# A Model of Antibiotic-induced Gut Dysbiosis and Depressive Symptomatology

> **NIH NIH K01** · UNIVERSITY OF NEBRASKA OMAHA · 2024 · $126,738

## Abstract

PROJECT SUMMARY
Emerging microbiota-gut-brain axis research demonstrates an important role of gut microbes in the
establishment and treatment of nervous system disorders, including depression. An estimated 300 million or
nearly 4% of the human population suffers from depression globally. Depression is a complex multifactorial
disease and recent epidemiological studies indicate that antibiotic treatment predisposes humans to the
development of neuropsychiatric disorders, including depression. One proposed mechanism is that antibiotic
administration alters gut microbiome structure and function as well as hinders gut-brain communication through
decreased synthesis of neuroactive compounds. However, the mechanisms by which antibiotics induce
depression remain unclear. In this K01 award proposal, I propose to use a novel nonhuman primate model, the
common marmoset (Callithrix jacchus), to investigate the mechanisms by which antibiotics induce depression.
Marmosets serve as a powerful model due to their human-like similarity in physiological and behavioral sequelae.
My specific aims are as follows: 1. Characterize changes in gut microbiome structure and function as well as
behavior in marmosets following antibiotic treatment, 2. Evaluate the additive effect of antibiotic treatment and
social separation on induction of depressive symptomatology in marmosets, and 3. Evaluate the therapeutic
effect of fecal microbiota transplantation on treatment of depression in antibiotic-induced dysbiotic marmosets. I
plan to administer a broad-spectrum antibiotic cocktail (with and without additional stressors) and study changes
in behavior, immune profiles, neuroendocrine hormone levels, gut microbiome structure and function and gut
bacterial metabolites. I also plan to study the role of fecal microbiota transplantation in reversing behavioral,
physiological and microbiological changes in marmosets administered antibiotics and compare its efficacy to
fluoxetine (a commonly prescribed antidepressant). The results from this research will generate novel
hypotheses, serve as critical preliminary data necessary to compete for competitive extramural funding, and
represent the first step towards establishing the common marmoset as a translational model for studying effects
of antibiotic use on microbiome modulation and the development of depression. I have also established a training
plan and mentorship team to gain critical skills in neurobiology, metabolomics and multi-omics data analysis. My
long term goal is to become a leader in microbiota-gut-brain axis research and to establish marmosets as an
animal model to study the role of gut-brain axis communication in neuropsychiatric disorders.

## Key facts

- **NIH application ID:** 10823247
- **Project number:** 5K01OD030514-03
- **Recipient organization:** UNIVERSITY OF NEBRASKA OMAHA
- **Principal Investigator:** Jonathan Brent Clayton
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $126,738
- **Award type:** 5
- **Project period:** 2022-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10823247

## Citation

> US National Institutes of Health, RePORTER application 10823247, A Model of Antibiotic-induced Gut Dysbiosis and Depressive Symptomatology (5K01OD030514-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10823247. Licensed CC0.

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