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

IF 2.8 4区 农林科学 Q2 FOOD SCIENCE & TECHNOLOGY Food Biophysics Pub Date : 2024-10-30 DOI:10.1007/s11483-024-09890-2
Yingyu Jia, Yao Meng, Zhulin Wang, Hao Li, Jianke Li, Li Yuan
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Abstract

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.

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苯并[a]芘通过激活芳基烃受体诱发脓毒性结肠损伤和肠道细菌病
苯并[a]芘(BaP)是高温加工食品中的一种致癌、致畸和免疫毒性物质。芳基烃受体(AHR)在全身各类细胞中广泛表达,与配体结合后会导致细胞死亡。AHR 在 BaP 的代谢过程中起着至关重要的作用。本研究利用 AHR 拮抗剂 CH223191 研究了 BaP 通过激活 AHR 对小鼠结肠组织的毒性作用。研究结果表明,BaP 通过激活 AHR 增加了小鼠结肠组织中炎症细胞因子(TNF-α、IL-1β、IL-6 和 IL-10)和嗜热标志物(NF-κB、NLRP3、Caspase-1 和 GSDMD)的 mRNA 表达。此外,BaP 还能降低 ZO-1、MUC2 和 Occludin 的水平。此外,CH223191 在减轻 BaP 对结肠造成的脓毒性损伤方面表现出了潜力。值得注意的是,BaP 通过激活 AHR 改变了肠道微生物群,导致在暴露于 BaP 后乳酸杆菌、乳酸杆菌属、Alistipes 和 Rikenella 等几种有益菌属的数量减少。然而,CH223191 能有效逆转这种不利变化。总之,BaP 损害了小鼠的肠道屏障,诱发了小鼠结肠的热变态损伤,并通过与 AHR 结合和激活 AHR 改变了肠道微生物群。
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来源期刊
Food Biophysics
Food Biophysics 工程技术-食品科技
CiteScore
5.80
自引率
3.30%
发文量
58
审稿时长
1 months
期刊介绍: Biophysical studies of foods and agricultural products involve research at the interface of chemistry, biology, and engineering, as well as the new interdisciplinary areas of materials science and nanotechnology. Such studies include but are certainly not limited to research in the following areas: the structure of food molecules, biopolymers, and biomaterials on the molecular, microscopic, and mesoscopic scales; the molecular basis of structure generation and maintenance in specific foods, feeds, food processing operations, and agricultural products; the mechanisms of microbial growth, death and antimicrobial action; structure/function relationships in food and agricultural biopolymers; novel biophysical techniques (spectroscopic, microscopic, thermal, rheological, etc.) for structural and dynamical characterization of food and agricultural materials and products; the properties of amorphous biomaterials and their influence on chemical reaction rate, microbial growth, or sensory properties; and molecular mechanisms of taste and smell. A hallmark of such research is a dependence on various methods of instrumental analysis that provide information on the molecular level, on various physical and chemical theories used to understand the interrelations among biological molecules, and an attempt to relate macroscopic chemical and physical properties and biological functions to the molecular structure and microscopic organization of the biological material.
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