{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T07:14:30Z","timestamp":1792134870949,"version":"4.4.0"},"reference-count":81,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,4,20]],"date-time":"2021-04-20T00:00:00Z","timestamp":1618876800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,4,20]],"date-time":"2021-04-20T00:00:00Z","timestamp":1618876800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013279","name":"Joint Programming Initiative A healthy diet for a healthy life","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013279","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Microbiome"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The gut microbiota\u2013intestine\u2013liver relationship is emerging as an important factor in multiple hepatic pathologies, but the hepatic sensors and effectors of microbial signals are not well defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      By comparing publicly available liver transcriptomics data from conventional vs. germ-free mice, we identified pregnane X receptor (PXR, NR1I2) transcriptional activity as strongly affected by the absence of gut microbes. Microbiota depletion using antibiotics in\n                      <jats:italic>Pxr<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>+\/+<\/jats:italic>\n                      <\/jats:sup>\n                      <jats:italic>vs Pxr<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>-\/-<\/jats:italic>\n                      <\/jats:sup>\n                      C57BL\/6J littermate mice followed by hepatic transcriptomics revealed that most microbiota-sensitive genes were PXR-dependent in the liver in males, but not in females. Pathway enrichment analysis suggested that microbiota\u2013PXR interaction controlled fatty acid and xenobiotic metabolism. We confirmed that antibiotic treatment reduced liver triglyceride content and hampered xenobiotic metabolism in the liver from\n                      <jats:italic>Pxr<\/jats:italic>\n                      <jats:sup>+\/+<\/jats:sup>\n                      but not\n                      <jats:italic>Pxr<\/jats:italic>\n                      <jats:sup>-\/-<\/jats:sup>\n                      male mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings identify PXR as a hepatic effector of microbiota-derived signals that regulate the host\u2019s sexually dimorphic lipid and xenobiotic metabolisms in the liver. Thus, our results reveal a potential new mechanism for unexpected drug\u2013drug or food\u2013drug interactions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40168-021-01050-9","type":"journal-article","created":{"date-parts":[[2021,4,20]],"date-time":"2021-04-20T10:08:13Z","timestamp":1618913293000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["The pregnane X receptor drives sexually dimorphic hepatic changes in lipid and xenobiotic metabolism in response to gut microbiota in mice"],"prefix":"10.1186","volume":"9","author":[{"given":"Sharon Ann","family":"Barretto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Lasserre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marine","family":"Huillet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"R\u00e9gnier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Polizzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannick","family":"Lippi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Fougerat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elodie","family":"Person","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Bruel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colette","family":"B\u00e9touli\u00e8res","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Naylies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Lukowicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarra","family":"Smati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Guzylack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u00efwenn","family":"Olier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassilia","family":"Th\u00e9odorou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laila","family":"Mselli-Lakhal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Zalko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Wahli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Loiseau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Gamet-Payrastre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herv\u00e9","family":"Guillou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9282-1804","authenticated-orcid":false,"given":"Sandrine","family":"Ellero-Simatos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,20]]},"reference":[{"issue":"8","key":"1050_CR1","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1210\/me.2014-1108","volume":"28","author":"G Clarke","year":"2014","unstructured":"Clarke G, Stilling RM, Kennedy PJ, Stanton C, Cryan JF, Dinan TG. Minireview: gut microbiota: the neglected endocrine organ. Mol Endocrinol. 