{"doi":"10.1093/toxsci/kfaa161","title":"Early Life Exposure to Environmental Contaminants (BDE-47, TBBPA, and BPS) Produced Persistent Alterations in Fecal Microbiome in Adult Male Mice","abstract":"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, tetrabromobisphenol [TBBPA], and bisphenol S [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, 10 ml/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 with 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 (liquid chromatography-mass spectrometry). TBBPA increased propionic acid and succinate, whereas BPS decreased acetic acid (gas chromatography-mass spectrometry). There was a general trend in the hepatic down-regulation of proinflammatory 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.","journal":"Toxicological Sciences","year":2020,"id":93483,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":40,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9588,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":385440,"name":"Moumita Dutta","orcid":"0000-0002-4893-4377","position":1,"is_corresponding":false},{"id":466991,"name":"Alexander Suvorov","orcid":"0000-0002-2757-5897","position":2,"is_corresponding":false},{"id":331094,"name":"Xiaojian Shi","orcid":"0000-0001-7456-2901","position":3,"is_corresponding":false},{"id":331095,"name":"Haiwei Gu","orcid":"0000-0002-7598-5022","position":4,"is_corresponding":false},{"id":236183,"name":"Sridhar Mani","orcid":"0000-0003-4132-6157","position":5,"is_corresponding":false},{"id":342633,"name":"Julia Yue Cui","orcid":"0000-0002-8564-1784","position":6,"is_corresponding":false},{"id":468377,"name":"Matthew V Gomez","orcid":null,"position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-18T22:31:34.149524Z","pmid":"33078840","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}