Strategies for modelling the intestinal mucus interface: Focus on drug transport and host-microbiota interactions

The intestinal mucus barrier is a complex, dynamic hydrogel that plays a central role in host–microbiota interactions, nutrient transport, and protection against pathogens. Understanding its physicochemical properties has become essential for developing predictive in vitro and in silico models for drug delivery, microbiome research, and disease modelling. Over the past decade, advances in polymer chemistry, glycoscience, and microfluidics have enabled the development of increasingly sophisticated mucus models that mimic structural, rheological, and biochemical features of native intestinal mucus. This review provides a comprehensive overview of recent progress in gut-mucus chemical model development, focusing on mucin biochemistry, hydrogel-based synthetic systems, microphysiological platforms, and an introduction on computational modelling approaches. Special emphasis is placed on emerging strategies to reproduce mucus heterogeneity, viscoelasticity, and microbial interactions. We critically assess the strengths and limitations of current models and highlight future directions for improving physiological relevance, including multi-scale integration and personalized mucus modelling. This review aims to provide a framework for researchers developing next-generation mucus models for biomedical and pharmaceutical applications.