Aryl Hydrocarbon Receptor (AhR) Activation by 2,3,7,8-Tetrachlorodibenzo-<i>p</i>-Dioxin (TCDD) Dose-Dependently Shifts the Gut Microbiome Consistent with the Progression of Non-Alcoholic Fatty Liver Disease

Gut dysbiosis with disrupted enterohepatic bile acid metabolism is commonly associated with non-alcoholic fatty liver disease (NAFLD) and recapitulated in a NAFLD-phenotype elicited by 2,3,7,8-tetrachlorodibenzo-<i>p</i>-dioxin (TCDD) in mice. TCDD induces hepatic fat accumulation and in...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Russell R. Fling, Timothy R. Zacharewski
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	2,3,7,8-tetrachlorodibenzo-<i>p</i>-dioxin dioxin aryl hydrocarbon receptor non-alcoholic fatty liver disease gut microbiome fibrosis Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/41119752f628489ea5a9b3ddd7de6fcb
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:41119752f628489ea5a9b3ddd7de6fcb
record_format	dspace
spelling	oai:doaj.org-article:41119752f628489ea5a9b3ddd7de6fcb2021-11-25T17:56:34ZAryl Hydrocarbon Receptor (AhR) Activation by 2,3,7,8-Tetrachlorodibenzo-<i>p</i>-Dioxin (TCDD) Dose-Dependently Shifts the Gut Microbiome Consistent with the Progression of Non-Alcoholic Fatty Liver Disease10.3390/ijms2222124311422-00671661-6596https://doaj.org/article/41119752f628489ea5a9b3ddd7de6fcb2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12431https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Gut dysbiosis with disrupted enterohepatic bile acid metabolism is commonly associated with non-alcoholic fatty liver disease (NAFLD) and recapitulated in a NAFLD-phenotype elicited by 2,3,7,8-tetrachlorodibenzo-<i>p</i>-dioxin (TCDD) in mice. TCDD induces hepatic fat accumulation and increases levels of secondary bile acids, including taurolithocholic acid and deoxycholic acid (microbial modified bile acids involved in host bile acid regulation signaling pathways). To investigate the effects of TCDD on the gut microbiota, the cecum contents of male C57BL/6 mice orally gavaged with sesame oil vehicle or 0.3, 3, or 30 µg/kg TCDD were examined using shotgun metagenomic sequencing. Taxonomic analysis identified dose-dependent increases in Lactobacillus species (i.e., <i>Lactobacillus reuteri</i>). Increased species were also associated with dose-dependent increases in bile salt hydrolase sequences, responsible for deconjugation reactions in secondary bile acid metabolism. Increased <i>L. reuteri</i> levels were further associated with mevalonate-dependent isopentenyl diphosphate (IPP) biosynthesis and o-succinylbenzoate synthase, a menaquinone biosynthesis associated gene. Analysis of the gut microbiomes from cirrhosis patients identified an increased abundance of genes from the mevalonate-dependent IPP biosynthesis as well as several other menaquinone biosynthesis genes, including o-succinylbenzoate synthase. These results extend the association of lactobacilli with the AhR/intestinal axis in NAFLD progression and highlight the similarities between TCDD-elicited phenotypes in mice to human NAFLD.Russell R. FlingTimothy R. ZacharewskiMDPI AGarticle2,3,7,8-tetrachlorodibenzo-<i>p</i>-dioxindioxinaryl hydrocarbon receptornon-alcoholic fatty liver diseasegut microbiomefibrosisBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12431, p 12431 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	2,3,7,8-tetrachlorodibenzo-<i>p</i>-dioxin dioxin aryl hydrocarbon receptor non-alcoholic fatty liver disease gut microbiome fibrosis Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	2,3,7,8-tetrachlorodibenzo-<i>p</i>-dioxin dioxin aryl hydrocarbon receptor non-alcoholic fatty liver disease gut microbiome fibrosis Biology (General) QH301-705.5 Chemistry QD1-999 Russell R. Fling Timothy R. Zacharewski Aryl Hydrocarbon Receptor (AhR) Activation by 2,3,7,8-Tetrachlorodibenzo-<i>p</i>-Dioxin (TCDD) Dose-Dependently Shifts the Gut Microbiome Consistent with the Progression of Non-Alcoholic Fatty Liver Disease
