Emulating the gut–liver axis: Dissecting the microbiome's effect on drug metabolism using multiorgan-on-chip models

Abstract

The homeostatic relationship between the gut, its microbiome, and the liver is crucial for the regulation of drug metabolism processes. Gut microbes are known to influence human health and disease by enhancing food metabolism and providing a first line of defense against pathogens. In addition to this, the gut microbiome also plays a key role in the processing of exogenous pharmaceutical compounds. Modeling the highly variable luminal gut environment and understanding how gut microbes can modulate drug availability or induce liver toxicity remains a challenge. However, microfluidics-based technologies such as organ-on-chips could overcome current challenges in drug toxicity assessment assays because these technologies are able to better recapitulate complex human responses. Efforts are being made to create in vitro multiorgan platforms, tailored for an individual patient's microbial background. These platforms could be used as a tool to predict the effect of the gut microbiome on pharmacokinetics in a personalized way.

Highlights

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  The gut microbiome and gut barrier integrity play key roles in drug metabolism.

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  Gut barrier disruption leads to inflammation and modifies drug bioavailability.

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  Developing a stem cell–based gut–liver model would pave the way to personalized drug testing and toxicity assessment.