■暴露于持久性有机污染物(POPs)和胃肠道微生物群的破坏与肥胖等因素的易感性呈正相关,代谢综合征,和2型糖尿病;然而,目前尚不清楚微生物组是如何促成这种关系的。
■这项研究旨在探索生命早期暴露于有效的芳香烃受体(AHR)激动剂与微生物群持续破坏之间的关联。导致生命后期代谢稳态受损。
■这项研究使用宏基因组学,基于核磁共振(NMR)和质谱(MS)的代谢组学,和生化分析来分析肠道微生物组的组成和功能,以及生命早期暴露于常规2,3,7,8-四氯二苯并呋喃(TCDF)的生理和代谢作用,无菌(GF),和Ahr-null小鼠。TCDF对粘蛋白的影响(A.粘蛋白)在体外使用光密度(OD600)进行评估,流式细胞术,转录组学,和基于MS的代谢组学。
■暴露于TCDF的小鼠表现出较低的A.muciniphila丰度,较低水平的盲肠短链脂肪酸(SCFA)和吲哚-3-乳酸(ILA),以及较低水平的肠道激素胰高血糖素样肽1(GLP-1)和肽YY(PYY),发现提示肠道微生物群落结构和功能的破坏。重要的是,在没有POP转移的情况下,与生命早期POP暴露相关的微生物和代谢表型可转移至GF接受者.此外,观察到POPs与微生物群之间的AHR独立相互作用,它们与生长密切相关,生理学,基因表达,和粘虫A的代谢活动结果,支持沿ILA途径的抑制活性。
■在小鼠模型中获得的这些数据指出了POPs对宿主和微生物群的复杂影响,提供强有力的证据表明早期生活,短期,自限性POP暴露会对微生物组产生不利影响,影响持续到以后的生活,并对健康产生影响。https://doi.org/10.1289/EHP13356.
UNASSIGNED: Exposure to persistent organic pollutants (POPs) and disruptions in the gastrointestinal microbiota have been positively correlated with a predisposition to factors such as obesity, metabolic syndrome, and type 2 diabetes; however, it is unclear how the microbiome contributes to this relationship.
UNASSIGNED: This study aimed to explore the association between early life exposure to a potent aryl hydrocarbon receptor (AHR) agonist and persistent disruptions in the microbiota, leading to impaired metabolic homeostasis later in life.
UNASSIGNED: This study used metagenomics, nuclear magnetic resonance (NMR)- and mass spectrometry (MS)-based metabolomics, and biochemical assays to analyze the gut microbiome composition and function, as well as the physiological and metabolic effects of early life exposure to 2,3,7,8-tetrachlorodibenzofuran (TCDF) in conventional, germ-free (GF), and Ahr-null mice. The impact of TCDF on Akkermansia muciniphila (A. muciniphila) in vitro was assessed using optical density (OD 600), flow cytometry, transcriptomics, and MS-based metabolomics.
UNASSIGNED: TCDF-exposed mice exhibited lower abundances of A. muciniphila, lower levels of cecal short-chain fatty acids (SCFAs) and indole-3-lactic acid (ILA), as well as lower levels of the gut hormones glucagon-like peptide 1 (GLP-1) and peptide YY (PYY), findings suggestive of disruption in the gut microbiome community structure and function. Importantly, microbial and metabolic phenotypes associated with early life POP exposure were transferable to GF recipients in the absence of POP carry-over. In addition, AHR-independent interactions between POPs and the microbiota were observed, and they were significantly associated with growth, physiology, gene expression, and metabolic activity outcomes of A. muciniphila, supporting suppressed activity along the ILA pathway.
UNASSIGNED: These data obtained in a mouse model point to the complex effects of POPs on the host and microbiota, providing strong evidence that early life, short-term, and self-limiting POP exposure can adversely impact the microbiome, with effects persisting into later life with associated health implications. https://doi.org/10.1289/EHP13356.