From intestinal food to systems biology: the 30th anniversary of the prebiotic concept

1995: Making the connection with gut health.

Although dietary oligosaccharides have long been used for health promotion, especially in Asia, it was not until 1995 that Glenn Gibson and Marcel Roberfroid expanded the definition of the prebiotic concept to include: “non-digestible 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 large intestine, thereby attempting to improve the health of the host.”

The criteria for classifying a substance as a prebiotic were largely limited 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 in the large intestine.
• Change the intestinal flora towards a healthier composition.
• Cause luminal or systemic effects that are beneficial to the health of the host.

Therefore, research initially focused heavily on fructo-oligosaccharides (FOS). These compounds were recognized as prebiotics after demonstrating a selective ability to stimulate the growth of bifidobacteriaa genus widely known to be useful alongside lactobacilliin human fecal cultures.

Redefining the prebiotic concept for a modern era

Over the past thirty years, the definition has undergone critical revisions to accommodate the genomic revolution and our deepening understanding of the microbiome. A crucial shift occurred with the , which updated the definition to: “a substrate that is selectively used by microorganisms in the host and that confers a health benefit.” A definition recently reaffirmed by the Expert advice 2025.

The challenge for experts was to create a definition that covered a broader scope while retaining the essential features 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 meactobacilli towards a broader ecological perspective. A prebiotic effect is now considered selective if the modulation of the microbiome (compositional, functional or ecological) can be scientifically linked to a health benefit. Furthermore, the concept now allows for bacterial cross-feeding: shifts in the microbiome that occur beyond primary metabolizers can be considered selective modulation.

• Extraintestinal applications

The definition no longer limits prebiotics to the intestines. Anatomical sites such as the skin, oral cavity, and urogenital tract are now recognized targets for prebiotic intervention.

• Non-carbohydrate substrates

Redefining prebiotics as ‘substrates’ opened the door to non-carbohydrate substances. This includes substances such as (poly)phenols and polyunsaturated fatty acids (PUFAs), provided they meet strict criteria of selective use and provide health benefits.

The Editorial 30th anniversary emphasizes aligning prebiotics with the One Health framework, which integrates human, animal and ecosystem health. Because most prebiotics come from plants or fungi, 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 in establishing causality specifically in human studies, providing evidence that the modulation of the microbiome is the mediator of the observed health benefit. Although the definition implies a causal relationship, rigorous experimental evidence in a complex ecosystem is notoriously difficult. Although establishing causality is strongly recommended 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 used by native microorganisms, and not a complete diet.
• Characterization: The substance must be chemically characterized (structure, purity) to ensure reproducibility.
• Selective use: Evidence must demonstrate modulation of microbiome composition or function.
• Health Benefit: A benefit must be demonstrated at a defined dose or portion size in the target host through well-controlled studies, typically randomized controlled clinical trials.
• Simultaneous demonstration: Both health benefit and microbiome modulation should be measured in the same study.
• Mechanism: A scientifically plausible hypothesis is needed that explains how selective use leads to health benefits.
• Safety: The substance must be safe for its intended use in accordance with the corresponding legal category.

Despite these guidelines, challenges remain. These include establishing causality within competing intestinal niches, navigating various global regulatory requirements, and overcoming methodological limitations such as sampling issues along the gastrointestinal tract and inter-individual heterogeneity.

Groceries for home

• Stability of the definition: The 2025 expert recommendation confirms the 2017 ISAPP definition: “a substrate that is selectively used by microorganisms in the host and that provides a health benefit.”
• Regulatory Awareness: In addition to expert consensus, stakeholders must navigate specific national legislation to effectively communicate prebiotic benefits to consumers.
• Future focus: The coming decades of research should address inter-individual variability to support personalized nutrition, improve tolerability (e.g. by reducing gas production), and rigorously investigate mechanisms to establish causality.

References

1. Gibson GR, Roberfroid MB. Dietary modulation of the human gut microbiota: introducing the concept of prebiotics. The magazine for nutrition. 1995;125(6):1401-1412.
2. 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 and Hepatology. 2017;14(8):491–502.
3. Hutkins R, Walter J, Gibson GRet al. Classifying compounds as prebiotics: scientific perspectives and recommendations. Nature Reviews Gastroenterology and Hepatology. 2025;22(1):54-70.
4. Delzenne NM, Bindels LB. The prebiotic concept in nutrition is celebrating its 30th anniversary. The magazine for nutrition. 2025;155(7):2007-2008.