Gut-targeted drugs provide a new drug modality besides that of oral, systemic molecules, that could tap from the growing knowledge of gut metabolites of bacterial or host origin and their involvement in biological processes and health through their interaction with gut targets (bacterial or host, too). Understanding the properties of gut metabolites can provide hints for the design of gut-targeted drugs. In the present work we analyze a large set of gut metabolites, both shared with serum or present only in gut, and compare them with oral systemic drugs. We find patterns specific for these two subsets of metabolites that could be used to design drugs targeting the gut. In addition, we develop and openly share a Super Learner model to predict gut permanence, in order to aid in the design of molecules with appropriate profiles to remain in the gut, resulting in molecules with putatively reduced secondary effects and distribution issues.
Analysis of Metabolites in Human Gut: Illuminating the Design of Gut-Targeted Drugs
21 August 2023, Version 2
This content is a preprint and has not undergone peer review at the time of posting.