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Given their diverse health\u2010promoting properties, probiotics have emerged as a potential neuroprotective strategy. Through screening in transgenic\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    (\n                    <jats:italic>C. elegans<\/jats:italic>\n                    ) models of \u03b1\u2010synuclein (\u03b1\u2010syn)\u2010induced PD, we identified the\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    (\n                    <jats:italic>E. coli<\/jats:italic>\n                    ) strain E8 as a candidate that effectively suppressed dendritic degeneration and motor deficits. These neuroprotective improvements were attributed to the reduction of \u03b1\u2010syn aggregation, which was mechanistically associated with E8's ability to promote autophagy. Metabolomic profiling further pinpointed 1\u2010allylpiperazine (1\u2010ALPP) as a bioactive metabolite responsible for rescuing PD\u2010related impairments, which was sufficient to recapitulate the autophagy activation induced by E8. Subsequent mechanistic studies revealed that 1\u2010ALPP activated autophagy through the AMPK\/mTOR\/HLH\u201030 pathway. Notably, 1\u2010ALPP effectively inhibited \u03b1\u2010syn fibrillogenesis and cytotoxicity in a dose\u2010dependent manner, potentially via the inhibition of \u03b1\u2010syn liquid\u2010liquid phase separation (LLPS). Molecular simulations demonstrated that 1\u2010ALPP binds to \u03b1\u2010syn, thereby preventing the critical conformational changes required for fibril formation. Strikingly, the protective effects of E8 against PD phenotypes were intergenerationally inherited, persisting for two generations in an\n                    <jats:italic>hpl\u20102<\/jats:italic>\n                    \u2010dependent manner.\n                  <\/jats:p>","DOI":"10.1002\/advs.78133","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:12:59Z","timestamp":1791519179000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bacteria\u2010Derived 1\u2010Allylpiperazine Alleviates Symptoms of Parkinson's Disease Model by Promoting Autophagy"],"prefix":"10.1002","author":[{"given":"Mingqin","family":"Qu","sequence":"first","affiliation":[{"name":"Department of Cell Biology School of Basic Medical Sciences Laboratory for Clinical Medicine Capital Medical University  Beijing 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education Tianjin Key Laboratory of Industrial Microbiology College of Biotechnology Tianjin University of Science and Technology Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuhao","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education Tianjin Key Laboratory of Industrial Microbiology College of Biotechnology Tianjin University of Science and Technology Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinling","family":"Lv","sequence":"additional","affiliation":[{"name":"Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education Tianjin Key Laboratory of Industrial Microbiology College of Biotechnology Tianjin University of Science and Technology Tianjin China"},{"name":"Department of Neurology Inner Mongolia People's Hospital  Hohhot China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaman","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Cell Biology School of Basic Medical Sciences Laboratory for Clinical Medicine Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyi","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Cell Biology School of Basic Medical Sciences Laboratory for Clinical Medicine Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cell Biology School of Basic Medical Sciences Laboratory for Clinical Medicine Capital Medical University  Beijing 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