Dataset Information

PBDEs Altered Gut Microbiome and Bile Acid Homeostasis in Male C57BL/6 Mice.

ABSTRACT: Polybrominated diphenyl ethers (PBDEs) are persistent environmental contaminants with well characterized toxicities in host organs. Gut microbiome is increasingly recognized as an important regulator of xenobiotic biotransformation; however, little is known about its interactions with PBDEs. Primary bile acids (BAs) are metabolized by the gut microbiome into more lipophilic secondary BAs that may be absorbed and interact with certain host receptors. The goal of this study was to test our hypothesis that PBDEs cause dysbiosis and aberrant regulation of BA homeostasis. Nine-week-old male C57BL/6 conventional (CV) and germ-free (GF) mice were orally gavaged with corn oil (10 mg/kg), BDE-47 (100 ?mol/kg), or BDE-99 (100 ?mol/kg) once daily for 4 days (n = 3-5/group). Gut microbiome was characterized using 16S rRNA sequencing of the large intestinal content in CV mice. Both BDE-47 and BDE-99 profoundly decreased the alpha diversity of gut microbiome and differentially regulated 45 bacterial species. Both PBDE congeners increased Akkermansia muciniphila and Erysipelotrichaceae Allobaculum spp., which have been reported to have anti-inflammatory and antiobesity functions. Targeted metabolomics of 56 BAs was conducted in serum, liver, and small and large intestinal content of CV and GF mice. BDE-99 increased many unconjugated BAs in multiple biocompartments in a gut microbiota-dependent manner. This correlated with an increase in microbial 7?-dehydroxylation enzymes for secondary BA synthesis and increased expression of host intestinal transporters for BA absorption. Targeted proteomics showed that PBDEs downregulated host BA-synthesizing enzymes and transporters in livers of CV but not GF mice. In conclusion, there is a novel interaction between PBDEs and the endogenous BA-signaling through modification of the "gut-liver axis".

SUBMITTER: Li CY

PROVIDER: S-EPMC6053593 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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PBDEs Altered Gut Microbiome and Bile Acid Homeostasis in Male C57BL/6 Mice.

Li Cindy Yanfei CY Dempsey Joseph L JL Wang Dongfang D Lee SooWan S Weigel Kris M KM Fei Qiang Q Bhatt Deepak Kumar DK Prasad Bhagwat B Raftery Daniel D Gu Haiwei H Cui Julia Yue JY

Drug metabolism and disposition: the biological fate of chemicals 20180516 8

Polybrominated diphenyl ethers (PBDEs) are persistent environmental contaminants with well characterized toxicities in host organs. Gut microbiome is increasingly recognized as an important regulator of xenobiotic biotransformation; however, little is known about its interactions with PBDEs. Primary bile acids (BAs) are metabolized by the gut microbiome into more lipophilic secondary BAs that may be absorbed and interact with certain host receptors. The goal of this study was to test our hypothe ...[more]

PMID: 29769268

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Project description:BackgroundThe proliferation and survival of microbial organisms including intestinal microbes are determined by their surrounding environments. Contrary to popular myth, the nutritional and chemical compositions, water contents, O2 contents, temperatures, and pH in the gastrointestinal (GI) tract of a human are very different in a location-specific manner, implying heterogeneity of the microbial composition in a location-specific manner.ResultsWe first investigated the environmental conditions at 6 different locations along the GI tract and feces of ten weeks' old male SPF C57BL/6 mice. As previously known, the pH and water contents of the GI contents at the different locations of the GI tract were very different from each other in a location-specific manner, and none of which were not even similar to those of feces. After confirming the heterogeneous nature of the GI contents in specific locations and feces, we thoroughly analyzed the composition of the microbiome of the GI contents and feces. 16S rDNA-based metagenome sequencing on the GI contents and feces showed the presence of 13 different phyla. The abundance of Firmicutes gradually decreased from the stomach to feces while the abundance of Bacteroidetes gradually increased. The taxonomic α-diversities measured by ACE (Abundance-based Coverage Estimator) richness, Shannon diversity, and Fisher's alpha all indicated that the diversities of gut microbiome at colon and cecum were much higher than that of feces. The diversities of microbiome compositions were lowest in jejunum and ileum while highest in cecum and colon. Interestingly, the diversities of the fecal microbiome were lower than those of the cecum and colon. Beta diversity analyses by NMDS plots, PCA, and unsupervised hierarchical clustering all showed that the microbiome compositions were very diverse in a location-specific manner. Direct comparison of the fecal microbiome with the microbiome of the whole GI tracts by α-and β-diversities showed that the fecal microbiome did not represent the microbiome of the whole GI tract.ConclusionThe fecal microbiome is different from the whole microbiome of the GI tract, contrary to a baseline assumption of contemporary microbiome research work.

Dataset Information

PBDEs Altered Gut Microbiome and Bile Acid Homeostasis in Male C57BL/6 Mice.

Publications

PBDEs Altered Gut Microbiome and Bile Acid Homeostasis in Male C57BL/6 Mice.

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