{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T04:56:01Z","timestamp":1774673761980,"version":"3.50.1"},"reference-count":87,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,4,18]],"date-time":"2022-04-18T00:00:00Z","timestamp":1650240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01 DK130227"],"award-info":[{"award-number":["R01 DK130227"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01 DK120679"],"award-info":[{"award-number":["R01 DK120679"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["P50 AA024333"],"award-info":[{"award-number":["P50 AA024333"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["U01 AA026938"],"award-info":[{"award-number":["U01 AA026938"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart Lung and Blood Institute","doi-asserted-by":"publisher","award":["P01 HL147823"],"award-info":[{"award-number":["P01 HL147823"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart Lung and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL144651"],"award-info":[{"award-number":["R01 HL144651"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart Lung and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL130819"],"award-info":[{"award-number":["R01 HL130819"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Exposure to some environmental pollutants can have potent endocrine-disrupting effects, thereby promoting hormone imbalance and cardiometabolic diseases such as non-alcoholic fatty liver disease (NAFLD), diabetes, and cardiorenal diseases. Recent evidence also suggests that many environmental pollutants can reorganize the gut microbiome to potentially impact these diverse human diseases. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is among the most potent endocrine-disrupting dioxin pollutants, yet our understanding of how TCDD impacts the gut microbiome and systemic metabolism is incompletely understood. Here, we show that TCDD exposure in mice profoundly stimulates the hepatic expression of flavin-containing monooxygenase 3 (Fmo3), which is a hepatic xenobiotic metabolizing enzyme that is also responsible for the production of the gut microbiome-associated metabolite trimethylamine N-oxide (TMAO). Interestingly, an enzymatic product of FMO3 (TMAO) has been associated with the same cardiometabolic diseases that these environmental pollutants promote. Therefore, here, we examined TCDD-induced alterations in the gut microbiome, host liver transcriptome, and glucose tolerance in Fmo3+\/+ and Fmo3\u2212\/\u2212 mice. Our results show that Fmo3 is a critical component of the transcriptional response to TCDD, impacting the gut microbiome, host liver transcriptome, and systemic glucose tolerance. Collectively, this work uncovers a previously underappreciated role for Fmo3 in integrating diet\u2013pollutant\u2013microbe\u2013host interactions.<\/jats:p>","DOI":"10.3390\/metabo12040364","type":"journal-article","created":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T01:03:01Z","timestamp":1650330181000},"page":"364","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Flavin-Containing Monooxygenase 3 (FMO3) Is Critical for Dioxin-Induced Reorganization of the Gut Microbiome and Host Insulin Sensitivity"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2087-6048","authenticated-orcid":false,"given":"William","family":"Massey","sequence":"first","affiliation":[{"name":"Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic, Lerner Research Institute, Cleveland, OH 44195, USA"},{"name":"Center for Microbiome & Human Health, Cleveland Clinic, Lerner Research Institute, Cleveland, OH 44195, USA"},{"name":"Department of Molecular Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0077-9192","authenticated-orcid":false,"given":"Lucas J.","family":"Osborn","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic, Lerner Research Institute, Cleveland, OH 44195, USA"},{"name":"Center for Microbiome & Human Health, Cleveland Clinic, Lerner Research Institute, Cleveland, OH 44195, USA"},{"name":"Department of Molecular Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rakhee","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic, Lerner Research Institute, Cleveland, OH 44195, USA"},{"name":"Center for Microbiome & Human Health, Cleveland Clinic, Lerner Research Institute, Cleveland, OH 44195, USA"},{"name":"Department of Molecular Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony","family":"Horak","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic, Lerner Research Institute, Cleveland, OH 44195, USA"},{"name":"Center for Microbiome & Human Health, Cleveland Clinic, Lerner Research Institute, Cleveland, OH 44195, USA"},{"name":"Department of Molecular Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4755-1371","authenticated-orcid":false,"given":"Kevin K.","family":"Fung","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic, Lerner Research Institute, Cleveland, OH 44195, USA"},{"name":"Center for Microbiome & Human Health, Cleveland Clinic, Lerner Research Institute, Cleveland, OH 44195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danny","family":"Orabi","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic, Lerner Research Institute, Cleveland, OH 44195, USA"},{"name":"Center for Microbiome & Human Health, Cleveland Clinic, Lerner Research Institute, Cleveland, OH 44195, USA"},{"name":"Department of Molecular Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"},{"name":"Department of General Surgery, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. Ricky","family":"Chan","sequence":"additional","affiliation":[{"name":"Institute for Computational Biology, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naseer","family":"Sangwan","sequence":"additional","affiliation":[{"name":"Center for Microbiome & Human Health, Cleveland Clinic, Lerner Research Institute, Cleveland, OH 44195, USA"},{"name":"Microbial Sequencing & Analytics Core Facility, Cleveland Clinic, Lerner Research Institute, Cleveland, OH 44195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6455-8228","authenticated-orcid":false,"given":"Zeneng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic, Lerner Research Institute, Cleveland, OH 44195, USA"},{"name":"Center for Microbiome & Human Health, Cleveland Clinic, Lerner Research Institute, Cleveland, OH 44195, USA"},{"name":"Department of Molecular Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. Mark","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic, Lerner Research Institute, Cleveland, OH 44195, USA"},{"name":"Center for Microbiome & Human Health, Cleveland Clinic, Lerner Research Institute, Cleveland, OH 44195, USA"},{"name":"Department of Molecular Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kim, Y.A., Park, J.B., Woo, M.S., Lee, S.Y., Kim, H.Y., and Yoo, Y.H. (2019). Persistent Organic Pollutant-Mediated Insulin Resistance. Int. J. Environ. Res. 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