# Administrative Supplement to Probiotic Administration for Adolescent Depression

> **NIH NIH R61** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $104,973

## Abstract

PROJECT SUMMARY/ABSTRACT. Adolescence is a sensitive developmental period in which prevalence
rates of depression sharply increase. Our current first-line treatments are often ineffective in achieving clinical
remission in adolescents with depression. Thus, given the poor mental and physical health outcomes
associated with adolescent-onset depression, new interventions are urgently needed for the treatment of this
debilitating condition. Probiotics, dietary supplements consisting of live beneficial bacteria that can improve
dysbiosis of the gut microbiota, are a promising treatment for adolescent depression. While there is no
consensus in the scientific literature supporting which probiotic to administer since current probiotic
formulations consist of various different bacterial strains and species, research suggests that multi-strain
probiotics may be more efficacious than single-strain probiotics in preventing and treating gut dysbiosis.
Therefore, the primary objective is to study adolescents diagnosed with a clinical depressive disorder
undergoing Visbiome®, a multi-strain probiotic, treatment to determine changes in two biological signatures: (1)
the left hippocampus–precuneus (HP) resting-state functional connectivity (RSFC) of the brain and (2)
Lactobacillus abundance of the gut microbiome (bacteria and other microorganisms and their genetic materials
that reside in the gastrointestinal tract). The central hypothesis is based on the gut-brain axis, where the gut
microbiome influences the hippocampus and precuneus, and thus depression. Guided by published literature
and strong preliminary data, this hypothesis will be tested by studying changes in the left HP RSFC, gut
microbiome, and depressive symptoms in two randomized controlled trials (RCTs). The R61 phase will consist
of 77 depressed adolescents randomized to either Visbiome® 450 billion CFU bacteria twice daily group or
placebo twice daily group. The R33 phase will consist of 77 depressed adolescents randomized to one of
three groups: (1) Visbiome® 450 billion CFU bacteria twice daily, (2) Visbiome® 900 billion CFU bacteria twice
daily, or (3) placebo twice daily group. “Go/No-Go Criterion”: To advance from the R61 to R33 phase, the
probiotic group vs. placebo group must meet the following effect size threshold for either the left HP RSFC or
Lactobacillus: ηp2 ≥ 0.06 (p<0.05). The R33 phase will also collect data to help determine the optimal dose of
probiotics for a subsequent larger efficacy trial. The proposed research is innovative because it will inform the
design of a future efficacy trial that has the potential to change clinical practice or practice guidelines. The
proposed research is significant since it is expected to greatly advance our knowledge and understanding of
the underlying mechanism by which probiotics improve depressive symptoms in adolescents, which will
ultimately inform the treatment and prevention of adolescent depression.

## Key facts

- **NIH application ID:** 11046396
- **Project number:** 3R61AT012028-01A1S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Cherry Leung
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $104,973
- **Award type:** 3
- **Project period:** 2023-09-18 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11046396

## Citation

> US National Institutes of Health, RePORTER application 11046396, Administrative Supplement to Probiotic Administration for Adolescent Depression (3R61AT012028-01A1S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11046396. Licensed CC0.

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