| Popis: |
Background Exposure to persistent organic pollutants (POPs) and gastrointestinal microbial disruption positively corelate with a predisposition to factors including obesity, metabolic syndrome, and type 2 diabetes; however, it is unclear if and how the microbiome contributes to this relationship. Results Here, we show that early-life exposure to a potent aryl hydrocarbon receptor (AHR) agonist in mice resulted in persistent microbiota disruptions associated with impaired glucose homeostasis later in life. 2,3,7,8-tetrachlorodibenzofuran (TCDF)-exposed mice exhibited a profound disruption in the gut microbiome characterized by decreased abundances of Akkermansia muciniphila (A. muciniphila), decreased levels of cecal short chain fatty acids (SCFAs) and indole-3-lactic acid (ILA), and reduction of gut hormones GLP-1 and PYY. Importantly, microbial and metabolic phenotypes associated with early-life POP exposure were transferable to germ-free recipients in the absence of POP carry-over. Consistent with these in vivo studies, we reveal a direct, AHR-independent, POP-microbiota interaction that significantly affected the growth, physiology, gene expression, and metabolic activity of A. muciniphila, resulting in suppressed activity along the ILA pathway. Conclusions These data point to a complex effect 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 which persists into later life with associated health implications. |
