Microbiome-targeted dietary therapy in health and disease: Challenges, opportunities, and pathways forward.

The gut microbiome has an established role in health and disease, and can be manipulated by diet, positioning microbiome-targeted dietary therapies as potential therapeutics. Mounting evidence supports dietary patterns rich in fermentable fibers and lower in nutrient-poor processed foods; however, there are individual, local, and system-wide complexities to adopting and sustaining dietary change as part of therapeutic dietary strategies. Wider adoption of diet therapy is also limited by critical factors that interfere and influence treatment outcomes, the most significant being inter-individual variability in response to dietary therapy, which remains poorly characterized and understood, hindering advancements in precision nutrition. This review examines the role of the gut microbiome in health and disease and describes barriers and solutions for developing and implementing microbiome-targeted dietary interventions as therapeutic strategies. We organize these barriers into three domains: biological, behavioral, and policy and systems, moving from molecular and individual-level mechanisms to population-level systems, and identify evidence gaps and candidate measurable outcomes to guide future research and dietary guideline development.