PMID- 34453844 OWN - NLM STAT- MEDLINE DCOM- 20220323 LR - 20230127 IS - 1096-0929 (Electronic) IS - 1096-6080 (Print) IS - 1096-0929 (Linking) VI - 184 IP - 1 DP - 2021 Oct 27 TI - Neonatal Exposure to BPA, BDE-99, and PCB Produces Persistent Changes in Hepatic Transcriptome Associated With Gut Dysbiosis in Adult Mouse Livers. PG - 83-103 LID - 10.1093/toxsci/kfab104 [doi] AB - Recent evidence suggests that complex diseases can result from early life exposure to environmental toxicants. Polybrominated diphenyl ethers (PBDEs), and polychlorinated biphenyls (PCBs) are persistent organic pollutants (POPs) and remain a continuing risk to human health despite being banned from production. Developmental BPA exposure mediated-adult onset of liver cancer via epigenetic reprogramming mechanisms has been identified. Here, we investigated whether the gut microbiome and liver can be persistently reprogrammed following neonatal exposure to POPs, and the associations between microbial biomarkers and disease-prone changes in the hepatic transcriptome in adulthood, compared with BPA. C57BL/6 male and female mouse pups were orally administered vehicle, BPA, BDE-99 (a breast milk-enriched PBDE congener), or the Fox River PCB mixture (PCBs), once daily for three consecutive days (postnatal days [PND] 2-4). Tissues were collected at PND5 and PND60. Among the three chemicals investigated, early life exposure to BDE-99 produced the most prominent developmental reprogramming of the gut-liver axis, including hepatic inflammatory and cancer-prone signatures. In adulthood, neonatal BDE-99 exposure resulted in a persistent increase in Akkermansia muciniphila throughout the intestine, accompanied by increased hepatic levels of acetate and succinate, the known products of A. muciniphila. In males, this was positively associated with permissive epigenetic marks H3K4me1 and H3K27, which were enriched in loci near liver cancer-related genes that were dysregulated following neonatal exposure to BDE-99. Our findings provide novel insights that early life exposure to POPs can have a life-long impact on disease risk, which may partly be regulated by the gut microbiome. CI - (c) The Author(s) 2021. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Lim, Joe Jongpyo AU - Lim JJ AD - Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington, USA. FAU - Dutta, Moumita AU - Dutta M AD - Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington, USA. FAU - Dempsey, Joseph L AU - Dempsey JL AD - Division of Gastroenterology, Department of Medicine, School of Medicine, University of Washington, Seattle, Washington, USA. AD - Center for Microbiome Sciences and Therapeutics, School of Medicine, University of Washington, Seattle, Washington, USA. FAU - Lehmler, Hans-Joachim AU - Lehmler HJ AUID- ORCID: 0000-0001-9163-927X AD - Department of Occupational and Environmental Health, University of Iowa, Iowa City, Iowa, USA. FAU - MacDonald, James AU - MacDonald J AD - Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington, USA. FAU - Bammler, Theo AU - Bammler T AD - Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington, USA. FAU - Walker, Cheryl AU - Walker C AD - Center for Precision Environmental Health, Baylor College of Medicine, Houston, Texas 77030, USA. AD - Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA. AD - Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA. AD - Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA. AD - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA. FAU - Kavanagh, Terrance J AU - Kavanagh TJ AD - Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington, USA. FAU - Gu, Haiwei AU - Gu H AD - Arizona Metabolomics Laboratory, College of Health Solutions, Arizona State University, Pheonix, Arizona 85004, USA. FAU - Mani, Sridhar AU - Mani S AD - Department of Medicine, Molecular Pharmacology and Genetics, Albert Einstein College of Medicine, Bronx, New York 10461, USA. FAU - Cui, Julia Yue AU - Cui JY AD - Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington, USA. LA - eng GR - P30 ES005605/ES/NIEHS NIH HHS/United States GR - P50 HD103524/HD/NICHD NIH HHS/United States GR - R01 ES031098/ES/NIEHS NIH HHS/United States GR - R01 ES030197/ES/NIEHS NIH HHS/United States GR - T32 ES007032/ES/NIEHS NIH HHS/United States GR - R01 GM111381/GM/NIGMS NIH HHS/United States GR - R01 ES025708/ES/NIEHS NIH HHS/United States GR - P30 ES030285/ES/NIEHS NIH HHS/United States GR - P30 ES007033/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Toxicol Sci JT - Toxicological sciences : an official journal of the Society of Toxicology JID - 9805461 RN - 0 (2,2',4,4',5-brominated diphenyl ether) RN - 0 (Environmental Pollutants) RN - 0 (Halogenated Diphenyl Ethers) RN - DFC2HB4I0K (Polychlorinated Biphenyls) SB - IM MH - Adult MH - Animals MH - Dysbiosis/chemically induced MH - *Environmental Pollutants MH - Female MH - Halogenated Diphenyl Ethers/toxicity MH - Humans MH - Liver MH - Male MH - Mice MH - Mice, Inbred C57BL MH - *Polychlorinated Biphenyls/toxicity MH - Transcriptome PMC - PMC8557404 OTO - NOTNLM OT - adverse health outcomes OT - bioinformatics OT - environmental chemicals OT - epigenetic OT - microbiome OT - toxicogenomics EDAT- 2021/08/29 06:00 MHDA- 2022/03/24 06:00 PMCR- 2022/08/28 CRDT- 2021/08/28 17:04 PHST- 2021/08/29 06:00 [pubmed] PHST- 2022/03/24 06:00 [medline] PHST- 2021/08/28 17:04 [entrez] PHST- 2022/08/28 00:00 [pmc-release] AID - 6359198 [pii] AID - kfab104 [pii] AID - 10.1093/toxsci/kfab104 [doi] PST - ppublish SO - Toxicol Sci. 2021 Oct 27;184(1):83-103. doi: 10.1093/toxsci/kfab104.