2014;28(8):1221\u201338. https:\/\/doi.org\/10.1210\/me.2014-1108.","journal-title":"Mol Endocrinol"},{"issue":"5","key":"1050_CR2","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1016\/j.cmet.2014.07.002","volume":"20","author":"AD Patterson","year":"2014","unstructured":"Patterson AD, Turnbaugh PJ. Microbial determinants of biochemical individuality and their impact on toxicology and pharmacology. Cell Metab. 2014;20(5):761\u20138. https:\/\/doi.org\/10.1016\/j.cmet.2014.07.002.","journal-title":"Cell Metab."},{"issue":"9","key":"1050_CR3","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1016\/j.molmet.2016.06.003","volume":"5","author":"S Bashiardes","year":"2016","unstructured":"Bashiardes S, Shapiro H, Rozin S, Shibolet O, Elinav E. Non-alcoholic fatty liver and the gut microbiota. Mol Metab. 2016;5(9):782\u201394. https:\/\/doi.org\/10.1016\/j.molmet.2016.06.003.","journal-title":"Mol Metab"},{"issue":"10","key":"1050_CR4","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1038\/nm.4185","volume":"22","author":"BO Schroeder","year":"2016","unstructured":"Schroeder BO, B\u00e4ckhed F. Signals from the gut microbiota to distant organs in physiology and disease. Nat Med. 2016;22(10):1079\u201389. https:\/\/doi.org\/10.1038\/nm.4185.","journal-title":"Nat Med"},{"issue":"1","key":"1050_CR5","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1002\/hep.29466","volume":"67","author":"C Estes","year":"2018","unstructured":"Estes C, Razavi H, Loomba R, Younossi Z, Sanyal AJ. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology. 2018;67(1):123\u201333. https:\/\/doi.org\/10.1002\/hep.29466.","journal-title":"Hepatology."},{"key":"1050_CR6","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1007\/s00125-016-3902-y","volume":"59","author":"European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO)","year":"2016","unstructured":"European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. Diabetologia. 2016;59:1121\u201340.","journal-title":"Diabetologia"},{"issue":"12","key":"1050_CR7","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.1136\/gutjnl-2012-303816","volume":"62","author":"T Le Roy","year":"2012","unstructured":"Le Roy T, Llopis M, Lepage P, Bruneau A, Rabot S, Bevilacqua C, et al. Intestinal microbiota determines development of non-alcoholic fatty liver disease in mice. Gut. 2012;62(12):1787\u201394. https:\/\/doi.org\/10.1136\/gutjnl-2012-303816.","journal-title":"Gut."},{"key":"1050_CR8","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1002\/hep.26319","volume":"58","author":"M Mouzaki","year":"2013","unstructured":"Mouzaki M, Comelli EM, Arendt BM, Bonengel J, Fung SK, Fischer SE, et al. Intestinal microbiota in patients with nonalcoholic fatty liver disease. Hepatology. 2013;58:120\u20137.","journal-title":"Hepatology"},{"issue":"2","key":"1050_CR9","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1002\/hep.26093","volume":"57","author":"L Zhu","year":"2013","unstructured":"Zhu L, Baker SS, Gill C, Liu W, Alkhouri R, Baker RD, et al. Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: a connection between endogenous alcohol and NASH. Hepatology. 2013;57(2):601\u20139. https:\/\/doi.org\/10.1002\/hep.26093.","journal-title":"Hepatology."},{"issue":"7","key":"1050_CR10","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1038\/s41591-018-0061-3","volume":"24","author":"L Hoyles","year":"2018","unstructured":"Hoyles L, Fern\u00e1ndez-Real J-M, Federici M, Serino M, Abbott J, Charpentier J, et al. Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women. Nat Med. 2018;24(7):1070\u201380. https:\/\/doi.org\/10.1038\/s41591-018-0061-3.","journal-title":"Nat Med"},{"issue":"1","key":"1050_CR11","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1172\/JCI76738","volume":"125","author":"C Jiang","year":"2015","unstructured":"Jiang C, Xie C, Li F, Zhang L, Nichols RG, Krausz KW, et al. Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease. J Clin Invest. 2015;125(1):386\u2013402. https:\/\/doi.org\/10.1172\/JCI76738.","journal-title":"J Clin Invest"},{"issue":"1","key":"1050_CR12","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1079\/NRR200498","volume":"18","author":"GS Stewart","year":"2005","unstructured":"Stewart GS, Smith CP. Urea nitrogen salvage mechanisms and their relevance to ruminants, non-ruminants and man. Nutr Res Rev. 2005;18(1):49\u201362. https:\/\/doi.org\/10.1079\/NRR200498.","journal-title":"Nutr Res Rev"},{"issue":"7341","key":"1050_CR13","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/nature09922","volume":"472","author":"Z Wang","year":"2011","unstructured":"Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison B, DuGar B, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011;472(7341):57\u201365. https:\/\/doi.org\/10.1038\/nature09922.","journal-title":"Nature."