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  • Expert Recommendation
  • Published:

Classifying compounds as prebiotics — scientific perspectives and recommendations

Nature Reviews Gastroenterology & Hepatology volume 22, pages 54–70 (2025)Cite this article

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An Author Correction to this article was published on 16 October 2024

This article has been updated

Abstract

Microbiomes provide key contributions to health and potentially important therapeutic targets. Conceived nearly 30 years ago, the prebiotic concept posits that targeted modulation of host microbial communities through the provision of selectively utilized growth substrates provides an effective approach to improving health. Although the basic tenets of this concept remain the same, it is timely to address certain challenges pertaining to prebiotics, including establishing that prebiotic-induced microbiota modulation causes the health outcome, determining which members within a complex microbial community directly utilize specific substrates in vivo and when those microbial effects sufficiently satisfy selectivity requirements, and clarification of the scientific principles on which the term ‘prebiotic’ is predicated to inspire proper use. In this Expert Recommendation, we provide a framework for the classification of compounds as prebiotics. We discuss ecological principles by which substrates modulate microbiomes and methodologies useful for characterizing such changes. We then propose statistical approaches that can be used to establish causal links between selective effects on the microbiome and health effects on the host, which can help address existing challenges. We use this information to provide the minimum criteria needed to classify compounds as prebiotics. Furthermore, communications to consumers and regulatory approaches to prebiotics worldwide are discussed.

Key points

  • Definition of prebiotic confirmed as “a substrate that is selectively utilized by host microorganisms conferring a health benefit”.

  • Key criteria for prebiotics: defined structure and composition; selectively utilized by host microbiota as measured by microbiome modulation (composition and/or function); mechanistic hypothesis for how the health benefit might be derived from observed microbiome modulation; health benefit and microbiome modulation concomitantly measured; and safe.

  • At least one study in the target host demonstrating both selective utilization by the microbiome and a health benefit is needed to provide correlative evidence for microbiome-mediated health benefits.

  • Confidence that microbiome modulation is causally related to the health benefit can be increased with robust statistical analysis informed by, for example, model systems (in vitro and animal), machine learning and artificial intelligence.

  • A clear definition that reinforces these key scientific characteristics provides an important foundation for understanding what prebiotics are and, importantly, what they are not.

  • Adherence by all stakeholders to these criteria would benefit the prebiotic field by providing cohesion in prebiotic research, principles to underpin regulatory actions and clarity for consumers.

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Fig. 1: Flowchart of commonly employed steps for developing a prebiotic.

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Acknowledgements

This Expert Recommendation evolved from discussions during the 2022 meeting of the International Scientific Association for Probiotics and Prebiotics (ISAPP) among several authors on the prebiotic consensus statement, industry scientists and other experts. Recognizing the value of clarifying criteria for prebiotics in light of the evolution of relevant science, academic experts agreed to serve as co-authors based on involvement in the ISAPP consensus paper on prebiotics9 (Hutkins, Gibson, Scott and Sanders) or due to their expertise, which allowed the paper to expand beyond the concepts previously published. ISAPP is a non-profit organization with a mission to advance the science of probiotics, prebiotics and related substances. ISAPP activities are determined wholly by an all-academic, volunteer board of directors. ISAPP is funded by member companies. We thank S. Theis, BENEO Institute, BENEO GmbH, Obrigheim, Germany, and E. E. Vaughan, Sensus B.V. (Royal Cosun), Roosendaal, the Netherlands, for helpful insights regarding regulatory positioning for prebiotics in several geographic regions and for critical reading of this manuscript. We thank Y. Desjardins, Université Laval, Canada for helpful suggestions on (poly)phenols and E. Deehan (University of Nebraska) for suggestions on resistant starch. We also thank the ISAPP board of directors for critical reading of this manuscript.

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Authors and Affiliations

  1. University of Nebraska, Lincoln, NE, USA

    Robert Hutkins

  2. University College Cork, Cork, Ireland

    Jens Walter

  3. Food and Nutritional Sciences, University of Reading, Reading, UK

    Glenn R. Gibson & Anisha Wijeyesekera

  4. Teagasc Food Research Centre, Cork, Ireland

    Cassandre Bedu-Ferrari

  5. Rowett Institute, University of Aberdeen, Aberdeen, UK

    Karen Scott

  6. Department of Pediatrics, University of California at Davis, Sacramento, CA, USA

    Daniel J. Tancredi

  7. International Scientific Association for Probiotics and Prebiotics, Centennial, CO, USA

    Mary Ellen Sanders

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  8. Mary Ellen Sanders
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Contributions

All authors contributed equally to substantial discussion of the content and writing, and reviewed and/or edited the manuscript before submission. R.H., J.W., G.R.G., C.B.-F., K.S., D.J.T. and A.W. researched data for the article.

Corresponding author

Correspondence to Mary Ellen Sanders.

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Competing interests

R.H. is a founder and co-owner of Synbiotic Health and has received grants from Mead Johnson Nutrition. J.W. is a founder and co-owner of Synbiotic Health and declares support from AgriFibre, Ingredion, MGP ingredients and ConAgra as relevant to this manuscript. G.R.G. has run various industry-funded research projects on prebiotics, none of which influenced the content of this paper. He is a non-paid adviser to the UK All Party Parliamentary Group on Microbiome. He is a member of a scientific advisory board for Deerland Probiotics & Enzymes. K.S. is a volunteer board member of the International Scientific Association for Probiotics and Prebiotics (ISAPP). She has no conflicts relevant to this manuscript. D.J.T. declares support from Deerland Probiotics & Enzymes (statistical consultant and SAB member), International Flavors and Fragrances (statistical consultant), and Synbiotic Health (statistical consultant). He is a volunteer board member of ISAPP. A.W. is a volunteer board member of ISAPP. She declares no conflicts relevant to this manuscript. M.E.S. serves as consulting scientific adviser and formerly as executive science officer for the ISAPP; she has consulted with Bayer, Pepsico, and the Bill and Melinda Gates Foundation; served on scientific advisory boards for Institute for Advancement of Food and Nutrition Sciences, United States Pharmacopeia, Danone NA, Sanofi and Cargill; and has been compensated for giving talks for Xpeer, Sanofi, European Federation of Association of Dietitians and Associated British Foods. C.B.-F. declares no competing interests.

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Nature Reviews Gastroenterology & Hepatology thanks Laure Bindels, Tatiana Pimentel, Kieran Tuohy and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Hutkins, R., Walter, J., Gibson, G.R. et al. Classifying compounds as prebiotics — scientific perspectives and recommendations. Nat Rev Gastroenterol Hepatol 22, 54–70 (2025). https://doi.org/10.1038/s41575-024-00981-6

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