Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
Center for Genome and Microbiome Research, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
Int J Mol Sci. 2023 Jun 27;24(13):10691. doi: 10.3390/ijms241310691.
Polycyclic aromatic hydrocarbons, e.g., benzo[a]pyrene (BaP), are common dietary pollutants with potential carcinogenic activity, while polyphenols are potential chemopreventive antioxidants. Although several health benefits are attributed to polyphenol-rich pomegranate, little is known about its interaction with BaP. This study integrates histochemical, microbiomic, and metabolomic approaches to investigate the protective effects of pomegranate juice from BaP-induced pathologies. To this end, 48 Sprague-Dawley rats received, for four weeks, either pomegranate, BaP, both, or neither ( = 12 rats per group). Whereas histochemical examination of the colon indicated tissue damage marked by mucin depletion in BaP-fed animals, which was partially restored by administration of pomegranate juice, the fecal microbiome and metabolome retained their resilience, except for key changes related to pomegranate and BaP biotransformation. Meanwhile, dramatic microbiome restructuring and metabolome shift were observed as a consequence of the elapsed time (age factor). Additionally, the analysis allowed a thorough examination of fecal microbiome-metabolome associations, which delineated six microbiome clusters (marked by a differential abundance of and , , and ) and two major metabolome clusters (a sugar- and amino-acids-dominated metabotype vs. a cluster of fatty acids and hydrocarbons), with sugar alcohols maintaining a unique signature. In conclusion, using paired comparisons to minimize inter-individual animal variations allowed the dissection of temporal vs. treatment-derived variations. Microbiome-metabolome association clusters may be further exploited for metabotype prediction and gut-health biomarker discovery.
多环芳烃，例如苯并[a]芘（BaP），是常见的饮食污染物，具有潜在的致癌活性，而多酚则是潜在的化学预防抗氧化剂。尽管富含多酚的石榴具有多种健康益处，但人们对其与 BaP 的相互作用知之甚少。本研究综合应用组织化学、微生物组学和代谢组学方法，研究石榴汁对 BaP 诱导的病理学的保护作用。为此，48 只 Sprague-Dawley 大鼠接受了为期四周的石榴、BaP、两者或两者都没有（每组 12 只大鼠）的处理。虽然对结肠的组织化学检查表明，BaP 喂养的动物存在以粘蛋白耗竭为特征的组织损伤，但石榴汁的给药部分恢复了这种损伤，而粪便微生物组和代谢组保持了其弹性，除了与石榴和 BaP 生物转化相关的关键变化。与此同时，由于时间的流逝（年龄因素），观察到了剧烈的微生物组重构和代谢组转移。此外，该分析允许对粪便微生物组-代谢组关联进行全面检查，该分析划定了六个微生物组簇（以 和 、 、和 的差异丰度为特征）和两个主要的代谢组簇（以糖和氨基酸为主的代谢型与以脂肪酸和碳氢化合物为主的代谢型），糖醇保持着独特的特征。总之，使用配对比较来最小化个体间动物变异，可以区分时间变异与处理衍生的变异。微生物组-代谢组关联簇可以进一步用于代谢型预测和肠道健康生物标志物的发现。