description	Gut dysbiosis with disrupted enterohepatic bile acid metabolism is commonly associated with non-alcoholic fatty liver disease (NAFLD) and recapitulated in a NAFLD-phenotype elicited by 2,3,7,8-tetrachlorodibenzo-<i>p</i>-dioxin (TCDD) in mice. TCDD induces hepatic fat accumulation and increases levels of secondary bile acids, including taurolithocholic acid and deoxycholic acid (microbial modified bile acids involved in host bile acid regulation signaling pathways). To investigate the effects of TCDD on the gut microbiota, the cecum contents of male C57BL/6 mice orally gavaged with sesame oil vehicle or 0.3, 3, or 30 µg/kg TCDD were examined using shotgun metagenomic sequencing. Taxonomic analysis identified dose-dependent increases in Lactobacillus species (i.e., <i>Lactobacillus reuteri</i>). Increased species were also associated with dose-dependent increases in bile salt hydrolase sequences, responsible for deconjugation reactions in secondary bile acid metabolism. Increased <i>L. reuteri</i> levels were further associated with mevalonate-dependent isopentenyl diphosphate (IPP) biosynthesis and o-succinylbenzoate synthase, a menaquinone biosynthesis associated gene. Analysis of the gut microbiomes from cirrhosis patients identified an increased abundance of genes from the mevalonate-dependent IPP biosynthesis as well as several other menaquinone biosynthesis genes, including o-succinylbenzoate synthase. These results extend the association of lactobacilli with the AhR/intestinal axis in NAFLD progression and highlight the similarities between TCDD-elicited phenotypes in mice to human NAFLD.
format	article
author	Russell R. Fling Timothy R. Zacharewski
author_facet	Russell R. Fling Timothy R. Zacharewski
author_sort	Russell R. Fling
title	Aryl Hydrocarbon Receptor (AhR) Activation by 2,3,7,8-Tetrachlorodibenzo-<i>p</i>-Dioxin (TCDD) Dose-Dependently Shifts the Gut Microbiome Consistent with the Progression of Non-Alcoholic Fatty Liver Disease
title_short	Aryl Hydrocarbon Receptor (AhR) Activation by 2,3,7,8-Tetrachlorodibenzo-<i>p</i>-Dioxin (TCDD) Dose-Dependently Shifts the Gut Microbiome Consistent with the Progression of Non-Alcoholic Fatty Liver Disease
title_full	Aryl Hydrocarbon Receptor (AhR) Activation by 2,3,7,8-Tetrachlorodibenzo-<i>p</i>-Dioxin (TCDD) Dose-Dependently Shifts the Gut Microbiome Consistent with the Progression of Non-Alcoholic Fatty Liver Disease
title_fullStr	Aryl Hydrocarbon Receptor (AhR) Activation by 2,3,7,8-Tetrachlorodibenzo-<i>p</i>-Dioxin (TCDD) Dose-Dependently Shifts the Gut Microbiome Consistent with the Progression of Non-Alcoholic Fatty Liver Disease
title_full_unstemmed	Aryl Hydrocarbon Receptor (AhR) Activation by 2,3,7,8-Tetrachlorodibenzo-<i>p</i>-Dioxin (TCDD) Dose-Dependently Shifts the Gut Microbiome Consistent with the Progression of Non-Alcoholic Fatty Liver Disease
title_sort	aryl hydrocarbon receptor (ahr) activation by 2,3,7,8-tetrachlorodibenzo-<i>p</i>-dioxin (tcdd) dose-dependently shifts the gut microbiome consistent with the progression of non-alcoholic fatty liver disease
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/41119752f628489ea5a9b3ddd7de6fcb
work_keys_str_mv	AT russellrfling arylhydrocarbonreceptorahractivationby2378tetrachlorodibenzoipidioxintcdddosedependentlyshiftsthegutmicrobiomeconsistentwiththeprogressionofnonalcoholicfattyliverdisease AT timothyrzacharewski arylhydrocarbonreceptorahractivationby2378tetrachlorodibenzoipidioxintcdddosedependentlyshiftsthegutmicrobiomeconsistentwiththeprogressionofnonalcoholicfattyliverdisease
_version_	1718411796758396928

Aryl Hydrocarbon Receptor (AhR) Activation by 2,3,7,8-Tetrachlorodibenzo-<i>p</i>-Dioxin (TCDD) Dose-Dependently Shifts the Gut Microbiome Consistent with the Progression of Non-Alcoholic Fatty Liver Disease

Ejemplares similares