AhR Activation by a Dioxin-like Pollutant Dysregulates Gut-liver Axis

Industrial activities along the Yangtze River (Credit: CHEN Lianguo / IHB)

The activation of aryl hydrocarbon receptor (AhR) by a model dioxin-like pollutant (PCB126) is found to systematically disturb the microbial and metabolic communication across the gut-liver axis. This study, led by Dr. CHEN Lianguo from the Institute of Hydrobiology (IHB) of the Chinese Academy of Sciences, was published in Environmental Science & Technology. 

Mounting evidences confirm the pivotal role of gut microbiota in the maintenance of host health and wellbeing. Dysbiosis of gut microbial community has a high propensity to ultimately develop a set of metabolic syndromes, including systemic inflammation, obesity, and diabetes.    

However, gut microbiota is extremely susceptible to the impacts of environmental pollutants, which can remarkably disrupt the microbial composition, diversity and metabolisms along the gut-liver axis. Previous studies provide preliminary clues about the involvement of AhR pathway in the modulation of gut microbiota, while the underlying mechanisms remain largely unclear.   

To this end, the researchers exposed adult zebrafish (Danio rerio) to PCB126, a model agonist of AhR pathway, with objectives to elucidate the details of how AhR signaling acts to dysregulate the metabolic communication between microbes and the gut, blood, and liver systems with the assistance of metagenomic and metabolomic profiling.   

The results showed that activation of AhR action suppressed the bacterial activities associated with primary bile acid metabolism in the gut, subsequently blocking the conversion and causing the accumulation of primary bile acids therein.   

In addition, PCB126 acute exposure impaired the metabolism of various essential vitamins (e.g., retinol, vitamin B6, and folate). Particularly, bacteria-catalyzed degradation of vitamin B6 was inhibited in male intestines, leading to its intestinal accumulation. It is notable that PCB126 caused systematic deficiency of essential vitamins in female fish.   

Overall, this study finds that AhR signaling activation by PCB126 interrupted the gut microbial activities, underlying the metabolic disorders of bile acids and vitamins along the gut-liver axis.