title: Expression of the aryl hydrocarbon receptor contributes to the establishment of intestinal microbial community structure in mice.
abstract: Environmental and genetic factors represent key components in the establishment/maintenance of the intestinal microbiota. The aryl hydrocarbon receptor (AHR) is emerging as a pleiotropic factor, modulating pathways beyond its established role as a xenobiotic sensor. The AHR is known to regulate immune surveillance within the intestine through retention of intraepithelial lymphocytes, functional redistribution of Th17/Treg balance. Consequently, environmental/genetic manipulation of AHR activity likely influences host-microbe homeostasis. Utilizing C57BL6/J Ahr-/+and Ahr-/-co-housed littermates followed by 18 days of genotypic segregation, we examined the influence of AHR expression upon intestinal microbe composition/functionality and host physiology. 16S sequencing/quantitative PCR (qPCR) revealed significant changes in phyla abundance, particularly Verrucomicrobia together with segmented filamentous bacteria, and an increase in species diversity in Ahr-/-mice following genotypic segregation. Metagenomics/metabolomics indicate microbial composition is associated with functional shifts in bacterial metabolism. Analysis identified Ahr-/--dependent increases in ileal gene expression, indicating increased inflammatory tone. Transfer of Ahr-/-microbiota to wild-type germ-free mice recapitulated the increase Verrucomicrobia and inflammatory tone, indicating Ahr-/--microbial dependence. These data suggest a role for the AHR in influencing the community structure of the intestinal microbiota.
authors.affiliation: Center for Molecular Toxicology &Carcinogenesis Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA-16802, USA.
authors.forename: Iain A
authors.initials: IA
authors.lastname: Murray
authors.affiliation: Center for Molecular Toxicology &Carcinogenesis Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA-16802, USA.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Nichols
authors.affiliation: Center for Molecular Toxicology &Carcinogenesis Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA-16802, USA.|Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA-16802, USA.
authors.forename: Limin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Center for Molecular Toxicology &Carcinogenesis Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA-16802, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Patterson
authors.affiliation: Center for Molecular Toxicology &Carcinogenesis Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA-16802, USA.
authors.forename: Gary H
authors.initials: GH
authors.lastname: Perdew