1995: Establishing the connection to gut health.
While dietary oligosaccharides have a long history of use for health promotion, particularly in Asia, it was not until 1995 that Glenn Gibson and Marcel Roberfroid expanded the definition of the prebiotic concept with: “nondigestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of bacterial species already resident in the colon, and thus attempt to improve host health”.
The criteria for classifying a substance as a prebiotic were largely constrained by the microbiological tools available at the time. A substance had to:
- Resist hydrolysis and absorption in the upper gastrointestinal tract.
- Act as a selective substrate for a limited number of in the colon.
- Alter the colonic flora toward a healthier composition.
- Induce luminal or systemic effects beneficial to host health.
Consequently, research initially focused heavily on fructooligosaccharides (FOS). These compounds were recognized as prebiotics after demonstrating a selective ability to stimulate the growth of bifidobacteria, a genus generally reputed as beneficial alongside lactobacilli, in human fecal cultures.
Redefining the prebiotic concept for a modern era
Over the last three decades, the definition has undergone critical revisions to accommodate the genomic revolution and our deepening understanding of the microbiome. A pivotal shift occurred with the , which updated the definition to: “a substrate that is selectively utilized by host microorganisms conferring a health benefit”. A definition that was recently reaffirmed by the 2025 expert recommendation.
The challenge for experts was to create a definition that covered a broader scope while retaining the essential characteristics needed to build consensus and align stakeholders. The 2017 and 2025 updates introduced critical expansions to the scope of prebiotics in:
The concept has evolved from a narrow focus on bifidobacteria and lactobacilli to a broader ecological perspective. A prebiotic effect is now considered selective if the modulation of the microbiome (whether compositional, functional, or ecological) can be scientifically linked to a health benefit. Furthermore, the concept now accommodates bacterial cross-feeding: shifts in the microbiome occurring beyond the primary metabolizers can be considered selective modulation.
- Extraintestinal applications
The definition no longer restricts prebiotics to the gut. Anatomical sites such as the skin, oral cavity, and urogenital tract are now recognized targets for prebiotic intervention.
- Non-carbohydrate substrates
By redefining prebiotics as “substrates” the door was opened for non-carbohydrate substances. This includes agents like (poly)phenols and polyunsaturated fatty acids (PUFAs), provided they meet the strict criteria of selective utilization and conferred health benefits.
The 30th-anniversary editorial emphasizes aligning prebiotics with the “One Health” framework, which integrates human, animal, and ecosystem health. As most prebiotics are plant- or fungi-derived, they represent a link between plant physiology (e.g., stress resistance) and sustainable global nutrition.
A central theme in the 2025 literature is the difficulty of establishing causality in human studies specifically, proving that the modulation of the microbiome is the mediator of the observed health benefit. While the definition implies a causal link, rigorous experimental proof in a complex ecosystem is notoriously difficult. Consequently, while establishing causality is strongly advised and should be supported by molecular and statistical tools, strictly proving the mechanism is currently not an absolute requirement for classifying a substance as a prebiotic, provided there is a convincing hypothesis.
2025 Criteria for Classification
To ensure clarity and prevent misuse of the term “prebiotic” in both research and commercial contexts, Hutkins et al. outlined specific minimum criteria for classifying a compound as a prebiotic:
- Substrate: It must be a specific substance utilized by autochthonous microorganisms, not a complete diet.
- Characterization: The substance must be chemically characterized (structure, purity) to ensure reproducibility.
- Selective utilization: Evidence must show modulation of microbiome composition or function.
- Health benefit: A benefit must be demonstrated with a defined dose or serving size in the target host via well-controlled studies, typically randomized controlled clinical trials.
- Concomitant demonstration: Both the health benefit and the microbiome modulation must be measured in the same study.
- Mechanism: A scientifically plausible hypothesis explaining how selective utilization leads to the health benefit is required.
- Safety: The substance must be safe for its intended use in alignment with the corresponding regulatory category.
Despite these guidelines, challenges remain. These include establishing causality within competitive gut niches, navigating varying global regulatory requirements, and overcoming methodological limitations, such as sampling difficulties along the gastrointestinal tract and inter-individual heterogeneity.
Take-home messages
- Stability of the definition: The 2025 expert recommendation confirms the 2017 ISAPP definition: “a substrate that is selectively utilized by host microorganisms conferring a health benefit”.
- Regulatory awareness: Beyond expert consensus, stakeholders must navigate specific country legislation to effectively communicate prebiotic benefits to consumers.
- Future focus: The next decades of research must address inter-individual variability to support personalized nutrition, improve tolerability (e.g., reducing gas production), and rigorously investigate mechanisms to establish causality.
References
- Gibson GR, Roberfroid MB. Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. The Journal of Nutrition. 1995;125(6):1401-1412.
- Gibson, G., Hutkins, R., Sanders, M. et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nature Reviews Gastroenterology & Hepatology. 2017;14(8): 491–502.
- Hutkins R, Walter J, Gibson GR, et al. Classifying compounds as prebiotics — scientific perspectives and recommendations. Nature Reviews Gastroenterology & Hepatology. 2025;22(1):54-70.
- Delzenne NM, Bindels LB. The Prebiotic Concept in Nutrition Celebrates its 30th Anniversary. The Journal of Nutrition. 2025;155(7):2007-2008.
