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Early life exposure to environmental contaminants (BDE-47, TBBPA, and BPS) produced persistent alterations in fecal microbiome in adult male miceстатья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus- Авторы: Gomez Matthew V., Dutta Moumita, Suvorov Alexander, Shi Xiaojian, Gu Haiwei, Mani Sridhar, Cui Julia Yue
- Журнал: Toxicological Sciences
- Год издания: 2020
- Издательство: Oxford University Press
- Местоположение издательства: United Kingdom
- DOI: 10.1093/toxsci/kfaa161
- Аннотация: 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 feces of 20-week-old adult male pups (n = 14-23/group). Host gene expression and BA levels were quantified in liver. 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 TBBPA, and Lactobacillus for BPS (LefSe). The community-wide contributions to the shift in microbial pathways were predicted using FishTaco. Consistent with FishTaco predictions, BDE-47 persistently increased fecal and hepatic BAs within the 12α hydroxylation pathway, corresponding to an up-regulation with the hepatic BA-synthetic enzyme Cyp7a1. Fecal BAs were also persistently up-regulated by TBBPA and BPS (LC-MS). TBBPA increased propionic acid and succinate, whereas BPS decreased acetic acid (GC-MS). There was a general trend in the hepatic down-regulation of pro-inflammatory cytokines and the oxidative stress sensor target gene (Nqo1), and a decrease in G6Pdx (the deficiency of which leads to dyslipidemia). In conclusion, maternal exposure to these toxicants persistently modified the gut-liver axis, which may produce an immune-suppressive and dyslipidemia-prone signature later in life.
- Добавил в систему: Суворов Александр Николаевич