Hypha Discovery 

What's New - Q3 2026

Investigating the hidden role of the gut in drug metabolism

The human gut is increasingly recognised as an important site of drug metabolism, with both microbial enzymes and chemical reactions in the intestinal environment capable of generating metabolites that can influence drug exposure and individual responses.

At the upcoming DMDG meeting in Prague, Hypha Discovery will present two case studies demonstrating how anaerobic human faecal incubations can uncover gut-derived metabolites that may be difficult to predict using conventional hepatic metabolism studies.

In one study, incubation of ozanimod with human faecal material reproduced reported microbiota-mediated metabolic pathways and revealed an additional previously unreported metabolite. In a second study, work with inavolisib uncovered unusual stercobilin-derived conjugates that had been detected in a human ADME study. Scaling up the faecal incubations enabled these metabolites to be isolated and structurally characterised using NMR spectroscopy.

Together, these studies highlight the value of combining controlled gut microbe incubations with LC-MS/MS, metabolite isolation and NMR to investigate the often-overlooked contribution of the gut to drug metabolism. This approach can provide new insight into unexpected biotransformation pathways and help build a more complete picture of drug disposition during discovery and development, including explaining the origin of some circulating metabolites.