The human microbiota in drug development
Incorporating the human gut microbiota in development of pharmacological and nutritional products is essential for a simple reason: The human microbiota plays a central role for metabolism of both food and medical products. The diverse organisms constituting the microbiota take part in the breakdown, absorption and excretion of ingested components and are thereby essential for the post-ingestion bioavailability and effect of the components.
The mode of interaction between drugs and the human gut microbiota is diverse and to an extend circular as drugs can affect the microbiota, while the microbiota affects metabolism of ingested drugs.
The microbiota is known to affect drug metabolism in two ways. First by the organisms’ direct catabolism of the drugs or pro-drugs into metabolites with altered activity, clearance rate, and potential toxicity, and secondly by the organisms’ ability to maintain intestinal homeostasis, generate metabolites and influence the expression levels of enzymes and transporters important for drug breakdown and transport. Incorporating the microbiome in studies of new drugs and biomarkers is therefore essential to determine a drug’s pharmacokinetics.
Drugs can influence and damage the gut microbiota thereby affecting how the microbiome metabolize other drugs or by reducing the ability of the microbiome to withstand infection as is exemplified by the association between use of proton pump inhibitors and Clostridium difficile infection (Kwok et al., 2012).