Enterococcus hirae QT4713-derived dopamine ameliorates intestinal inflammation and MPTP-induced Parkinson's disease in mice.

Gut microbiota dysbiosis contributes to Parkinson's disease (PD) pathology by altering dopamine metabolism in the gut-brain axis. Although probiotics and other functional strains have been proposed as microbiome-based interventions, few naturally occurring gut microbes show therapeutic potential for PD. Here, we isolated Enterococcus hirae QT4713 (QT4713) from the hypoxic, low-pressure Qinghai-Tibet Plateau (4713 m altitude). Whole-genome sequencing revealed that QT4713 harbors a tyrosine decarboxylase gene (TyrDc), enabling conversion of L-tyrosine to dopamine in vitro. In mice, QT4713 enhanced antioxidant enzyme activity, reduced inflammatory mediators, reshaped gut microbial composition, and promoted short-chain fatty acid production. Metabolomic analyses indicated activation of L-tyrosine metabolism, with increased L-DOPA and dopamine levels in the colon and feces, accompanied by improved motor performance. In an MPTP-induced PD mouse model, QT4713 alleviated motor and gastrointestinal dysfunction, reduced oxidative and inflammatory damage, and attenuated dopaminergic neuron loss. QT4713 also increased dopamine and tyrosine levels in the striatum. Extending beyond an acute toxin model, QT4713 partially rescued PD-like phenotypes in TMEM175 knockout mice, preserving tyrosine hydroxylase-positive neurons in the substantia nigra. Together, these findings suggest that QT4713 can mitigate gastrointestinal disturbances and other PD-related deficits, consistent with combined effects on catecholamine-related metabolism and gut microbiota remodeling.