Benzo[a]Pyrene Induces Pyroptotic Colon Damage and Gut Dysbacteriosis by Activating Aryl Hydrocarbon Receptor

Benzo[a]pyrene (BaP) is a carcinogenic, teratogenic, and immunotoxic injurant in high-temperature processed foods. The Aryl hydrocarbon receptor (AHR) is widely expressed in various cell types throughout the body and initiates cell death upon ligand binding. AHR plays a crucial role in the metabolism of BaP. In this study, the AHR antagonist CH223191 was utilized to investigate the toxic effects of BaP on colon tissues in mice by activating AHR. The findings revealed that BaP increased the mRNA expression of inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-10) and pyroptosis markers (NF-κB, NLRP3, Caspase-1, and GSDMD) in mouse colon tissues through AHR activating. Additionally, BaP resulted in decreased levels of ZO-1, MUC2, and Occludin. Furthermore, CH223191 demonstrated potential in mitigating the pyroptotic damage to the colon induced by BaP. Notably, BaP altered the gut microbiota by activating AHR, leading to a reduction in the abundance of several beneficial bacterial genera, such as Lactobacillus, Bacteroides, Alistipes, and Rikenella, following BaP exposure. However, CH223191 effectively reversed this adverse change. In summary, BaP compromised the intestinal barrier, induced pyroptotic damage in the colon of mice, and altered the gut microbiota by binding to and activating AHR.