Abstract
Utilizing a simulated gastrointestinal medium which approximates physiological conditions within the mammalian GI tract, experiments aimed at isolating and identifying unique microbial metabolites were conducted. These efforts led to the finding that Escherichia coli, a common member of the gut microbiota, is capable of producing significant quantities of salsolinol. Salsolinol is a neuroactive compound which has been investigated as a potential contributor to the development of neurodegenerative diseases such as Parkinson’s disease (PD). However the origin of salsolinol within the body has remained highly contested. We herein report the first demonstration that salsolinol can be made in vitro in response to microbial activity. We detail the isolation and identification of salsolinol produced by E. coli, which is capable of producing salsolinol in the presence of dopamine with production enhanced in the presence of alcohol. That this discovery was found in a medium that approximates gut conditions suggests that microbial salsolinol production could exist in the gut. This discovery lays the ground work for follow up in vivo investigations to explore whether salsolinol production is a mechanism by which the microbiota may influence the host. As salsolinol has been implicated in the pathogenesis of PD, this work may be relevant, for example, to investigators who have suggested that the development of PD may have a gut origin. This report suggests, but does not establish, an alternative microbiota-based mechanism to explain how the gut may play a critical role in the development of PD as well other conditions involving altered neuronal function due to salsolinol-induced neurotoxicity.
Highlights
Emerging evidence has suggested that there is an association between certain diseases and an altered gut-microbiome
Supernatant was passed through a 2 kDa molecular weight cut off filter and analyzed by UHPLCECD
This study provides the first evidence that common and abundant members of the gut microbiota, namely E. coli and several related enterobacteria, have the capacity to produce salsolinol and that production is enhanced in the presence of alcohol (Figure 4)
Summary
Emerging evidence has suggested that there is an association between certain diseases and an altered gut-microbiome. As part of our approach, we utilize a food-based simulated small intestinal medium (sSIM) which simulates the gastrointestinal environment following food consumption This enabled us to report the ability of common bacterial genera present within the gut to produce neurochemicals that otherwise would not be detected in more common laboratory media [LuriaBertani broth (LB) as a prototypical example] which do not accurately reflect the gut in vivo milieu (Villageliu et al, 2018). During these experiments we noted the appearance of a prominent microbial product of unknown identity (Figure 1) when cultures were inoculated with Escherichia coli. We determined that this microbial product was salsolinol
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