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

Abstract

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 human 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. This 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 gut-on-a-chip platforms, offering a reliable and valid framework for investigating reciprocal crosstalk between the host, gut microbiome, and drug compounds. Expert opinion Gut-on-a-chip platforms can attract multiple end users as predictive, human-relevant, and non-clinical model. Notably, 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 animal and in vitro cell culture models. Additionally, given the profound impact of the gut microbiome on pharmacological bioprocess, it is critical to leverage breakthroughs of gut-on-a-chip technology to address knowledge gaps and drive innovations in predictive drug toxicology and metabolism.