},{"issue":"5","key":"1050_CR14","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1016\/j.cmet.2020.03.006","volume":"31","author":"BJ Saeedi","year":"2020","unstructured":"Saeedi BJ, Liu KH, Owens JA, Hunter-Chang S, Camacho MC, Eboka RU, et al. Gut-resident Lactobacilli activate hepatic Nrf2 and protect against oxidative liver injury. Cell Metab. 2020;31(5):956\u2013968.e5. https:\/\/doi.org\/10.1016\/j.cmet.2020.03.006.","journal-title":"Cell Metab"},{"key":"1050_CR15","doi-asserted-by":"publisher","first-page":"3760","DOI":"10.1038\/s41467-018-05767-4","volume":"9","author":"A Kindt","year":"2018","unstructured":"Kindt A, Liebisch G, Clavel T, Haller D, H\u00f6rmannsperger G, Yoon H, et al. The gut microbiota promotes hepatic fatty acid desaturation and elongation in mice. Nat Commun. Nature. 2018;9:3760.","journal-title":"Nat Commun. Nature"},{"issue":"2","key":"1050_CR16","doi-asserted-by":"publisher","first-page":"e00271","DOI":"10.1128\/mBio.00271-10","volume":"2","author":"SP Claus","year":"2011","unstructured":"Claus SP, Ellero SL, Berger B, Krause L, Bruttin A, Molina J, et al. Colonization-induced host-gut microbial metabolic interaction. MBio. 2011;2(2):e00271\u201310. https:\/\/doi.org\/10.1128\/mBio.00271-10.","journal-title":"MBio."},{"issue":"1","key":"1050_CR17","doi-asserted-by":"publisher","first-page":"20127","DOI":"10.1038\/srep20127","volume":"6","author":"A Montagner","year":"2016","unstructured":"Montagner A, Korecka A, Polizzi A, Lippi Y, Blum Y, Canlet C, et al. Hepatic circadian clock oscillators and nuclear receptors integrate microbiome-derived signals. Sci Rep. 2016;6(1):20127. https:\/\/doi.org\/10.1038\/srep20127.","journal-title":"Sci Rep"},{"issue":"12","key":"1050_CR18","doi-asserted-by":"publisher","first-page":"2035","DOI":"10.1136\/gutjnl-2016-312729","volume":"65","author":"H Tilg","year":"2016","unstructured":"Tilg H, Cani PD, Mayer EA. Gut microbiome and liver diseases. Gut. 2016;65(12):2035\u201344. https:\/\/doi.org\/10.1136\/gutjnl-2016-312729.","journal-title":"Gut."},{"issue":"3","key":"1050_CR19","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/j.jhepr.2019.04.004","volume":"1","author":"KJ Schwenger","year":"2019","unstructured":"Schwenger KJ, Clermont-Dejean N, Allard JP. The role of the gut microbiome in chronic liver disease: the clinical evidence revised. JHEP Reports. 2019;1(3):214\u201326. https:\/\/doi.org\/10.1016\/j.jhepr.2019.04.004.","journal-title":"JHEP Reports"},{"issue":"6","key":"1050_CR20","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1016\/j.jhep.2019.08.005","volume":"71","author":"J Mouries","year":"2019","unstructured":"Mouries J, Brescia P, Silvestri A, Spadoni I, Sorribas M, Wiest R, et al. Microbiota-driven gut vascular barrier disruption is a prerequisite for non-alcoholic steatohepatitis development. J Hepatol. 2019;71(6):1216\u201328. https:\/\/doi.org\/10.1016\/j.jhep.2019.08.005.","journal-title":"J Hepatol"},{"key":"1050_CR21","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.2337\/db06-1491","volume":"56","author":"PD Cani","year":"2007","unstructured":"Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007;56:1761\u201372.","journal-title":"Diabetes"},{"key":"1050_CR22","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1038\/nature10809","volume":"482","author":"J Henao-Mejia","year":"2012","unstructured":"Henao-Mejia J, Elinav E, Jin C, Hao L, Mehal WZ, Strowig T, et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature. 2012;482:179\u201385.","journal-title":"Nature"},{"key":"1050_CR23","doi-asserted-by":"publisher","first-page":"3760","DOI":"10.1038\/s41467-018-05767-4","volume":"9","author":"A Kindt","year":"2018","unstructured":"Kindt A, Liebisch G, Clavel T, Haller D, H\u00f6rmannsperger G, Yoon H, et al. The gut microbiota promotes hepatic fatty acid desaturation and elongation in mice. Nat Commun. 2018;9:3760.","journal-title":"Nat Commun"},{"issue":"4","key":"1050_CR24","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1016\/j.celrep.2018.03.109","volume":"23","author":"S Krishnan","year":"2018","unstructured":"Krishnan S, Ding Y, Saedi N, Choi M, Sridharan GV, Sherr DH, et al. Gut microbiota-derived tryptophan metabolites modulate inflammatory response in hepatocytes and macrophages. Cell Rep. 2018;23(4):1099\u2013111. https:\/\/doi.org\/10.1016\/j.celrep.2018.03.109.","journal-title":"Cell Rep"},{"issue":"1","key":"1050_CR25","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/j.celrep.2017.06.039","volume":"20","author":"M-E Dumas","year":"2017","unstructured":"Dumas M-E, Rothwell AR, Hoyles L, Aranias T, Chilloux J, Calderari S, et al. Microbial-host co-metabolites are prodromal markers predicting phenotypic heterogeneity in behavior, obesity, and impaired glucose tolerance. Cell Rep. 2017;20(1):136\u201348. https:\/\/doi.org\/10.1016\/j.celrep.2017.06.039.","journal-title":"Cell Rep"},{"issue":"2","key":"1050_CR26","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.immuni.2014.06.014","volume":"41","author":"M Venkatesh","year":"2014","unstructured":"Venkatesh M, Mukherjee S, Wang H, Li H, Sun K, Benechet AP, et al. Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4. Immunity. 2014;41(2):296\u2013310. https:\/\/doi.org\/10.1016\/j.immuni.2014.06.014.","journal-title":"Immunity."},{"issue":"6","key":"1050_CR27","doi-asserted-by":"publisher","first-page":"3369","DOI":"10.1073\/pnas.051551698","volume":"98","author":"JL Staudinger","year":"2001","unstructured":"Staudinger JL, Goodwin B, Jones SA, Hawkins-Brown D, MacKenzie KI, LaTour A, et al. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc Natl Acad Sci U S A. 2001;98(6):3369\u201374. https:\/\/doi.org\/10.1073\/pnas.051551698.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7","key":"1050_CR28","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1136\/gutjnl-2014-309059","volume":"65","author":"KA Knoop","year":"2015","unstructured":"Knoop KA, McDonald KG, Kulkarni DH, Newberry RD. Antibiotics promote inflammation through the translocation of native commensal colonic bacteria. Gut. 2015;65(7):1100\u20139. https:\/\/doi.org\/10.1136\/gutjnl-2014-309059.","journal-title":"Gut."},{"key":"1050_CR29","doi-asserted-by":"publisher","first-page":"7126","DOI":"10.1096\/fj.201801526RR","volume":"33","author":"X Zhang","year":"2019","unstructured":"Zhang X, Grosfeld A, Williams E, Vasiliauskas D, Barretto S, Smith L, et al. Fructose malabsorption induces cholecystokinin expression in the ileum and cecum by changing microbiota composition and metabolism. FASEB J. 2019;33:7126\u201342.","journal-title":"FASEB J"},{"key":"1050_CR30","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0142334","volume":"10","author":"J Lluch","year":"2015","unstructured":"Lluch J, Servant F, Pa\u00efss\u00e9 S, Valle C, Vali\u00e8re S, Kuchly C, et al. The characterization of novel tissue microbiota using an optimized 16S metagenomic sequencing pipeline. Heimesaat MM, editor. PLoS One. 2015;10:e0142334.","journal-title":"PLoS One"},{"issue":"8","key":"1050_CR31","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1093\/bioinformatics\/btx791","volume":"34","author":"F Escudi\u00e9","year":"2018","unstructured":"Escudi\u00e9 F, Auer L, Bernard M, Mariadassou M, Cauquil L, Vidal K, et al. FROGS: Find, Rapidly, OTUs with Galaxy Solution. Berger B, editor. Bioinformatics. 2018;34(8):1287\u201394. https:\/\/doi.org\/10.1093\/bioinformatics\/btx791.","journal-title":"Bioinformatics."},{"key":"1050_CR32","unstructured":"Lowry OH, Rosebrough NJ, biological AFJO. Protein measurement with the Folin phenol reagent. cabdirect.org. 1951;193(1):265\u201375."},{"key":"1050_CR33","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/j.cels.2018.10.007","volume":"7","author":"D Torre","year":"2018","unstructured":"Torre D, Lachmann A, Ma\u2019ayan A. BioJupies: automated generation of interactive notebooks for RNA-Seq data analysis in the Cloud. Cell Syst. 2018;7:556\u201361 e3.","journal-title":"Cell Syst"},{"issue":"W1","key":"1050_CR34","doi-asserted-by":"publisher","first-page":"W90","DOI":"10.1093\/nar\/gkw377","volume":"44","author":"MV Kuleshov","year":"2016","unstructured":"Kuleshov MV, Jones MR, Rouillard AD, Fernandez NF, Duan Q, Wang Z, et al. Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res. 2016;44(W1):W90\u20137. https:\/\/doi.org\/10.1093\/nar\/gkw377.","journal-title":"Nucleic Acids Res"},{"key":"1050_CR35","doi-asserted-by":"publisher","first-page":"18898","DOI":"10.1038\/srep18898","volume":"6","author":"L Cheng","year":"2016","unstructured":"Cheng L, Lo L-Y, NLS T, Wang D, Leung K-S. CrossNorm: a novel normalization strategy for microarray data in cancers. Sci Rep. 2016;6:18898.","journal-title":"Sci Rep"},{"key":"1050_CR36","doi-asserted-by":"crossref","unstructured":"Smyth GK. Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol. 2004;3:Article3\u201325.","DOI":"10.2202\/1544-6115.1027"},{"issue":"17","key":"1050_CR37","doi-asserted-by":"publisher","first-page":"3055","DOI":"10.1093\/bioinformatics\/bty1054","volume":"35","author":"A Singh","year":"2019","unstructured":"Singh A, Shannon CP, Gautier B, Rohart F, Vacher M, Tebbutt SJ, et al. DIABLO: an integrative approach for identifying key molecular drivers from multi-omics assays. Birol I, editor. Bioinformatics. 2019;35(17):3055\u201362. https:\/\/doi.org\/10.1093\/bioinformatics\/bty1054.","journal-title":"Bioinformatics."