Scientists propose roadmap to unlock EU prebiotic health claims amid research gaps

Scientists have outlined a new strategic roadmap for prebiotic health claims to gain regulatory recognition in food and supplements in the EU. Currently, the term prebiotics has not been authorized in the region for use as a health claim, nor are there recommendations on how to achieve this. 

The paper in Gut Microbes suggests prebiotic substances must be characterized under in vitro and in vivo conditions using state-of-the-art research methods. Next, they note that selective microbiota modulation should be associated with a “demonstrable physiological benefit” and linked mechanistically to that benefit. 

Finally, the authors stress the importance of documentation, proving the cause-and-effect relationship between the prebiotic effect on the microbiota and the physiological benefit in the target population in multiple clinical studies. 

The paper, authored by the Prebiotics Task Force from the International Life Sciences Institute (ILSI) Europe, results from a workshop organized by the task force in October 2023 with experts from academia, industry and regulatory authorities. 

“Guidelines for a prebiotic health claim for food ingredients by a regulatory body like the European Food Safety Authority (EFSA) are so important as they will give consumers trust and credibility that the healthy food product has been scientifically validated,” says co-author Elaine Vaughan, health science and regulatory affairs leader from Sensus, a Dutch supplier of prebiotic chicory root fiber.

“In addition, approved health claims can educate consumers about the benefits of proven prebiotics and stimulate investment in innovation by the food industry in further healthier food products, which ultimately contributes to consumer and public health.”

The paper provides an overview of regulatory requirements for health claims, key findings from prebiotic research, research gaps and documentation challenges to achieving an EU health claim. 

Documentation hurdles

Although some prebiotic fibers, such as sugar beet fiber, hold health claims, the term “prebiotic” is not authorized as a health claim by EFSA. The agency has set strict criteria for approving health claims, requiring robust scientific evidence. The paper details that EFSA requires documentation of a prebiotic-driven change in the microbiota to provide “direct evidence of a physiological benefit that can be measured in vivo in humans.” 

The authors note this is a significant barrier to integrating prebiotics in a specific health claim. 

A well-substantiated health claim application needs at least two studies to investigate the conditions of use, such as the dose required in a food or supplement, to obtain an effect. Moreover, documentation must show that the prebiotic is bioavailable in the microbiota and provide evidence of a plausible mode of action. 

According to the authors, “standardized protocols, validated biomarkers and advanced data integration and analysis tools” are urgently needed to support study designs and overcome research gaps.

The proposed roadmap highlights research areas, gaps and documentation challenges to overcome (Image credit: ILSI Europe).Establishing a health claims dossier

The team is also aiming to build a European health claims dossier that outlines how prebiotics are linked to various health benefits. Considering existing scientific literature, the team highlights cognitive, immune, metabolic and digestive health as key research areas. 

The paper identifies three current research gaps and documentation challenges for prebiotics — namely, their mechanisms of action, “structure/function relationship” (mapping influencing factors like host diet and age) and overall cause-and-effect on host health. 

The authors note that the consensus panel behind the International Scientific Association for Probiotics and Prebiotics (ISAPP) 2017 definition of prebiotics also agrees on these benefits. 

At the same time, the ISAPP panel cautions that documenting the relationship between a prebiotic-mediated change in microorganisms and an observed health effect remains challenging.

“This review presents a clear and concise summary of the prebiotic concept and gives a balanced discussion as to their potential health effects in relation to gut, immune and metabolic health and cognitive function,” says lead author and expert group chair Kieran Tuohy from the University of Leeds, UK.

“It identifies gaps in current understanding of how prebiotics work and discusses the current regulatory challenges at length. As a cross-sector expert prebiotic sandpit report, it brings together key insights from academic and industrial stakeholders. It serves the community well in communicating the current state of play in terms of prebiotics as efficacious functional ingredients.”

For an EU health claim, prebiotic-driven change must provide direct evidence of a physiological benefit that can be measured in humans.Overcoming research gaps

The paper’s authors note that some prebiotics, such as inulin, lactitol, sugar beet fiber and rye fiber, have attained EU-authorized health claim status in digestive health. However, many other digestive health claim applications have not yet succeeded, as research has not established a cause-and-effect relationship. 

In a few cases, EFSA’s scientific opinion has made a mechanistic link between a prebiotic — namely chicory inulin — the gut microbiota and a digestive benefit. For example, the authority notes that this prebiotic fiber “may exert an effect on stool frequency by stimulating bacterial growth in the gut and increasing fecal bulk.” 

Although there is growing awareness and research linking the gut to immunity, the paper cautions there is insufficient evidence to meet an EU health claim for prebiotics’ impact on the immune system. An ILSI Europe expert group is evaluating the documented effects of prebiotics on immunity, inflammation and infection from randomized-controlled trials in humans. 

Regarding metabolic health, the paper concludes that findings linking dietary fibers and specific prebiotics to metabolic health are in harmony with the EFSA recommendation for a high-fiber diet. “However, more knowledge of the gut microbiota and the modulating effect of short-chain fatty acids is necessary to define specific prebiotic benefits for metabolic health in different metabolic subgroups.”

Many studies on the gut-brain axis support the gut microbiome’s association with psychiatric and cognitive dysfunction. However, the mechanisms behind probiotic effects on cognition are “poorly understood,” according to the paper. Last month, researchers also called for more rigorous research to validate promising probiotic effects. 

ILSI Europe experts on prebiotics and cognition highlight the importance of assessing relevant biomarkers and potential mechanisms of action to identify successful prebiotic interventions in terms of type, dose, timing and duration.