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AuthorKorecka, Agata
AuthorDona, Anthony
AuthorLahiri, Shawon
AuthorTett, Adrian James
AuthorAl-Asmakh, Maha
AuthorBraniste, Viorica
AuthorD'Arienzo, Rossana
AuthorAbbaspour, Afrouz
AuthorReichardt, Nicole
AuthorFujii-Kuriyama, Yoshiaki
AuthorRafter, Joseph
AuthorNarbad, Arjan
AuthorHolmes, Elaine
AuthorNicholson, Jeremy
AuthorArulampalam, Velmurugesan
AuthorPettersson, Sven
Available date2017-12-28T07:00:32Z
Publication Date2016-08-24
Publication Namenpj Biofilms and Microbiomesen_US
Identifierhttp://dx.doi.org/10.1038/npjbiofilms.2016.14
CitationA Korecka et al. "Bidirectional communication between the Aryl hydrocarbon Receptor (AhR) and the microbiome tunes host metabolism".(2016), NPJ Biofilms Microbiomes 2, 16014.pp. 1-10
ISSN2055-5008
URIhttp://hdl.handle.net/10576/6034
AbstractThe ligand-induced transcription factor, aryl hydrocarbon receptor (AhR) is known for its capacity to tune adaptive immunity and xenobiotic metabolism-biological properties subject to regulation by the indigenous microbiome. The objective of this study was to probe the postulated microbiome-AhR crosstalk and whether such an axis could influence metabolic homeostasis of the host. Utilising a systems-biology approach combining in-depth (1)H-NMR-based metabonomics (plasma, liver and skeletal muscle) with microbiome profiling (small intestine, colon and faeces) of AhR knockout (AhR(-/-)) and wild-type (AhR(+/+)) mice, we assessed AhR function in host metabolism. Microbiome metabolites such as short-chain fatty acids were found to regulate AhR and its target genes in liver and intestine. The AhR signalling pathway, in turn, was able to influence microbiome composition in the small intestine as evident from microbiota profiling of the AhR(+/+) and AhR(-/-) mice fed with diet enriched with a specific AhR ligand or diet depleted of any known AhR ligands. The AhR(-/-) mice also displayed increased levels of corticosterol and alanine in serum. In addition, activation of gluconeogenic genes in the AhR(-/-) mice was indicative of on-going metabolic stress. Reduced levels of ketone bodies and reduced expression of genes involved in fatty acid metabolism in the liver further underscored this observation. Interestingly, exposing AhR(-/-) mice to a high-fat diet showed resilience to glucose intolerance. Our data suggest the existence of a bidirectional AhR-microbiome axis, which influences host metabolic pathways.
SponsorThe European Community's Seventh Framework Programme (FP7/2007–2013) under grant agreement no. 222720-2 (TORNADO) and grant agreement no. 215553-2 (CrossTalk), as well as from a grant from Swedish Research Council and Henning and Johan Throne-Holst foundation, Lillian Sagens and Curt Ericssons Foundation, SCELSE microbiome centre and LKC School of Medicine NTU, Singapore.
Languageen
PublisherNature Publishing Group in partnership with Nanyang Technological University
SubjectMicrobiota
SubjectMicrobiome
SubjectAryl hydrocarbon Receptor
TitleBidirectional communication between the Aryl hydrocarbon Receptor (AhR) and the microbiome tunes host metabolism
TypeArticle
Pagination1-10
Issue Number2
dc.identifier.essn 2055-5008
workflow.import.source pubmed


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