Adopting Best Diet–Gut Microbiome Research Practices to Advance Health

Trillions of microbes in the gut support our immune systems and have even been shown to regulate brain function and behavior. Our diet impacts the function, makeup and activity of those gut microbes. Therefore, connecting the two through science is critical to improve our understanding of disease and prevent illness. But what is the best way to investigate these connections through human gut microbiome and nutrition research? A multi-institutional study led by the University of California, Davis and recently published in Advances in Nutrition examines where things stand.

Need for research guidance in diet–gut microbiome studies

Identifying and adopting best practices in diet–microbiome research studies would help scientists studying the gut find answers as to how microbes improve health. In this rapidly evolving field, individual researchers have provided recommendations for elements of research design based on their experience, but currently there are no clear general best practice guidelines. In part, this is because the field evolved rapidly. To understand where we know quite a bit and where uncertainties remain, a first step was to collate and organize human diet–gut microbiome research practices from the public domain. The lack of validated dietary intake biomarkers and the challenge of defining what a “healthy” gut microbiome is, currently constrain the field.

Consensus and knowledge gaps identified, but context is key

Reviewing the last 10 years of publications, I and the other authors identified those that outlined research practice recommendations. These ranged from measuring how closely research subjects adhere to provided diets to linking diet and gut microbiome data to statistical approaches. Common challenges included sample collection, processing, sequencing protocols and the best statistics to use.

The key findings of the paper were:

• Several points of agreement were identified, indicating evolving consensus in this field of research. In the category of study design, these included washout periods greater than four weeks, consideration to clinical and biological significance of findings, specific inclusion and exclusion criteria and baseline consumption of pro- and prebiotics as examples. Points of agreement were also identified in the areas of diet intervention and assessment, biological sample analysis and analyzing, integrating and reporting diet and gut microbiome data.
• The best practice depends upon the research question at hand, as well as the feasibility of implementation.
• Gaps in knowledge included limited data on food composition, understanding how long a new diet needs to be consumed to create lasting effects, incomplete links between the dietary intervention and impacts to health, and the need for statistical approaches that will clarify diet-gut microbiome relationships.

Linking diet and gut microbiome through science catalyzes health insights

While there is some consensus emerging on best practices in diet–gut microbiome studies, our study identified a number of important recurring knowledge gaps. We suggest that addressing these will help facilitate broadly applicable best practices to be established for randomized controlled trials focused on diet–gut microbiome interactions in human health that are ultimately needed to improve reproducibility and advance the field. To the extent possible, study data – especially sequencing and dietary intake data – should be made publicly available to facilitate reanalysis and high-quality meta-analysis as more evidence for various interventions and endpoints becomes available and as databases and methods continue to improve. The review notes that specific decisions across all of the examined categories ultimately depends upon what the study is intended to address, or the “research question.” For this reason best practices are necessarily flexible and adaptable.

Study designs based on research questions and aims that are adequately powered with physiologically meaningful endpoints will carry weight. As gut microbiome-modulating dietary factors are carefully considered in developing interventions and controls, more health insights will result. This review puts a stake in the ground demarking the progress that has been made and opportunities to align study designs going forward. This alignment is fundamental to cross-study comparison and building a body of literature that can be leveraged to develop broader nutrition recommendations.

It should be noted that this study did not include best practices for gut microbiome research outside of those involving nutrition. In addition, only one database was searched (although those reference lists were also examined), and the subjects were limited to free-living adults.

Promoting dialogue on best research practices to advance the field

Though future research and expert discussions are needed to address knowledge gaps and establish and evolve the best practices in the field, significant efforts are already underway. As those efforts continue, the best practices and considerations identified in this review, the publications from which information was extracted and other relevant publications cited throughout, can provide a guide for designing and conducting diet-gut microbiome studies that truly advance the field.

Reference: Diacova T, Cifelli CJ, Davis CD, et al. Best practices and considerations for conducting research on diet–gut microbiome interactions and their impact on health in adult populations: An umbrella review. Adv Nutr. 2025;16(5):100419. doi:10.1016/j.advnut.2025.100419

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