This study aimed to demonstrate Gut3Gel as an in vitro platform to effectively assess the effects of microbiota-modulating compounds

The intestinal microbiota plays a key role in human health, influencing digestion, immunity, and metabolism. While factors such as genetics and medications shape its composition, diet remains a primary driver of microbial modulation. Despite growing interest in using dietary interventions to beneficially alter the intestinal microbiota, assessing their effects in humans is challenging due to individual variability and the complexity of in vivo systems. This study explores Gut3Gel gradient colonic preclinical model as a tool to assess its representativeness on studying the effect of inulin supplementation on the intestinal microbiota of five healthy individuals compared to clinical evaluation studies. Significant inter-individual variability in baseline microbiota composition was observed, which strongly influenced microbiota response to inulin. While inulin supplementation led to a general decrease in alpha diversity, it significantly increased the abundance of health-associated genera such as Bifidobacterium and Lacticaseibacillus, along with enhanced microbial metabolic activity. Despite the intrinsic selectivity of Gut3Gel for beneficial microbes, the model successfully captured inulin's prebiotic effects and inter-individual differences, underscoring its relevance as a physiologically relevant high throughput tool for evaluating microbiota-targeting compounds and supporting personalized nutrition strategies.