},{"issue":"21","key":"1050_CR38","doi-asserted-by":"publisher","first-page":"2855","DOI":"10.1093\/bioinformatics\/btp515","volume":"25","author":"K-A L\u00ea Cao","year":"2009","unstructured":"L\u00ea Cao K-A, Gonz\u00e1lez I, D\u00e9jean S. integrOmics: an R package to unravel relationships between two omics datasets. Bioinformatics. 2009;25(21):2855\u20136. https:\/\/doi.org\/10.1093\/bioinformatics\/btp515.","journal-title":"Bioinformatics."},{"key":"1050_CR39","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/S0092-8674(00)80726-6","volume":"97","author":"Nuclear Receptors Nomenclature Committee","year":"1999","unstructured":"Nuclear Receptors Nomenclature Committee. A unified nomenclature system for the nuclear receptor superfamily. Cell. 1999;97:161\u20133.","journal-title":"Cell."},{"issue":"1","key":"1050_CR40","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/S0092-8674(00)80900-9","volume":"92","author":"SA Kliewer","year":"1998","unstructured":"Kliewer SA, Moore JT, Wade L, Staudinger JL, Watson MA, Jones SA, et al. An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell. 1998;92(1):73\u201382. https:\/\/doi.org\/10.1016\/S0092-8674(00)80900-9.","journal-title":"Cell."},{"key":"1050_CR41","doi-asserted-by":"publisher","first-page":"1268","DOI":"10.1210\/me.2002-0421","volume":"17","author":"JM Rosenfeld","year":"2003","unstructured":"Rosenfeld JM, Vargas R, Xie W, Evans RM. Genetic profiling defines the xenobiotic gene network controlled by the nuclear receptor pregnane X receptor. Mol Endocrinol. 2003;17:1268\u201382. https:\/\/doi.org\/10.1210\/me.2002-0421.","journal-title":"Mol Endocrinol."},{"issue":"12","key":"1050_CR42","doi-asserted-by":"publisher","first-page":"107795","DOI":"10.1016\/j.celrep.2020.107795","volume":"31","author":"CM Lopes-Ramos","year":"2020","unstructured":"Lopes-Ramos CM, Chen C-Y, Kuijjer ML, Paulson JN, Sonawane AR, Fagny M, et al. Sex differences in gene expression and regulatory networks across 29 human tissues. Cell Rep. 2020;31(12):107795. https:\/\/doi.org\/10.1016\/j.celrep.2020.107795.","journal-title":"Cell Rep"},{"key":"1050_CR43","doi-asserted-by":"publisher","unstructured":"Weger BD, Gobet C, Yeung J, Martin E, Jimenez S, Betrisey B, et al. The mouse microbiome is required for sex-specific diurnal rhythms of gene expression and metabolism. Cell Metab. 2019;29(2):362\u201382.e8. https:\/\/doi.org\/10.1016\/j.cmet.2018.09.023.","DOI":"10.1016\/j.cmet.2018.09.023"},{"issue":"9","key":"1050_CR44","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.3109\/07420528.2013.805762","volume":"30","author":"Y-F Lu","year":"2013","unstructured":"Lu Y-F, Jin T, Xu Y, Zhang D, Wu Q, Zhang Y-KJ, et al. Sex differences in the circadian variation of cytochrome p450 genes and corresponding nuclear receptors in mouse liver. Chronobiol Int. 2013;30(9):1135\u201343. https:\/\/doi.org\/10.3109\/07420528.2013.805762.","journal-title":"Chronobiol Int"},{"key":"1050_CR45","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1152\/physrev.00025.2005","volume":"86","author":"B Desvergne","year":"2006","unstructured":"Desvergne B, Michalik L, Wahli W. Transcriptional regulation of metabolism. Physiol Rev. 2006;86:465\u2013514.","journal-title":"Physiol Rev"},{"issue":"4","key":"1050_CR46","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1016\/j.cell.2006.06.049","volume":"126","author":"AL Bookout","year":"2006","unstructured":"Bookout AL, Jeong Y, Downes M, Yu RT, Evans RM, Mangelsdorf DJ. Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network. Cell. 2006;126(4):789\u201399. https:\/\/doi.org\/10.1016\/j.cell.2006.06.049.","journal-title":"Cell."},{"issue":"4","key":"1050_CR47","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1002\/hep.1840380424","volume":"38","author":"R Wolbold","year":"2003","unstructured":"Wolbold R, Klein K, Burk O, N\u00fcssler AK, Neuhaus P, Eichelbaum M, et al. Sex is a major determinant of CYP3A4 expression in human liver. Hepatology. 2003;38(4):978\u201388. https:\/\/doi.org\/10.1002\/hep.1840380424.","journal-title":"Hepatology."},{"issue":"3","key":"1050_CR48","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1124\/jpet.115.224295","volume":"354","author":"K Spruiell","year":"2015","unstructured":"Spruiell K, Gyamfi AA, Yeyeodu ST, Richardson RM, Gonzalez FJ, Gyamfi MA. Pregnane X receptor-humanized mice recapitulate gender differences in ethanol metabolism but not hepatotoxicity. J Pharmacol Exp Ther. 2015;354(3):459\u201370. https:\/\/doi.org\/10.1124\/jpet.115.224295.","journal-title":"J Pharmacol Exp Ther"},{"issue":"10","key":"1050_CR49","doi-asserted-by":"publisher","first-page":"3138","DOI":"10.1172\/JCI39019","volume":"119","author":"N Leuenberger","year":"2009","unstructured":"Leuenberger N, Pradervand S, Wahli W. Sumoylated PPARalpha mediates sex-specific gene repression and protects the liver from estrogen-induced toxicity in mice. J Clin Invest. 