The GUT-FEELINGS study is a two-year research initiative supported in part by the Advanced Research Projects Agency for Health (ARPA-H). It will test 19 food-derived prebiotic formulations against a placebo, with initial results expected in the second half of 2027.
The researchers aim to identify which interventions may improve feelings of anxiety and related mental wellness outcomes, and which populations are most likely to respond.
Jeff Chen, MD, co-founder and CEO of Radicle Science, said the study will investigate the relationship between prebiotic intake, changes in the gut microbiome and resulting health outcomes.
“When it comes to the gut-brain connection, what we don’t fully understand are which gut microbes, when fed which types of prebiotics, carry out what sorts of functions, produce what sorts of postbiotics, change what happens in the human body that can then lead to functional outcome measures and other health outcomes,” he said.
The study will combine randomized, placebo-controlled testing with in-depth stool sequencing and blood proteomics to investigate how the interventions affect the microbiome and the body.
Researchers will also collect participant-reported outcomes and digital and behavioral data, including information from wearables and continuous glucose monitors. Measures will cover anxiety, stress, mood, sleep, quality of life and other health outcomes.
Moving towards precision wellness
Pelin Thorogood, co-founder and executive chairwoman of Radicle Science, said the scale of the study is important given the variability of the human microbiome.
“What’s really exciting about this study is not just the scale in terms of the number of people, but also the depth of the data we’re collecting,” she said.
The trial will enroll participants across all 50 states, allowing researchers to investigate differences in response across a diverse population. The aim is to understand not only whether an intervention works, but also who responds and how responders differ from non-responders.
Thorogood said the depth of data could provide a new level of insight into how different interventions affect different people.
“The depth of data across that many people actually gives us a level of resolution on how these interventions affect the different people at a level that has never been done before,” she said.
Participant diversity is another consideration in the trial, as researchers seek to understand how responses to prebiotic interventions may differ across populations. Radicle Science has previously studied nearly 100,000 Americans across its clinical trials, with Thorogood noting that its research has included over 50% women and people from rural communities with potentially different dietary and behavioral habits.
Implications for prebiotic products
The findings could help inform the development of more targeted prebiotic ingredients and products for mental wellness.
Chen said food-derived prebiotics that demonstrate efficacy could potentially be used as standalone powders or incorporated into foods, offering a route to broader consumer access.
Unlike probiotics, which introduce live microorganisms, prebiotics aim to support existing microbes in the gut. Understanding which prebiotic ingredients influence specific microbial populations could help researchers develop interventions tailored to different individuals.
Philip Strandwitz, PhD, CEO and co-founder of Holobiome, said the study aims to address a key evidence gap.
“The missing link is large-scale multimodal data from interventional studies, the kind this trial is designed to generate,” he said.
By testing 19 interventions in parallel, the researchers hope to advance understanding of the gut-brain axis and identify opportunities for more personalized approaches to mental wellness.
