Tirelli Emanuela, Pucci Mariachiara, Squillario Margherita, Bignotti Gloria, Messali Serena, Zini Stefania, Bugatti Mattia, Cadei Moris, Memo Maurizio, Caruso Arnaldo, Fiorentini Simona, Villanacci Vincenzo, Uberti Daniela, Abate Giulia
Department of Molecular and Translational Medicine, University of Brescia, Italy.
IRCCS Ospedale Policlinico San Martino, LISCOMPlab, Genova, Italy.
Food Chem Toxicol. 2025 Mar;197:115276. doi: 10.1016/j.fct.2025.115276. Epub 2025 Jan 23.
Methylglyoxal (MGO), a highly reactive precursor of advanced glycation end products (AGEs), is endogenously produced and prevalent in various ultra-processed foods. MGO has emerged as a significant precursor implicated in the pathogenesis of type 2 diabetes and neurodegenerative diseases. To date, the effects of dietary MGO on the intestine have been limited explored. Thus, this study investigates the impact of prolonged oral administration of MGOs on gut health in aged mice.
Aged mice received MGO chronically (100 mg/kg/day) for 4 weeks Intestinal samples were analyzed using RT-PCR and immunohistochemistry for proinflammatory cytokines, permeability markers, and tight junction proteins. 16S rRNA gene-based microbiome analysis was also performed to characterize microbiome composition and its metabolic potential.
MGO treatment induced notable alterations at the intestinal level, characterized by an increased formation of MGO-glycated proteins with a concurrent induction of a pro-inflammatory status and reduced expression and delocalization of zonulin-1 and occludin, tight junction proteins. Changes in intestinal morphology were also observed, including hyperproliferation of Paneth cells and an augmented thickness of the intestinal mucus layer, as indicated by immunohistochemical data from MGO-treated mice. Investigation into the microbiota composition revealed that MGO is effective in selectively modifying its composition and metabolic pathways. A decreased abundance of bacterial genera associated with the production of acetic and butyric acids (i.e. Harryflintia, Intestinimonas and Ruminococcaceae genera) and a substantial increase in Lachnospiraceae and Akkermansia genera were found in MGO-treated mice.
These findings highlight how dietary MGO can affect intestinal balance, providing valuable insights into the potential links between glycotoxins, gut microbiota, and overall gut functionality.
甲基乙二醛（MGO）是晚期糖基化终产物（AGEs）的一种高反应性前体，在体内内源性产生，并且在各种超加工食品中普遍存在。MGO已成为2型糖尿病和神经退行性疾病发病机制中的一个重要前体。迄今为止，饮食中MGO对肠道的影响研究有限。因此，本研究调查了长期口服MGO对老年小鼠肠道健康的影响。
老年小鼠长期（100mg/kg/天）接受MGO处理4周。使用RT-PCR和免疫组织化学分析肠道样本中的促炎细胞因子、通透性标志物和紧密连接蛋白。还进行了基于16S rRNA基因的微生物组分析，以表征微生物组组成及其代谢潜力。
MGO处理在肠道水平上引起了显著变化，其特征是MGO糖化蛋白的形成增加，同时诱导促炎状态，紧密连接蛋白zonulin-1和闭合蛋白的表达降低和移位。如MGO处理小鼠的免疫组织化学数据所示，还观察到肠道形态的变化，包括潘氏细胞的过度增殖和肠道黏液层厚度增加。对微生物群组成的调查显示，MGO能有效选择性地改变其组成和代谢途径。在MGO处理的小鼠中，发现与乙酸和丁酸产生相关的细菌属（即Harryflintia、肠单胞菌属和瘤胃球菌科属）丰度降低，而毛螺菌科和阿克曼氏菌属显著增加。
这些发现突出了饮食中MGO如何影响肠道平衡，为糖毒素、肠道微生物群和整体肠道功能之间的潜在联系提供了有价值的见解。
