典型文献
Understanding the physiological functions of the host xenobiotic-sensing nuclear receptors PXR and CAR on the gut microbiome using genetically modified mice
文献摘要：
Pharmacological activation of the xenobiotic-sensing nuclear receptors pregnane X receptor(PXR)and constitutive androstane receptor(CAR)is well-known to increase drug metabolism and reduce inflammation.Little is known regarding their physiological functions on the gut microbiome.In this study,we discovered bivalent hormetic functions of PXR/CAR modulating the richness of the gut micro-biome using genetically engineered mice.The absence of PXR or CAR increased microbial richness,and absence of both receptors synergistically increased microbial richness.PXR and CAR deficiency increased the pro-inflammatory bacteria Helicobacteraceae and Helicobacter.Deficiency in both PXR and CAR increased the relative abundance of Lactobacillus,which has bile salt hydrolase activity,corre-sponding to decreased primary taurine-conjugated bile acids(BAs)in feces,which may lead to higher internal burden of taurine and unconjugated BAs,both of which are linked to inflammation,oxidative stress,and cytotoxicity.The basal effect of PXR/CAR on the gut microbiome was distinct from pharma-cological and toxicological activation of these receptors.Common PXR/CAR-targeted bacteria were identified,the majority of which were suppressed by these receptors.hPXR-TG mice had a distinct mi-crobial profile as compared to wild-type mice.This study is the first to unveil the basal functions of PXR and CAR on the gut microbiome.
文献关键词：
中图分类号：
作者姓名：
Mallory Little;Moumita Dutta;Hao Li;Adam Matson;Xiaojian Shi;Gabby Mascarinas;Bruk Molla;Kris Weigel;Haiwei Gu;Sridhar Mani;Julia Yue Cui
作者机构：
Department of Environmental and Occupational Health Sciences,University of Washington,Seattle,WA 98105,USA;Department of Medicine,Molecular Pharmacology and Genetics,Albert Einstein College of Medicine,Bronx,NY 10461,USA;University of Connecticut,Hartford,CT 06106,USA;Arizona Metabolomics Laboratory,College of Health Solutions,Arizona State University,Phoenix,AZ 85004,USA
文献出处：
引用格式：
[1]Mallory Little;Moumita Dutta;Hao Li;Adam Matson;Xiaojian Shi;Gabby Mascarinas;Bruk Molla;Kris Weigel;Haiwei Gu;Sridhar Mani;Julia Yue Cui-.Understanding the physiological functions of the host xenobiotic-sensing nuclear receptors PXR and CAR on the gut microbiome using genetically modified mice)[J].药学学报（英文版）,2022(02):801-820
A类：
androstane,hormetic,hPXR
B类：
Understanding,physiological,functions,host,xenobiotic,sensing,nuclear,receptors,CAR,gut,microbiome,using,genetically,modified,mice,Pharmacological,activation,pregnane,constitutive,well,known,drug,metabolism,reduce,inflammation,Little,regarding,their,In,this,study,discovered,bivalent,modulating,richness,engineered,absence,increased,microbial,both,synergistically,deficiency,inflammatory,bacteria,Helicobacteraceae,Deficiency,relative,abundance,Lactobacillus,which,has,bile,salt,hydrolase,activity,corre,sponding,decreased,primary,taurine,acids,BAs,feces,may,lead,higher,internal,burden,unconjugated,linked,oxidative,stress,cytotoxicity,basal,effect,was,distinct,from,pharma,toxicological,these,Common,targeted,were,identified,majority,suppressed,by,had,profile,compared,wild,type,This,first,unveil
AB值：
0.460739
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