Bacteria-derived glutarate mitigates Alzheimer’s disease model pathology through autophagy-lysosomal pathway
Year: 2026
Type: article
Abstract: 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.
Source: Cell Communication and Signaling
Authors: Cui Deng, Mingqin Qu, Wei Yao, Xiaotong Hu, Yan Li, Weilun Zheng, Yiying Zhai, Fangyan Liu, Ting Yang, Tianlong Wang, Xiangming Wang
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,390
Award: G1249579949
OpenAlex ID: W7165160342