Large-scale prebiotic trial targets mental wellness via gut-brain link

Radicle Science and Holobiome have launched a two-year study, Gut-Feelings, to explore prebiotics for mental wellness and map the gut microbiome. The trial will involve 6,000 participants testing 19 prebiotic interventions against a placebo to assess their impact on anxiety across different populations.

In an interview, Jeff Chen, MD, MBA, and CEO of Radicle Science, discussed the trial’s objectives. Chen emphasized the urgency of addressing the current mental health crisis with accessible solutions. “We wanted something rapidly deployable, affordable, and accessible, and we realized that food was the most efficient way to achieve that,” he said.

Mapping the Gut-Brain Axis

The study focuses on the gut-brain axis, a key pathway for using food to influence mental health. Chen highlighted a knowledge gap in understanding which foods nourish specific microbes, their activities, and how these affect the body and brain.

The 16-week trial will randomly assign participants to receive one of 19 proprietary food-derived prebiotic formulas from Holobiome or a placebo. Instead of testing a single ingredient, the trial will evaluate multiple formulas, as Chen believes different prebiotics may benefit various individuals based on their unique microbiomes.

Chen explained, “This notion of precision food for precision mental wellness is achievable when you can do 19 trials’ worth of data collection and interventions in one, with gold standard randomization, blinding, control, multiplicity corrections, validated outcomes.”

The trial will also create a new model, Mercator, to understand how the gut microbiome interacts with biological processes related to mental wellness and beyond. This will involve collecting multi-omics data, including stool sequencing, blood proteomics, and digital omics from participants.

Historically, probiotics have been the focus of gut health research. However, this trial shifts attention to prebiotics—substances that nourish existing gut microbes. Chen noted that prebiotics may offer a more scalable and personalized approach compared to probiotics, which can be challenging to produce and stabilize.

Trial Design and Data Collection

Enrollment began in October 2026, with 6,000 diverse Americans participating in two waves. The trial is supported by the Advanced Research Projects Agency for Health within the US Department of Health and Human Services.

Participants will receive blinded sachet powders and will be instructed to incorporate them into their diet, such as by mixing them into yogurt. The trial features a ballooned placebo control group, with a higher number of participants in the placebo group for comparative analysis.

The decentralized design allows participants to collect biological samples at home, which Holobiome will analyze. They aim to collect and analyze over 24,000 fecal samples and 12,000 blood samples.

Researchers will also collect data from participants’ validated questionnaires and AI agents deployed in the study. Radicle Science will use its Reflexive Trials platform to manage the complex, multi-arm trial and integrate findings into R&D and marketing efforts.

The partnership with Holobiome leverages their Microbiome Vault, which contains the most diverse collection of human gut bacteria and a proprietary database mapping 120,000 human metagenomes to specific health states. This allows them to model microbiome effects and predict prebiotic impacts on metabolite production and microbial development.

Chen says that prebiotics may help achieve the goals of probiotics and postbiotics but in a more scalable, durable, and personalized way.

Chen concluded, “We can do scaled research to maintain rigor but dramatically lower the cost, improve the speed, and have real-world participants that are incredibly diverse using the products in real-world settings.” Initial results are expected in the second half of 2027.

Researchers will use validated surveys to measure anxiety, stress, mood, sleep quality, and overall quality of life. These surveys are considered the gold standard for assessing these aspects of mental health.

In addition to surveys, they will collect blood and stool samples for multi-omics analysis. This involves studying the genome, proteome, and metabolome to understand the complex interactions between the gut microbiome and human health.