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<p>Methylglyoxal (MGO), a reactive dicarbonyl formed during the food processing, induces oxidative stress, inflammation and apoptosis. However, there are little effective methods to reduce MGO-induced cytotoxicity. Here, we screened 35 lactic acid bacteria and identified <i>Lactobacillus fermentum</i> 2-14 as the most effective strain in restoring Caco-2 cell viability and reducing LDH cytotoxicity under MGO challenge. Mechanistically, <i>L. fermentum</i> 2-14 attenuated MGO-induced ROS accumulation, apoptosis and inflammatory responses, and promoted autophagy, as indicated by increased LC3 puncta and autolysosome formation using an RFP–GFP–LC3 reporter. Using integrative transcriptomics and metabolomics, we further suggested that <i>L. fermentum</i> 2-14 activates the AMPK pathway by increasing the level of pyruvate in Caco-2 cells. Supplementing with pyruvate partially mimicked the protective effect in an AMPK- and autophagy-dependent manner. Collectively, our findings indicate that <i>L. fermentum</i> 2-14 mitigates MGO cytotoxicity via a pyruvate–AMPK–autophagy axis, supporting the development of probiotic-based strategies to counter food-derived dicarbonyl stress.</p>

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Lactobacillus fermentum 2-14 mitigates the cytotoxicity induced by methylglyoxal by activating the AMPK-autophagy signaling axis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月20日

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  • Junjun Gao,
  • Yuqin Chen,
  • Junfeng Xiao,
  • Siyu Guo,
  • Manli Li,
  • Yapeng Guo,
  • Lei Wang,
  • Mingye Peng,
  • Yang Chen,
  • Mengzhou Zhou

摘要

Methylglyoxal (MGO), a reactive dicarbonyl formed during the food processing, induces oxidative stress, inflammation and apoptosis. However, there are little effective methods to reduce MGO-induced cytotoxicity. Here, we screened 35 lactic acid bacteria and identified Lactobacillus fermentum 2-14 as the most effective strain in restoring Caco-2 cell viability and reducing LDH cytotoxicity under MGO challenge. Mechanistically, L. fermentum 2-14 attenuated MGO-induced ROS accumulation, apoptosis and inflammatory responses, and promoted autophagy, as indicated by increased LC3 puncta and autolysosome formation using an RFP–GFP–LC3 reporter. Using integrative transcriptomics and metabolomics, we further suggested that L. fermentum 2-14 activates the AMPK pathway by increasing the level of pyruvate in Caco-2 cells. Supplementing with pyruvate partially mimicked the protective effect in an AMPK- and autophagy-dependent manner. Collectively, our findings indicate that L. fermentum 2-14 mitigates MGO cytotoxicity via a pyruvate–AMPK–autophagy axis, supporting the development of probiotic-based strategies to counter food-derived dicarbonyl stress.