volume":"6","author":"Poroyko","year":"2016","journal-title":"Sci. Rep."},{"key":"B28","doi-asserted-by":"publisher","first-page":"12696","DOI":"10.1021\/acs.jafc.8b04874","article-title":"Antidiabetic effects of Lactobacillus casei fermented yogurt through reshaping gut microbiota structure in type 2 diabetic rats.","volume":"66","author":"Qu","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"B29","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1161\/ATVBAHA.110.207449","article-title":"Prostaglandins and inflammation.","volume":"31","author":"Ricciotti","year":"2011","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1097\/MOG.0000000000000057","article-title":"Bile acids and the gut microbiome.","volume":"30","author":"Ridlon","year":"2014","journal-title":"Curr. Opin. Gastroenterol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"3294","DOI":"10.1038\/s41467-018-05470-4","article-title":"Microbial tryptophan catabolites in health and disease.","volume":"9","author":"Roager","year":"2018","journal-title":"Nat. Commun."},{"key":"B32","doi-asserted-by":"publisher","first-page":"225","DOI":"10.4062\/biomolther.2017.251","article-title":"Effects and mechanisms of taurine as a therapeutic agent.","volume":"26","author":"Schaffer","year":"2018","journal-title":"Biomol. Ther."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1038\/nm.4185","article-title":"Signals from the gut microbiota to distant organs in physiology and disease.","volume":"22","author":"Schroeder","year":"2016","journal-title":"Nat. Med."},{"key":"B34","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1159\/000312669","article-title":"Cysteinyl leukotrienes and their receptors: molecular and functional characteristics.","volume":"85","author":"Singh","year":"2010","journal-title":"Pharmacology"},{"key":"B35","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1126\/science.1241165","article-title":"The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis.","volume":"341","author":"Smith","year":"2013","journal-title":"Science"},{"key":"B36","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/s0006-8993(00)02531-2","article-title":"Sleep rebound in animals deprived of paradoxical sleep by the modified multiple platform method.","volume":"875","author":"Suchecki","year":"2000","journal-title":"Brain Res."},{"key":"B37","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1038\/s41575-018-0011-z","article-title":"The gut-liver axis and the intersection with the microbiome.","volume":"15","author":"Tripathi","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.cmet.2016.05.005","article-title":"Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism.","volume":"24","author":"Wahlstr\u00f6m","year":"2016","journal-title":"Cell Metab."},{"key":"B39","doi-asserted-by":"publisher","first-page":"3738","DOI":"10.1016\/j.scib.2025.04.042","article-title":"Bifidobacterium animalis subsp. Lactis A6 alleviates comorbid constipation and depression by rebalancing tryptophan metabolism.","volume":"70","author":"Wang","year":"2025","journal-title":"Sci. Bull."},{"key":"B40","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1016\/j.chom.2014.09.001","article-title":"Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine.","volume":"16","author":"Williams","year":"2014","journal-title":"Cell Host Microbe"},{"key":"B41","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 Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1846136\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:40:22Z","timestamp":1780638022000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1846136\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,5]]},"references-count":41,"alternative-id":["10.3389\/fmicb.2026.1846136"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2026.1846136","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,5]]},"article-number":"1846136"}}