2009;119(10):3138\u201348. https:\/\/doi.org\/10.1172\/JCI39019.","journal-title":"J Clin Invest"},{"key":"1050_CR50","first-page":"1170","volume":"2016","author":"W Cui","year":"1859","unstructured":"Cui W, Sun M, Zhang S, Shen X, Galeva N, Williams TD, et al. A SUMO-acetyl switch in PXR biology. Biochim Biophys Acta. 1859;2016:1170\u201382.","journal-title":"Biochim Biophys Acta"},{"key":"1050_CR51","unstructured":"Pramfalk C, Pavlides M, Banerjee R, McNeil CA, Neubauer S, Karpe F, et al. Sex-specific differences in hepatic fat oxidation and synthesis may explain the higher propensity for NAFLD in men. J Clin Endocrinol Metab. 2015 ed. 2015;100:4425\u201333."},{"key":"1050_CR52","doi-asserted-by":"publisher","first-page":"1291","DOI":"10.1007\/s12325-017-0556-1","volume":"34","author":"S Ballestri","year":"2017","unstructured":"Ballestri S, Nascimbeni F, Baldelli E, Marrazzo A, Romagnoli D, Lonardo A. NAFLD as a sexual dimorphic disease: role of gender and reproductive status in the development and progression of nonalcoholic fatty liver disease and inherent cardiovascular risk. Adv Ther. 2017;34:1291\u2013326.","journal-title":"Adv Ther"},{"key":"1050_CR53","doi-asserted-by":"crossref","unstructured":"El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012;142:1264\u20131273.e1.","DOI":"10.1053\/j.gastro.2011.12.061"},{"key":"1050_CR54","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.tox.2016.10.006","volume":"373","author":"D Hanna","year":"2016","unstructured":"Hanna D, Riedmaier AE, Sugamori KS, Grant DM. Influence of sex and developmental stage on acute hepatotoxic and inflammatory responses to liver procarcinogens in the mouse. Toxicology. 2016;373:30\u201340. https:\/\/doi.org\/10.1016\/j.tox.2016.10.006.","journal-title":"Toxicology."},{"issue":"1","key":"1050_CR55","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1034\/j.1600-0676.2003.00811.x","volume":"23","author":"I Shimizu","year":"2003","unstructured":"Shimizu I. Impact of oestrogens on the progression of liver disease. Liver Int. 2003;23(1):63\u20139. https:\/\/doi.org\/10.1034\/j.1600-0676.2003.00811.x.","journal-title":"Liver Int"},{"key":"1050_CR56","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1038\/384039a0","volume":"384","author":"PR Devchand","year":"1996","unstructured":"Devchand PR, Keller H, Peters JM, Vazquez M, Gonzalez FJ, Wahli W. The PPARalpha-leukotriene B4 pathway to inflammation control. Nature. 1996;384:39\u201343.","journal-title":"Nature"},{"issue":"8","key":"1050_CR57","doi-asserted-by":"publisher","first-page":"2280","DOI":"10.1172\/JCI26283","volume":"116","author":"C Zhou","year":"2006","unstructured":"Zhou C, Tabb MM, Nelson EL, Gr\u00fcn F, Verma S, Sadatrafiei A, et al. Mutual repression between steroid and xenobiotic receptor and NF-kappaB signaling pathways links xenobiotic metabolism and inflammation. J Clin Invest. 2006;116(8):2280\u20139. https:\/\/doi.org\/10.1172\/JCI26283.","journal-title":"J Clin Invest"},{"issue":"9","key":"1050_CR58","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006958","volume":"4","author":"B Bj\u00f6rkholm","year":"2009","unstructured":"Bj\u00f6rkholm B, Bok CM, Lundin A, Rafter J, Hibberd ML, Pettersson S. Intestinal microbiota regulate xenobiotic metabolism in the liver. PLoS One. 2009;4(9):e6958. https:\/\/doi.org\/10.1371\/journal.pone.0006958.","journal-title":"PLoS One"},{"issue":"10","key":"1050_CR59","doi-asserted-by":"publisher","first-page":"834","DOI":"10.15252\/msb.20156487","volume":"11","author":"A Mardinoglu","year":"2015","unstructured":"Mardinoglu A, Shoaie S, Bergentall M, Ghaffari P, Zhang C, Larsson E, et al. The gut microbiota modulates host amino acid and glutathione metabolism in mice. Mol Syst Biol. 2015;11(10):834. https:\/\/doi.org\/10.15252\/msb.20156487.","journal-title":"Mol Syst Biol"},{"issue":"1","key":"1050_CR60","doi-asserted-by":"publisher","first-page":"2408","DOI":"10.1038\/s41467-019-10440-5","volume":"10","author":"Y Min","year":"2019","unstructured":"Min Y, Ma X, Sankaran K, Ru Y, Chen L, Baiocchi M, et al. Sex-specific association between gut microbiome and fat distribution. Nat Commun. 2019;10(1):2408\u20139. https:\/\/doi.org\/10.1038\/s41467-019-10440-5.","journal-title":"Nat Commun"},{"key":"1050_CR61","first-page":"728","volume":"13","author":"J Wang","year":"2014","unstructured":"Wang J, Dai S, Guo Y, Xie W, Zhai Y. Biology of PXR: role in drug-hormone interactions. EXCLI J. 2014;13:728\u201339.","journal-title":"EXCLI J."