Drug enteric metabolism in gut microbiota-brain crosstalk

Area of Science:

• Neuroscience
• Microbiology
• Pharmacology

Background:

• Neurodegenerative diseases (NDs), including Alzheimer's (AD) and Parkinson's (PD), are major global health burdens.
• The gut-brain axis and gut microbiota (GMB) are increasingly implicated in ND pathogenesis, with a surge in research.
• Intestinal dysbiosis and gut-derived metabolites are linked to neurodegeneration, but often poorly characterized.

Purpose of the Study:

• To critically review the gut-derived metabolism of drugs affecting the GMB and gut-brain axis.
• To highlight the importance of assessing enteric metabolism in drug development for NDs.
• To examine common therapeutic agents, non-prescription drugs, and supplements for AD and PD.

Main Methods:

• Literature review of scientific publications from the last decade.
• Focus on studies investigating drug metabolism by the GMB.
• Analysis of the impact of gut metabolism on drug efficacy and the gut-brain axis.

Main Results:

• Gut microbiota significantly metabolize drugs, impacting their efficacy and pharmacokinetic properties.
• Enteric metabolism can either hinder or enhance drug activity, affecting CNS outcomes.
• Limited identification of specific gut-derived metabolites and their CNS effects in current research.

Conclusions:

• Assessing enteric metabolism is vital for effective drug design and pharmacokinetic studies for NDs.
• The GMB plays a critical role in modulating the gut-brain axis and neurological health.
• Further research is needed to fully elucidate the mechanisms linking gut metabolism to neurodegeneration.