Early life exposure to environmental contaminants (BDE-47, TBBPA, and BPS) produced persistent gut dysbiosis in adult male mice

The gut microbiome is a pivotal player in toxicological responses. We investigated the effects of maternal exposure to 3 human health-relevant toxicants (BDE-47, TBBPA, and BPS) on the composition and metabolite levels (bile acids [BAs] and short chain fatty acids [SCFAs]) of the gut microbiome in adult pups. CD-1 mouse dams were orally exposed to vehicle (corn oil, 10ml/kg), BDE-47 (0.2 mg/kg), TBBPA (0.2 mg/kg), or BPS (0.2 mg/kg) once daily from gestational day 8 to the end of lactation (postnatal day 21). 16S rRNA sequencing and targeted metabolomics were performed in fecal DNA of 12-week-old adult male pups (n=14-23/group). BPS had the most prominent effect on the beta-diversity of the fecal microbiome compared to TBPPA and BDE-47 (QIIME). Seventy-three taxa were persistently altered by at least 1 chemical, and 12 taxa were commonly regulated by all chemicals (most of which were from the Clostridia class and were decreased). The most distinct microbial biomarkers were S24-7 for BDE-47, Rikenellaceae for TBPPA, and Lactobacillus for BPS (LefSe). The community-wide contributions to the shift in microbial pathways were predicted using FishTaco. Fecal BA output was persistently increased by all chemicals (LC-MS). TBBPA increased propionic acid and succinate, whereas BPS decreased acetic acid (GC-MS. In conclusion, maternal exposure to these toxicants persistently modified fecal microbiome and metabolites later in life, and dysbiosis may contribute to the mechanisms of developmental origins of adult-onset of toxic outcomes.