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However, limited research has been reported on these metabolic profile changes, particularly using models of alcohol dependence such as after chronic intermittent ethanol (CIE) vapor exposure. This study investigated CIE-induced metabolomic alterations of CIE were investigated using fecal, liver, and serum samples of adult male and female C57BL\/6J mice following 72 hr withdrawal. Significant metabolite changes were observed in both fecal and liver extracts and these changes were sex-specific. Both liver and fecal metabolites had systematic changes, while blood serum influences were limited after CIE. Female fecal samples showed higher metabolite perturbations than male samples according to PCA studies. The female samples showed significant butyrate downregulation and acetate upregulation, which are critical microbial products as beneficial microbe cell energy sources and influence intestinal absorption in the host. In addition, the female fecal samples showed significant downregulation of branched-chain amino acids including leucine, isoleucine, and valine, while male samples showed downregulation of glucose and taurine, with upregulated phenylalanine and tyrosine. In contrast, in the liver study, phenylalanine and tyrosine were upregulated while taurine was downregulated in females. Both sexes showed downregulation of liver glycine and glucose. These data indicate that CIE induces sex-specific metabolic perturbations in the mouse liver and fecal metabolome, and have implications for guy disturbances and liver damage observed following alcohol dependence. This study provides potential targets for future examination of mechanisms and treatment approaches for alcohol dependence.<\/jats:p>","DOI":"10.64898\/2026.06.14.732186","type":"posted-content","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T21:40:12Z","timestamp":1781818812000},"source":"Crossref","is-referenced-by-count":0,"title":["Chronic Intermittent Ethanol Exposure Produces Sex- and Tissue-Specific Metabolomic Signatures Across the Gut-Liver Axis in Adult Mice"],"prefix":"10.64898","author":[{"given":"Julie","family":"Pollak","sequence":"first","affiliation":[{"name":"Department of Chemistry and Chemical Engineering, Florida Institute of Technology, Melbourne, FL 32901-6975"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3440-6482","authenticated-orcid":false,"given":"Reginald","family":"Cannady","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science and Technology, North Carolina Agricultural and Technical State University, Greensboro, North Carolina 27411, U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Engineering, Florida Institute of Technology, Melbourne, FL 32901-6975"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2701-0095","authenticated-orcid":false,"given":"Antoniette M.","family":"Maldonado-Devincci","sequence":"additional","affiliation":[{"name":"Department of Psychology, Hairston College of Health and Human Sciences, North Carolina Agricultural and Technical State University, Greensboro, North Carolina 27411, U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026062105501170000_2026.06.14.732186v1.1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241411236"},{"key":"2026062105501170000_2026.06.14.732186v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.10.003"},{"key":"2026062105501170000_2026.06.14.732186v1.3","unstructured":"Alcohol-Related Emergencies and Deaths in the United States (2026a)."},{"key":"2026062105501170000_2026.06.14.732186v1.4","unstructured":"Alcohol-Related Emergencies and Deaths in the United States (2026b)."},{"key":"2026062105501170000_2026.06.14.732186v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-018-0099-1"},{"key":"2026062105501170000_2026.06.14.732186v1.6","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2001.tb02242.x"},{"key":"2026062105501170000_2026.06.14.732186v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/b978-0-12-405941-2.00019-5"},{"key":"2026062105501170000_2026.06.14.732186v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2017.04.028"},{"key":"2026062105501170000_2026.06.14.732186v1.9","doi-asserted-by":"publisher","DOI":"10.1097\/01.ALC.0000149977.95306.3A"},{"key":"2026062105501170000_2026.06.14.732186v1.10","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23963"},{"key":"2026062105501170000_2026.06.14.732186v1.11","doi-asserted-by":"publisher","DOI":"10.1002\/ueg2.12370"},{"key":"2026062105501170000_2026.06.14.732186v1.12","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1016\/j.jpain.2023.02.024","article-title":"Mechanical and heat hyperalgesia upon withdrawal from chronic intermittent ethanol vapor depends on sex, exposure duration, and blood alcohol concentration in mice","volume":"24","year":"2023","journal-title":"The Journal of Pain"},{"key":"2026062105501170000_2026.06.14.732186v1.13","unstructured":"CDC (2025). 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