},{"issue":"12","key":"1050_CR62","doi-asserted-by":"publisher","first-page":"5721","DOI":"10.1210\/en.2010-0708","volume":"151","author":"B Zhang","year":"2010","unstructured":"Zhang B, Cheng Q, Ou Z, Lee JH, Xu M, Kochhar U, et al. Pregnane X receptor as a therapeutic target to inhibit androgen activity. Endocrinology. 2010;151(12):5721\u20139. https:\/\/doi.org\/10.1210\/en.2010-0708.","journal-title":"Endocrinology."},{"issue":"19","key":"1050_CR63","doi-asserted-by":"publisher","first-page":"8392","DOI":"10.1093\/nar\/gkr458","volume":"39","author":"S Kodama","year":"2011","unstructured":"Kodama S, Hosseinpour F, Goldstein JA, Negishi M. Liganded pregnane X receptor represses the human sulfotransferase SULT1E1 promoter through disrupting its chromatin structure. Nucleic Acids Res. 2011;39(19):8392\u2013403. https:\/\/doi.org\/10.1093\/nar\/gkr458.","journal-title":"Nucleic Acids Res"},{"issue":"8","key":"1050_CR64","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1136\/gutjnl-2011-301104","volume":"61","author":"E Larsson","year":"2012","unstructured":"Larsson E, Tremaroli V, Lee YS, Koren O, Nookaew I, Fricker A, et al. Analysis of gut microbial regulation of host gene expression along the length of the gut and regulation of gut microbial ecology through MyD88. Gut. 2012;61(8):1124\u201331. https:\/\/doi.org\/10.1136\/gutjnl-2011-301104.","journal-title":"Gut."},{"issue":"6","key":"1050_CR65","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1016\/j.cmet.2015.09.028","volume":"22","author":"V Singh","year":"2015","unstructured":"Singh V, Chassaing B, Zhang L, San Yeoh B, Xiao X, Kumar M, et al. Microbiota-dependent hepatic lipogenesis mediated by stearoyl CoA desaturase 1 (SCD1) promotes metabolic syndrome in TLR5-deficient mice. Cell Metab. 2015;22(6):983\u201396. https:\/\/doi.org\/10.1016\/j.cmet.2015.09.028.","journal-title":"Cell Metab"},{"issue":"12","key":"1050_CR66","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.1124\/dmd.117.077313","volume":"45","author":"ZD Fu","year":"2017","unstructured":"Fu ZD, Selwyn FP, Cui JY, Klaassen CD. RNA-Seq profiling of intestinal expression of xenobiotic processing genes in germ-free mice. Drug Metab Dispos. 2017;45(12):1225\u201338. https:\/\/doi.org\/10.1124\/dmd.117.077313.","journal-title":"Drug Metab Dispos"},{"issue":"6344","key":"1050_CR67","doi-asserted-by":"publisher","first-page":"eaag2770","DOI":"10.1126\/science.aag2770","volume":"356","author":"N Koppel","year":"2017","unstructured":"Koppel N, Maini Rekdal V, Balskus EP. Chemical transformation of xenobiotics by the human gut microbiota. Science. 2017;356(6344):eaag2770. https:\/\/doi.org\/10.1126\/science.aag2770.","journal-title":"Science."},{"issue":"10","key":"1050_CR68","doi-asserted-by":"publisher","first-page":"4173","DOI":"10.1172\/JCI72335","volume":"124","author":"RN Carmody","year":"2014","unstructured":"Carmody RN, Turnbaugh PJ. Host-microbial interactions in the metabolism of therapeutic and diet-derived xenobiotics. J Clin Invest. 2014;124(10):4173\u201381. https:\/\/doi.org\/10.1172\/JCI72335.","journal-title":"J Clin Invest"},{"key":"1050_CR69","first-page":"1","volume":"2","author":"SP Claus","year":"2016","unstructured":"Claus SP, Guillou H, Ellero-Simatos S. The gut microbiota: a major player in the toxicity of environmental pollutants? npj Biofilms and Microbiomes. Nature Publishing Group. 2016;2:1\u201311.","journal-title":"Nature Publishing Group"},{"issue":"2","key":"1050_CR70","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1124\/dmd.115.067504","volume":"44","author":"FP Selwyn","year":"2016","unstructured":"Selwyn FP, Cheng SL, Klaassen CD, Cui JY. Regulation of hepatic drug-metabolizing enzymes in germ-free mice by conventionalization and probiotics. Drug Metab Dispos. 2016;44(2):262\u201374. https:\/\/doi.org\/10.1124\/dmd.115.067504.","journal-title":"Drug Metab Dispos"},{"key":"1050_CR71","doi-asserted-by":"publisher","unstructured":"Yu J, Petrie ID, Levy RH, Ragueneau-Majlessi I. Mechanisms and clinical significance of pharmacokinetic-based drug-drug interactions with drugs approved by the U.S. Food and Drug Administration in 2017. Drug Metab. Dispos. 2019;47(2):135\u201344. https:\/\/doi.org\/10.1124\/dmd.118.084905.","DOI":"10.1124\/dmd.118.084905"},{"issue":"1","key":"1050_CR72","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1124\/dmd.116.072025","volume":"45","author":"BC Jones","year":"2017","unstructured":"Jones BC, Rollison H, Johansson S, Kanebratt KP, Lambert C, Vishwanathan K, et al. Managing the risk of CYP3A induction in drug development: a strategic approach. Drug Metab Dispos. 2017;45(1):35\u201341. https:\/\/doi.org\/10.1124\/dmd.116.072025.","journal-title":"Drug Metab Dispos"},{"issue":"4","key":"1050_CR73","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1002\/cpt.525","volume":"101","author":"T Prueksaritanont","year":"2017","unstructured":"Prueksaritanont T, Tatosian DA, Chu X, Railkar R, Evers R, Chavez-Eng C, et al. Validation of a microdose probe drug cocktail for clinical drug interaction assessments for drug transporters and CYP3A. Clin Pharmacol Therapeutics. 