Better study design for better probiotic science

Prof. Hania Szajewska, MDProf. Hania Szajewska, MD Hours
Prodare image 1
Image from Szajewska et al. 2026, published under CC BY 4.0
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Co-author: Dr. Arthur Ouwehand

Probiotic research is growing rapidly. Every year, hundreds of human studies investigate the role of probiotics in gastrointestinal health, immunity, metabolic health, and many other areas. However, one important challenge remains: studies are often difficult to compare.

Unlike most nutritional interventions, probiotics are live microorganisms. Their effects depend on the strain, dose, viability, formulation, and storage conditions, which are not always reported consistently in scientific studies. As a result, studies that seem similar may not be directly comparable. This makes it more difficult to interpret the findings and understand their generalizability, combine results in systematic reviews, or evaluate evidence for regulatory purposes. 

To address this challenge, ILSI Europe brought together academic researchers and scientists from industry to identify the aspects of probiotic research that are not covered by existing methodological guidance. The result was PRODARE (PRObiotic human study Design And REporting) (1), a consensus framework designed to support better study design, conduct, and reporting in probiotic research. 

Not another reporting guideline

Do we really need another reporting guideline? It is a fair question. Researchers already have well-established frameworks such as CONSORT, SPIRIT, and STROBE to use when designing their studies. PRODARE does not replace these guidelines. Instead, it complements them by focusing on issues that are specific to probiotics.

PRODARE addresses important questions for probiotic studies, including: Was the probiotic strain fully characterized? Was viability maintained throughout the study and at what level? Was the dose verified? Were storage conditions appropriate? Were the outcomes measured in a way that allows comparison with other studies?

These are not just technical details. They all matter because without this information, studies are much harder to compare and interpret.

Why this matters

The main aim of PRODARE is to improve probiotic research and assist those who seeking to use the evidence. Regulators need to evaluate evidence from studies that often differ in probiotic strains, doses, formulations, endpoints, and reporting. More consistent study design and reporting should make this evidence easier to assess. Healthcare professionals also rely on high-quality evidence when making recommendations. While researchers may want to use the results to plan additional studies. Better studies should make the evidence easier to interpret, compare, and apply in practice. Ultimately, they should also lead to clearer and more reliable recommendations on the use of probiotics.

Start with the research question

One of the key messages of PRODARE is simple: start with the research question and then choose the most appropriate study design. To help researchers do this, PRODARE includes a practical decision tree that links different research questions with the most suitable study design.

PRODARE image 2 scaled
Image from Szajewska et al. 2026, published under CC BY 4.0

Randomized controlled trials remain the gold standard for evaluating efficacy, but they are not the answer to every question. Exploratory studies help generate more specific hypotheses. Pilot studies assess whether a larger study is feasible and worthwhile. Real-world studies provide information on how probiotics perform in everyday practice, while cohort studies help understand long-term outcomes.

An important contribution of PRODARE is its clear distinction between exploratory and pilot studies. These terms are often used interchangeably, but as mentioned above, serve different objectives and should not be considered as the same.

Better evidence starts with good planning

Many of the PRODARE recommendations are simple and practical. Researchers should clearly identify the probiotic strain, report the dose and viability, collect information on diet and lifestyle, define washout periods, minimize cross-contamination, use standardized outcome measures whenever possible, and preregister clinical studies.

None of these recommendations are new. However, applying them consistently can improve reproducibility, facilitate comparisons across studies, and strengthen the evidence available to clinicians, regulators, systematic reviewers, and guideline developers.

The message is simple: better evidence starts with good study planning and careful reporting.

A framework for the future

PRODARE is more than a reporting checklist. It provides practical recommendations for the design, conduct, analysis, and reporting of human probiotic studies, with the aim of improving their quality, transparency, reproducibility, and comparability.

At the same time, PRODARE should not be viewed as a validated methodological standard. It is an expert consensus framework that will evolve as experience with its application grows.

As probiotic research continues to evolve, choosing the right study design to answer the research question will remain essential. That is the central message of PRODARE.

Reference:

(1) Szajewska H, Benninga M, Chatonidi G, Costabile A, Lane J, van Loo-Bouwman CA, Mersh C, Morales PS, Walton G, Collado MC, Francavilla R, Fulling C, Holbech Jensen BA, Pascual DP, Ross PR, van den Akker CH, Vandenplas Y, Vidra N, Ouwehand AC. Probiotic Human Study Design and Reporting (PRODARE): Recommendations to Improve Research Practice. Adv Nutr. 2026 Jun 2:100668. doi: 10.1016/j.advnut.2026.100668.

Prof. Hania Szajewska, MD

Prof. Hania Szajewska, MD, PhD, is Professor and Chair of the Department of
Paediatrics at the Medical University of Warsaw. Among her various functions,
she served as the Editor-in-Chief of the Journal of Pediatric Gastroenterology
and Nutrition; a member of the Council, and then as the General Secretary of
the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN); the Secretary of the ESPGHAN Committee on Nutrition. Most recently, she joined the Board of Directors of the International Scientific
Association for Probiotics and Prebiotics (ISAPP). Prof. Szajewska has broad
interests in paediatric nutrition but her research focuses on the effects of early
nutritional interventions on later outcome (especially food allergy); and the gut microbiota modifications such as with various biotics (probiotics, prebiotics, synbiotics, postbiotics). She is or has been actively involved in several European Union-funded research projects. She is an enthusiastic advocate for the practice of evidence-based medicine. She has co-authored over 400 PubMed-indexed publications, which have been cited more than 24,000 times, with an H-index of 83.

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