Early-life exposure to a potent Aryl hydrocarbon receptor ligand results in persistent changes to the microbiota and host glucose homeostasis

Abstract 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.