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<p>The pandemic-scale progression of type 2 diabetes mellitus (T2DM) necessitates innovative interventions targeting the pathogenic triad of insulin resistance, dysregulation of lipid metabolism, and gut microbiome dysbiosis. Here, we report a synthetically bioengineered probiotic consortium (REcN-F/Ca) developed through directed metabolic adaptations of <i>Escherichia coli</i> Nissle 1917 (EcN) under iterative hydrogen peroxide selection, subsequently functionalized with fructooligosaccharide-calcium carbonate composites. REcN-F/Ca exhibits enhanced reactive oxygen species tolerance through upregulated antioxidant enzymes and hydrogen sulfide-mediated redox balancing, alongside improved gastrointestinal survivability. In high-fat diet-induced obese male mice, REcN-F/Ca restores gut microbiota diversity, enriches butyrogenic taxa (Lachnospiraceae and <i>Blautia</i>), and rescues short-chain fatty acids depletion. Transcriptomic profiling reveals PPAR signaling activation, driving lipid metabolism and suppressing adipose inflammation. These effects translate to systemic metabolic improvements with attenuated weight gain (−25.4%), restored glucose homeostasis, and reduced insulin resistance (HOMA-IR: −73.2%) in the obesity and T2DM murine model. Our findings establish REcN-F/Ca as a synthetically engineered probiotic that simultaneously corrects intestinal ecological perturbations and reverses host metabolic dysfunction, proposing a paradigm for metabolic syndrome management.</p>

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Bioengineered ROS-tolerant probiotic reshapes gut microbiota-host axis to ameliorate type 2 diabetes in male mice

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月2日

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  • Congyang Mao,
  • Wanyu Jin,
  • Limeng Dou,
  • Tong Guo,
  • Jin Huang,
  • Yi Wang,
  • Xiangmei Liu,
  • Shuilin Wu,
  • Wei Qiao,
  • Yiming Xiang,
  • Yizhou Zhu,
  • Jun Wu,
  • Kelvin Wai Kwok Yeung

摘要

The pandemic-scale progression of type 2 diabetes mellitus (T2DM) necessitates innovative interventions targeting the pathogenic triad of insulin resistance, dysregulation of lipid metabolism, and gut microbiome dysbiosis. Here, we report a synthetically bioengineered probiotic consortium (REcN-F/Ca) developed through directed metabolic adaptations of Escherichia coli Nissle 1917 (EcN) under iterative hydrogen peroxide selection, subsequently functionalized with fructooligosaccharide-calcium carbonate composites. REcN-F/Ca exhibits enhanced reactive oxygen species tolerance through upregulated antioxidant enzymes and hydrogen sulfide-mediated redox balancing, alongside improved gastrointestinal survivability. In high-fat diet-induced obese male mice, REcN-F/Ca restores gut microbiota diversity, enriches butyrogenic taxa (Lachnospiraceae and Blautia), and rescues short-chain fatty acids depletion. Transcriptomic profiling reveals PPAR signaling activation, driving lipid metabolism and suppressing adipose inflammation. These effects translate to systemic metabolic improvements with attenuated weight gain (−25.4%), restored glucose homeostasis, and reduced insulin resistance (HOMA-IR: −73.2%) in the obesity and T2DM murine model. Our findings establish REcN-F/Ca as a synthetically engineered probiotic that simultaneously corrects intestinal ecological perturbations and reverses host metabolic dysfunction, proposing a paradigm for metabolic syndrome management.