WHAT IS ALREADY KNOWN ON THIS TOPIC

  • Sodium oligomannate (GV-971) modulates gut microbiota, reduces amyloid pathology and enhances cognition in Alzheimer’s disease (AD) models; however, its clinical responses vary widely. Unravelling the mechanisms underlying this heterogeneity is thus essential for personalised treatment.

    • WHAT THIS STUDY ADDS

  • GV-971 drives reductive gut remodelling, which shifts tryptophan metabolic flux toward indole-3-propionic acid (IPA) production—unveiling a gut-brain axis signal that directly links microbial metabolism to host therapeutic outcomes.

    • HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

  • This study complements the rational design of gut microbiome-targeted drugs and provides a framework for predicting responses to carbohydrate-based AD therapies.

  • Restoring bacterial reductive tryptophan-IPA metabolism offers a promising node for therapeutic intervention in Alzheimer’s disease.

    • Introduction

    Alzheimer’s disease (AD) remains incurable, with clinically meaningful therapeutic benefit being limited and highly variable across patients.1 Beyond amyloid-β (Aβ) and tau pathology, AD involves coordinated disturbances in inflammatory, immune, synaptic…