Estrogen-mediated gut microbiome alterations influence sexual dimorphism in metabolic syndrome in mice

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dc.contributor.authorKaliannan, Kanakaraju
dc.contributor.authorRobertson, Ruairi C.
dc.contributor.authorMurphy, Kiera
dc.contributor.authorStanton, Catherine
dc.contributor.authorKang, Chao
dc.contributor.authorWang, Bin
dc.contributor.authorHao, Lei
dc.contributor.authorBhan, Atul K.
dc.contributor.authorKang, Jing X.
dc.contributor.funderSansun Life Sciencesen
dc.contributor.funderFortune Education Foundationen
dc.date.accessioned2019-07-18T12:09:11Z
dc.date.available2019-07-18T12:09:11Z
dc.date.issued2018-11-13
dc.description.abstractBackground: Understanding the mechanism of the sexual dimorphism in susceptibility to obesity and metabolic syndrome (MS) is important for the development of effective interventions for MS. Results: Here we show that gut microbiome mediates the preventive effect of estrogen (17β-estradiol) on metabolic endotoxemia (ME) and low-grade chronic inflammation (LGCI), the underlying causes of MS and chronic diseases. The characteristic profiles of gut microbiome observed in female and 17β-estradiol-treated male and ovariectomized mice, such as decreased Proteobacteria and lipopolysaccharide biosynthesis, were associated with a lower susceptibility to ME, LGCI, and MS in these animals. Interestingly, fecal microbiota-transplant from male mice transferred the MS phenotype to female mice, while antibiotic treatment eliminated the sexual dimorphism in MS, suggesting a causative role of the gut microbiome in this condition. Moreover, estrogenic compounds such as isoflavones exerted microbiome-modulating effects similar to those of 17β-estradiol and reversed symptoms of MS in the male mice. Finally, both expression and activity of intestinal alkaline phosphatase (IAP), a gut microbiota-modifying non-classical anti-microbial peptide, were upregulated by 17β-estradiol and isoflavones, whereas inhibition of IAP induced ME and LGCI in female mice, indicating a critical role of IAP in mediating the effects of estrogen on these parameters. Conclusions: In summary, we have identified a previously uncharacterized microbiome-based mechanism that sheds light upon sexual dimorphism in the incidence of MS and that suggests novel therapeutic targets and strategies for the management of obesity and MS in males and postmenopausal women.en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid205en
dc.identifier.citationKaliannan, K., Robertson, R.C., Murphy, K., Stanton, C., Kang, C., Wang, B., Hao, L., Bhan, A.K. and Kang, J.X., 2018. Estrogen-mediated gut microbiome alterations influence sexual dimorphism in metabolic syndrome in mice. Microbiome, 6(1): 205. DOI:10.1186/s40168-018-0587-0en
dc.identifier.doi10.1186/s40168-018-0587-0en
dc.identifier.eissn2049-2618
dc.identifier.endpage22en
dc.identifier.issued1en
dc.identifier.journaltitleMicrobiomeen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/8203
dc.identifier.volume6en
dc.language.isoenen
dc.publisherSpringer Natureen
dc.relation.urihttps://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-018-0587-0
dc.rights© 2018 The Author(s)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectEstrogenen
dc.subjectGut microbiomeen
dc.subjectObesityen
dc.subjectMetabolic syndromeen
dc.subjectIsoflavonesen
dc.subjectChronic inflammationen
dc.titleEstrogen-mediated gut microbiome alterations influence sexual dimorphism in metabolic syndrome in miceen
dc.typeArticle (peer-reviewed)en
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