2017;101(4):519\u201330. https:\/\/doi.org\/10.1002\/cpt.525.","journal-title":"Clin Pharmacol Therapeutics"},{"issue":"7521","key":"1050_CR74","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/nature13793","volume":"514","author":"J Suez","year":"2014","unstructured":"Suez J, Korem T, Zeevi D, Zilberman-Schapira G, Thaiss CA, Maza O, et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014;514(7521):181\u20136. https:\/\/doi.org\/10.1038\/nature13793.","journal-title":"Nature."},{"key":"1050_CR75","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1038\/nature14232","volume":"519","author":"B Chassaing","year":"2015","unstructured":"Chassaing B, Koren O, Goodrich JK, Poole AC, Srinivasan S, Ley RE, et al. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature. 2015;519:92\u20136.","journal-title":"Nature"},{"key":"1050_CR76","doi-asserted-by":"publisher","unstructured":"Ranhotra HS, Flannigan KL, Brave M, Mukherjee S, Lukin DJ, Hirota SA, et al. Xenobiotic receptor-mediated regulation of intestinal barrier function and innate immunity. Nucl Receptor Res. 2016;3. https:\/\/doi.org\/10.11131\/2016\/101199.","DOI":"10.11131\/2016\/101199"},{"key":"1050_CR77","doi-asserted-by":"publisher","first-page":"E350","DOI":"10.1152\/ajpendo.00572.2018","volume":"317","author":"VKP Venu","year":"2019","unstructured":"Venu VKP, Saifeddine M, Mihara K, Tsai Y-C, Nieves K, Alston L, et al. The pregnane X receptor and its microbiota-derived ligand indole 3-propionic acid regulate endothelium-dependent vasodilation. Am J Physiol Endocrinol Metab. 2019;317:E350\u201361.","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"7","key":"1050_CR78","doi-asserted-by":"publisher","first-page":"1720","DOI":"10.1210\/me.2004-0427","volume":"19","author":"MD Krasowski","year":"2005","unstructured":"Krasowski MD, Yasuda K, Hagey LR, Schuetz EG. Evolution of the pregnane x receptor: adaptation to cross-species differences in biliary bile salts. Mol Endocrinol. 2005;19(7):1720\u201339. https:\/\/doi.org\/10.1210\/me.2004-0427.","journal-title":"Mol Endocrinol"},{"key":"1050_CR79","doi-asserted-by":"publisher","first-page":"19081","DOI":"10.1074\/jbc.M600116200","volume":"281","author":"D Jung","year":"2006","unstructured":"Jung D, Mangelsdorf DJ, Meyer UA. Pregnane X receptor is a target of farnesoid X receptor. J Biol Chem. 2006;281:19081\u201391.","journal-title":"J Biol Chem"},{"key":"1050_CR80","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1194\/jlr.M600282-JLR200","volume":"48","author":"T Li","year":"2007","unstructured":"Li T, Chen W, Chiang JYL. PXR induces CYP27A1 and regulates cholesterol metabolism in the intestine. J Lipid Res. 2007;48:373\u201384.","journal-title":"J Lipid Res"},{"issue":"1","key":"1050_CR81","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1038\/nrgastro.2013.151","volume":"11","author":"FG Schaap","year":"2014","unstructured":"Schaap FG, Trauner M, Jansen PLM. Bile acid receptors as targets for drug development. Nat Rev Gastroenterol Hepatol. 2014;11(1):55\u201367. https:\/\/doi.org\/10.1038\/nrgastro.2013.151.","journal-title":"Nat Rev Gastroenterol Hepatol"}],"container-title":["Microbiome"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40168-021-01050-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40168-021-01050-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40168-021-01050-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T00:03:11Z","timestamp":1634256191000},"score":1,"resource":{"primary":{"URL":"https:\/\/microbiomejournal.biomedcentral.com\/articles\/10.1186\/s40168-021-01050-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,20]]},"references-count":81,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1050"],"URL":"https:\/\/doi.org\/10.1186\/s40168-021-01050-9","relation":{},"ISSN":["2049-2618"],"issn-type":[{"value":"2049-2618","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,20]]},"assertion":[{"value":"2 February 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 March 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 April 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All experiments involving mice were performed in a conventional laboratory animal room following the European Union guidelines for laboratory animal use and care. The project was approved by an independent ethics committee (CEEA-86 Toxcom\u00e9thique) under the authorization number 2018062810452910. The animals were treated humanely with due consideration to the alleviation of distress and discomfort.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"93"}}