PR001958 (Project)

Description: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. This study utilized metagenomics, NMR- and mass spectrometry-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 mass spectrometry-based metabolomics. TCDF-exposed mice exhibited disruption in the gut microbiome community structure and function, characterized by lower abundances of A. muciniphila, lower levels of cecal short chain fatty acids (SCFAs) and indole-3-lactic acid (ILA), and a reduction in gut hormones GLP-1 and PYY. 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, significantly affected the growth, physiology, gene expression, and metabolic activity of A. muciniphila, resulting in suppressed activity along the ILA pathway.