Modelling Metabolic Disorders with Stem Cell-Derived Gut and Liver Organoids: Insights into Probiotic Therapies

Abstract: Metabolic disorders, such as non-alcoholic fatty liver disease (NAFLD), type 2 diabetes, and obesity, are increasingly linked to disruptions in the gut-liver axis and microbiome. Probiotics have gained attention for modulating metabolic health, but their translation from preclinical to clinical use remains limited. Stem cell-derived liver and gut organoids provide advanced in vitro platforms for studying host-microbe interactions and evaluating probiotic therapies in a physiologically relevant context. This review systematically synthesized studies published between 2014 and 2025, obtained from PubMed, Scopus, and Web of Science, focusing on the generation, biological relevance, and translational applications of liver and gut organoids in probiotic therapy research. Key inclusion criteria were studies demonstrating organoid-based modelling of metabolic diseases, microbiome interactions, and high-throughput screening approaches. Gut and liver organoids successfully replicated key tissue functions and host-microbiota dynamics. Probiotics, such as Lactobacillus rhamnosus and Bifidobacterium breve, have been shown to improve gut barrier function, reduce hepatic lipid accumulation, and modulate inflammatory signalling. Integration with high-throughput screening and microbiome co-culture platforms will enhance their predictive value. Organoid-based models bridge the gap between traditional in vitro systems and human clinical relevance, providing detailed insights into the action of probiotics on metabolic pathways. However, challenges remain in terms of reproducibility, vascular and immune integration, and clinical translatability. Stem cell-derived gut and liver organoids represent promising tools for advancing probioticbased therapies in metabolic diseases. Their continued refinement could have a significant impact on personalized medicine and accelerate therapeutic development.