Modernizing gut-brain axis research in nutritional Science: The role of human-centered New Approach Methodologies

The gut-brain axis is a complex communication network that connects the gastrointestinal system with the central nervous system, significantly influencing various health outcomes, such as mental health, cognitive function, metabolic regulation, and immune responses. While traditional research models, particularly animal studies, have provided valuable insights, they often overlook the intricate and human-specific interactions within this axis. Consequently, translating findings from these models into clinical applications has been challenging. However, recent advancements in human-based Novel Approach Methodologies (NAMs), like organoids, organs-on-chip, and omic sciences, present innovative tools for investigating the gut-brain axis with improved accuracy and relevance to human physiology. These methodologies facilitate a deeper understanding of the molecular and cellular mechanisms by which nutritional interventions affect not only mental health but also a wider range of gut-brain-related health outcomes. Scope and approach: Scope and approach: This paper explores how NAMs are revolutionizing gut-brain axis research by providing more accurate models that replicate human physiology, thereby replacing less effective traditional approaches. By using these advanced methods, researchers can produce detailed data that better mirror human responses to dietary components, resulting in more effective and personalized strategies for managing and enhancing gut-brain health. Future research should concentrate on utilizing NAMs to deepen our understanding of the gut-brain axis in nutritional science, which will ultimately lead to more targeted and effective health interventions for various conditions. • Traditional models fall short on human-specific diet-gut-brain interactions. • Gut-brain axis research shifts toward human-centered, non-animal models. • Organoids and organ-chips advance understanding of diet-gut-brain interactions. • Omic sciences uncover complex diet-microbiome-neurotransmitter connections. • Integrating NAMs offers a complete view of diet's impact on gut-brain health.