Benzo[a]pyrene induces pyroptotic colon damage and gut dysbacteriosis by activating Aryl Hydrocarbon Receptor

Benzo[a]pyrene (BaP) is a kind of carcinogenic, teratogenic, and immunotoxic injurant in high-temperature processed foods. Aryl hydrocarbon receptor (AHR) is widely expressed in various cell types throughout the body and initiates cell death through beginning with ligand binding. AHR plays a crucial role in BaP metabolism. In this study, AHR antagonist CH223191 was used to investigate the toxic effects of BaP on colon tissues in mice by activating AHR. The study revealed that BaP led to an increase in the mRNA expression of inflammatory cytokines (TNF- α, IL-1 β, IL-6, and IL-10) and pyroptosis markers (NF-κB, NLRP3, Caspase-1, and GSDMD) in mouse colon tissues by activating AHR. Similarly, BaP caused a decrease in the levels of ZO-1, MUC2, and Occludi. Furthermore, CH223191 showed promise in mitigating the pyroptotic damage to the colon induced by BaP. Notably, BaP altered the gut microbiota by activating AHR, resulting in a reduction in the abundance of several beneficial bacteria genera, such as Lactobacillus, Bacteroides, Alistipes, and Rikenella, following BaP exposure. However, CH223191 was able to effectively reverse this adverse change. In summary, BaP damaged the intestinal barrier, caused pyroptotic colon damage in mice, and altered the gut microbiota by binding to and activating AHR.