Microbiota-derived p-cresol and indole metabolites mediates neurotoxic gut-brain axis dysregulation in ALS

ABSTRACT: Integrated metabolomic profiling demonstrated a marked increase in microbiota-derived metabolites, particularly along aromatic amino acid pathways. Notably, p-cresol metabolites were significantly elevated in both brain and circulation, suggesting enhanced microbial phenylalanine/tyrosine metabolism. Accordantly, microbiota analysis revealed persistent dysbiosis, characterized by enrichment of taxa associated with p-cresol production. The SIM analysis of MNs further validated the ultrastructural abnormalities induced by p-cresol sulfate at organelle level. Herbal intervention exacerbated disease progression by enhancing microbiota-dependent metabolic reprogramming, rather than restoring microbial homeostasis. Notably, these pathway-specific alterations are not reflected in population-scale metabolomics data from the UK Biobank, highlighting a critical limitation of conventional metabolic profiling.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse-phase, Liquid Chromatography MS - positive - reverse-phase

PROVIDER: MTBLS14404 | MetaboLights | 2026-08-21

REPOSITORIES: MetaboLights