Microbiota-derived lysophosphatidylcholine alleviates Alzheimer’s disease pathology via suppressing ferroptosis

Alzheimer’s disease (AD) is a pervasive neurodegenerative disorder, and new approaches for its prevention and therapy are critically needed. Here, we elucidate a gut-microbiome-brain axis that offers actionable perspectives for achieving this objective. Using the 5xFAD mouse model, we identify increased Clostridium abundance and decreased Bacteroides abundance as key features associated with β-amyloid (Aβ) burden. Treatment with Bacteroides ovatus , or its associated metabolite lysophosphatidylcholine (LPC), significantly reduces Aβ load and ameliorates cognitive impairment. Mechanistically, LPC acts through the orphan receptor GPR119, inhibiting ACSL4 expression, thereby suppressing ferroptosis and…

• NN
  National Natural Science Foundation of China

  Awards: 82073126, 81874076, 92149304, 32171120, 31871147, 81925011
• CM
  Capital Medical University
• SP
  Special Project for Research and Development in Key areas of Guangdong Province

  Award: 2019B030335001