Escherichia coli hns and methylglyoxal link gut microbial metabolism to host neuronal gene regulation in Parkinson's disease

An E. coli hns–methylglyoxal (MG) pathway links gut microbial metabolism to dopaminergic neuron vulnerability in Parkinson's disease. Stool metagenomics showed hns, mainly E. coli-derived, enriched in body-first PD, and plasma MG was higher in body-first than brain-first PD and inversely associated with cardiac MIBG uptake. In C. elegans models, Δhns E. coli protected dopaminergic neurons via rig-5, exogenous MG abolished this protection, and corresponding LSAMP changes appeared in human neuronal cells, post-mortem substantia nigra and colonized mice.