The way forward: Towards pragmatic preclinical microbiome research in inflammatory bowel disease

Clinical trials for inflammatory bowel disease are primarily randomized clinical trials, which have been the gold standard since the 1940s. However, these trials often focus on a specific group of patients, are expensive, and focus on one treatment option over a short period. Challenges in IBD research include environmental triggers, preclinical mechanisms, novel technologies, precision medicine, and pragmatic clinical research. Pragmatic research aims to generate evidence for real-world clinical practice by including diverse patient populations and assessing outcomes that matter to patients and healthcare providers. Advancements in biomedical research require high-quality translational research and successfully preclinical models able to convert promising laboratory results into clinical applications. Such approaches increase external validity of results, informs decision-making, optimizes care strategies, and improves outcomes for IBD patients. Specifically, increasing both internal and external validity remains a challenge in both in vitro/ex vivo and in vivo preclinical research. Therefore, we here aim to give an overview of recent advances in preclinical research models for IBD both in vitro/ex vivo and in vivo and pragmatic strategies to implement with a specific focus on microbiome research. While each model has its limitations, combining and implementing various techniques can provide a comprehensive preclinical evaluation. Advances in the field, such as personalized gut-on-a-chip models and humanized spontaneous animal models, will facilitate more pragmatic and effective strategies for identifying, evaluating, and predicting responses to potential new therapeutics in future research.