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<p>Probiotics exert neuroprotective effects against Alzheimer’s disease (AD) by modulating gut-brain axis pathways, though disease-modifying therapies remain unavailable. Our study revealed that <i>Escherichia coli</i> (<i>E. coli</i>) strain HB101 ameliorated AD-related phenotypes in <i>Caenorhabditis elegans</i>‌ (<i>C. elegans</i>) models, including learning deficits, neurodegeneration, and paralysis. Mechanistically, HB101 reduced amyloid-β (Aβ) aggregation by enhancing lysosomal activity, autophagy, and mitochondrial/endoplasmic reticulum unfolded protein responses (UPRmt/UPRer). Specifically, HB101 activated UPRmt via <i>atfs-1</i> and <i>sphk-1</i>, and UPRer through <i>pek-1</i>. Metabolomic screening pinpointed glutarate as a bioactive metabolite that mitigates AD-related pathology through lysosomal activation and autophagy promotion.</p> Graphical Abstract <p></p>

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Bacteria-derived glutarate mitigates Alzheimer’s disease model pathology through autophagy-lysosomal pathway

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月19日

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  • Cui Deng,
  • Mingqin Qu,
  • Wei Yao,
  • Xiaotong Hu,
  • Yan Li,
  • Weilun Zheng,
  • Yiying Zhai,
  • Fangyan Liu,
  • Ting Yang,
  • Tianlong Wang,
  • Xiangming Wang

摘要

Probiotics exert neuroprotective effects against Alzheimer’s disease (AD) by modulating gut-brain axis pathways, though disease-modifying therapies remain unavailable. Our study revealed that Escherichia coli (E. coli) strain HB101 ameliorated AD-related phenotypes in Caenorhabditis elegans‌ (C. elegans) models, including learning deficits, neurodegeneration, and paralysis. Mechanistically, HB101 reduced amyloid-β (Aβ) aggregation by enhancing lysosomal activity, autophagy, and mitochondrial/endoplasmic reticulum unfolded protein responses (UPRmt/UPRer). Specifically, HB101 activated UPRmt via atfs-1 and sphk-1, and UPRer through pek-1. Metabolomic screening pinpointed glutarate as a bioactive metabolite that mitigates AD-related pathology through lysosomal activation and autophagy promotion.

Graphical Abstract