{"title":"Effects of Methylglyoxal on Intestine and Microbiome Composition in Aged Mice.","authors":"Emanuela Tirelli, Mariachiara Pucci, Margherita Squillario, Gloria Bignotti, Serena Messali, Stefania Zini, Mattia Bugatti, Moris Cadei, Maurizio Memo, Arnaldo Caruso, Simona Fiorentini, Vincenzo Villanacci, Daniela Uberti, Giulia Abate","doi":"10.1016/j.fct.2025.115276","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115276"},"PeriodicalIF":3.9000,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Food and Chemical Toxicology","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.1016/j.fct.2025.115276","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"FOOD SCIENCE & TECHNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
期刊介绍:
Food and Chemical Toxicology (FCT), an internationally renowned journal, that publishes original research articles and reviews on toxic effects, in animals and humans, of natural or synthetic chemicals occurring in the human environment with particular emphasis on food, drugs, and chemicals, including agricultural and industrial safety, and consumer product safety. Areas such as safety evaluation of novel foods and ingredients, biotechnologically-derived products, and nanomaterials are included in the scope of the journal. FCT also encourages submission of papers on inter-relationships between nutrition and toxicology and on in vitro techniques, particularly those fostering the 3 Rs.
The principal aim of the journal is to publish high impact, scholarly work and to serve as a multidisciplinary forum for research in toxicology. Papers submitted will be judged on the basis of scientific originality and contribution to the field, quality and subject matter. Studies should address at least one of the following:
-Adverse physiological/biochemical, or pathological changes induced by specific defined substances
-New techniques for assessing potential toxicity, including molecular biology
-Mechanisms underlying toxic phenomena
-Toxicological examinations of specific chemicals or consumer products, both those showing adverse effects and those demonstrating safety, that meet current standards of scientific acceptability.
Authors must clearly and briefly identify what novel toxic effect (s) or toxic mechanism (s) of the chemical are being reported and what their significance is in the abstract. Furthermore, sufficient doses should be included in order to provide information on NOAEL/LOAEL values.