Bioengineered human gut-on-a-chip for advancing non-clinical pharmaco-toxicology

ABSTRACT

Introduction

There is a growing need for alternative models to advance current non-clinical experimental models because they often fail to accurately predict drug responses in clinical trials. Human organ-on-a-chip models have emerged as promising approaches for advancing the predictability of drug behaviors and responses.

Areas covered

We summarize up-to-date human gut-on-a-chip models designed to demonstrate intricate interactions involving the host, microbiome, and pharmaceutical compounds since these models have been reported a decade ago. Our overview covers recent advances in gut-on-a-chip models as a bridge technology between non-clinical and clinical assessments of drug toxicity and metabolism. We highlight the promising potential of the gut-on-a-chip platforms, offering a reliable and valid framework for investigating the reciprocal crosstalk between the host, gut microbiome, and drugs.

Expert opinion

Gut-on-a-chip platforms can attract multiple end users as a predictive, human-relevant, and non-clinical model. Notably, the gut-on-a-chip platforms provide a unique opportunity to recreate a human intestinal microenvironment, including dynamic bowel movement, luminal flow, oxygen gradient, host-microbiome interactions, and disease-specific manipulations restricted in current animal and in vitro cell culture models. Additionally, given the profound impact of the gut microbiome on pharmacological bioprocess, it is critical to leverage the breakthroughs of the gut-on-a-chip technology to address knowledge gaps and drive innovation in predictive drug toxicology and metabolism.

Disclaimer

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Article highlights

• Human gut-on-a-chip models can provide a unique opportunity to recreate an intestinal lumen-capillary transmural interface inhabited by live gut bacteria or microbiota.

• The gut-on-a-chip models allow longitudinal drug-host-microbiome crosstalk under physiological motions and flow.

• The gut-on-a-chip models can provide a reliable platform for interrogating longitudinal drug-host-microbiome interactions.

• Integrating gut-on-a-chip and human organoid technologies may offer a new avenue to build implementable and human-predictive gastrointestinal models to validate the pharmacological outcome of new drug candidates for non-clinical validations.

• The gut-on-a-chip technology may provide a promising value to bridge between non-clinical tests and clinical trials for predictive drug toxicology and metabolism.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

Figures 2 and 3 were created with BioRender.com.

Additional information

Funding

This work was supported in part by the Basic Science Research Program through the National Research Foundation of Korea, funded by the Ministry of Education (2021R1A6A3A14045370 to YC Shin), the Danone North America Gut Microbiome, Yogurt and Probiotics Fellowship Grant (Danone2306NT to N Than), the Crohn’s and Colitis Foundation of America (to HJ Kim), and the Bio-industrial Technology Development Program from the Ministry of Trade, Industry & Energy (MOTIE, Korea; 20018770 to HJ Kim).