The challenges of gut microbiome clinical trials, including individual variability, strain-specific effects and stringent regulatory standards, were spotlighted during a panel discussion at the recent Yakult symposium held in Amsterdam.
As Dr. Emily Prpa, science manager at Yakult UK and Ireland, explained during her introduction, there are multiple complexities to clinical trials in gut microbiome research.
Firstly, everyone’s microbiome is unique and is influenced by genetics, diet, lifestyle, stress and environment. This variability complicates clinical trials, as responses to probiotics or prebiotics can differ between participants.
Secondly, there can be issues with heterogeneity in research, as strain-specific effects and differences between products create variable results, making it difficult to demonstrate clear cause-and-effect relationships, “hampering efforts to gain regulatory approval for health claims.”
Finally, regulatory challenges offer another barrier. While demonstration of an effect in the general population is required, especially under European Food Safety Authority (EFSA) standards, proving efficacy is often easier in at-risk subpopulations.
This often means that claims may not apply to the general population, Prpa said.
What does EFSA look for?
Professor Hans Verhagen, food safety and nutrition consultant, noted that it is necessary to frame the right question when addressing nutritional research challenges to achieve EFSA approval.
“Many health claims fail to meet standards,” he said. “The key to increasing claim approval will be prioritizing precise research questions, gathering robust data and ensuring experiments are well-structured, rather than over-emphasizing mechanism of actions.”
This, Verhagen explained, should ensure that the research is directed toward achieving meaningful and specific outcomes.
“In my experience, particularly during my work with EFSA on health claims regulation, the focus was always on asking the right questions and ensuring scientific rigor,” he added.
“The fundamental question remains—does it work? If it doesn’t, no study design will save it. Science must rely on evidence, not belief.”
However, researchers in the space increasingly face a significant conflict between academic and regulatory expectations, noted Professor Karen Scott from the University of Aberdeen.
Commenting from the audience, Scott said that academic researchers are pressured to publish novel studies in high-impact journals, while regulatory bodies like EFSA prioritize reproducibility through repeated studies.
This creates a challenge, as the industry often funds repeated studies, leading to skepticism about data integrity. Resolving this issue is clearly crucial, but until a solution is found, progress remains hindered, she said.
Practicing good science
The key to good science, particularly in the field of nutrition research, lies in rigor and transparency, said Professor Wendy Hall from Kings College, London.
“Pre-registering trials, clearly identifying primary outcomes and following strict reporting guidelines to enhance data reliability and facilitate meta-analyses is imperative,” she noted.
However, there is an inherent complexity to nutrition research, such as studying whole foods and systems like the microbiome. Hall said this requires collaborative efforts from across the industry to address.
Dr. Gwen Falony, research manager at University Medical Center Mainz, commented that effective research requires a hypothesis-driven approach, mirroring Verhagen’s point. He added that focused questions from the outset may be able to reduce sample size needs and minimize statistical errors in studies.
He also noted that identifying “unhealthy microbiota” is going to be essential for the future of disease prevention.
This will require focusing on key factors such as microbial diversity, microbial load and resistance—either to antibiotics or external changes.
Consumer communication
The science alone is not enough, according to Dr. Bruno Pot, science manager for Yakult Europe.
“The real obstacle is translating research findings into consumer communication,” he said, accrediting this obstacle to market confusion and regulatory barriers.
Pot questioned whether the industry is missing opportunities to connect with consumers about potential health benefits.
He proposed exploring alternative methods to assess the health benefits of foods beyond expensive and time-consuming clinical trials.
Instead, approaches like cohort studies or Mendelian randomization could help the food industry better support claims and offer evidence to support long-term effects without strict clinical trials, Pot said.
