Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism

Abstract

The dope on l -dopa metabolism The efficacy of l -dopa treatment for Parkinson's disease is hugely variable between individuals, depending on the composition of their microbiota. l -Dopa is decarboxylated into active dopamine, but if the gut microbiota metabolize l -dopa before it crosses the blood-brain barrier, medication is ineffective. Maini Rekdal et al. found that different species of bacterium are involved in l -dopa metabolism (see the Perspective by O'Neill). Tyrosine decarboxylase (TDC) from Enterococcus faecalis and dopamine dehydroxylase (Dadh) from Eggerthella lenta A2 sequentially metabolized l -dopa into m -tyramine. The microbial l -dopa decarboxylase can be inactivated by ( S )-α-fluoromethyltyrosine (AFMT), which indicates possibilities for developing combinations of Parkinson's drugs to circumvent microbial inactivation. Science , this issue p. eaau6323 ; see also p. 1030