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Effects of methylglyoxal on intestine and microbiome composition in aged mice

Emanuela Tirelli1, Mariachiara Pucci1, Margherita Squillario2

  • 1Department of Molecular and Translational Medicine, University of Brescia, Italy.

Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association
|January 25, 2025
PubMed
Abstract

Insights

Dietary methylglyoxal (MGO) disrupts gut health in aged mice by increasing inflammation and altering microbiota. This glycotoxin impacts tight junction proteins and mucus layer thickness, affecting gut barrier function.

Area of Science:

  • Gastroenterology
  • Microbiology
  • Toxicology

Background:

  • Methylglyoxal (MGO) is a reactive compound found in processed foods and is linked to diabetes and neurodegenerative diseases.
  • While MGO's role in systemic diseases is known, its specific effects on the intestine remain under-explored.
  • This study examines the impact of dietary MGO on gut health in aged mice.

Purpose of the Study:

  • To investigate the effects of chronic oral methylglyoxal (MGO) administration on the intestinal health of aged mice.
  • To analyze changes in intestinal inflammation, barrier function, morphology, and microbiota composition following MGO exposure.

Main Methods:

  • Aged mice were administered MGO (100 mg/kg/day) for 4 weeks.
  • Intestinal tissues were analyzed for inflammatory markers, permeability, and tight junction proteins (zonulin-1, occludin) using RT-PCR and immunohistochemistry.
  • 16S rRNA gene sequencing was used to characterize gut microbiota composition and metabolic potential.

Main Results:

  • MGO treatment increased MGO-glycated proteins, induced intestinal inflammation, and disrupted tight junctions (zonulin-1, occludin).
  • Intestinal morphology changes included Paneth cell hyperproliferation and a thicker mucus layer.
  • MGO altered microbiota, decreasing butyrate producers (e.g., Ruminococcaceae) and increasing Akkermansia and Lachnospiraceae.

Conclusions:

  • Dietary methylglyoxal (MGO) negatively impacts intestinal homeostasis in aged mice.
  • MGO exposure affects gut barrier integrity, induces inflammation, and reshapes the gut microbiota.
  • These findings suggest a link between dietary glycotoxins, gut dysbiosis, and compromised gut function.
Keywords:
Advanced glycation end productsAged-miceMethylglyoxalMicrobiota compositionPaneth cellsSmall intestine

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