Impacts of PBDE-47 exposure before, during and after pregnancy on the maternal gut microbiome and its association with host metabolism

Abstract

Maternal gut microbiota play an important role in the modulation of offspring disease susceptibility and gut microbiota dysbiosis has been proposed as a mechanism through which toxic environmental chemicals exert their adverse impacts on health. The brominated flame retardants polybrominated diphenyl ethers (PBDEs) are developmental toxicants and induce dysbiotic gut microbiota in offspring. Yet, whether and how PBDEs impact the maternal gut microbiota remain unclear. Here, we sought to investigate the effect of 2,2′,4,4′-tetrabromodiphenyl ether (PBDE-47) exposure from preconception through lactation cessation on maternal gut microbiota and its link to host serum metabolic consequences. Female Sprague-Dawley rats were daily exposed to 10 mg/kg PBDE-47 via oral gavage from ten days before conception until offspring were weaned on postnatal day 21, then maternal fecal and blood samples were collected for microbiome and metabolome analyses by using 16S ribosomal RNA gene sequencing and gas chromatography-mass spectrometry, respectively. Maternal exposure to PBDE-47 showed a distinct profile in gut microbiota compared to control dams, as evidenced by increased Actinobacteria phylum and genera Blautia, Gemella and Phascolarctobacterium, and decreased genera AF12 and Oscillospira. Additionally, global metabolomics analysis identified 26 differential serum metabolites to distinguish PBDE-47 from controls, which were mainly involved in amino acid, lipid, carbohydrate and energy metabolism, further confirmed by pathway analysis. Importantly, the differential serum metabolites are closely correlated with the disturbed gut microbiota in response to PBDE-47. Collectively, our results suggest that maternal gut microbial dysbiosis may serve as a potential mechanism underlying PBDE-47-elicited health hazards to mothers or even offspring.

Keywords

• 2,2′,4,4′-tetrabromodiphenyl ether
• Maternal toxicity
• Maternal exposure
• Gut microbiome
• Serum metabolome