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A Model of Antibiotic-induced Gut Dysbiosis and Depressive Symptomatology

Award Number: K01OD030514
ORGANIZATION: OFFICE OF THE DIRECTOR, NIH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 04/01/2022
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $96,317 )
2026	2026	UNIVERSITY OF NEBRASKA	6001 DODGE ST EAB 209	OMAHA	NE	68182	DOUGLAS	USA	Research Infrastructure Programs	000	5	4/2/2026	NON-COMPETING CONTINUATION	$96,317
														Subtotal = $96,317

Issue Date FY: 2025 ( Subtotal = $126,738 )
2025	2025	UNIVERSITY OF NEBRASKA	6001 DODGE ST EAB 209	OMAHA	NE	68182	DOUGLAS	USA	Research Infrastructure Programs	000	4	4/23/2025	NON-COMPETING CONTINUATION	$126,738
														Subtotal = $126,738

Issue Date FY: 2024 ( Subtotal = $126,738 )
2024	2024	UNIVERSITY OF NEBRASKA	6001 DODGE ST EAB 209	OMAHA	NE	68182	DOUGLAS	USA	Research Infrastructure Programs	000	3	3/13/2024	NON-COMPETING CONTINUATION	$98,092
2024	2024	UNIVERSITY OF NEBRASKA	6001 DODGE ST EAB 209	OMAHA	NE	68182	DOUGLAS	USA	Research Infrastructure Programs	002	3	5/21/2024	NON-COMPETING CONTINUATION	$17,747
2024	2024	UNIVERSITY OF NEBRASKA	6001 DODGE ST EAB 209	OMAHA	NE	68182	DOUGLAS	USA	Research Infrastructure Programs	001	3	5/14/2024	NON-COMPETING CONTINUATION	$10,899
														Subtotal = $126,738

Issue Date FY: 2023 ( Subtotal = $126,738 )
2023	2023	UNIVERSITY OF NEBRASKA	6001 DODGE ST EAB 209	OMAHA	NE	68182	DOUGLAS	USA	Research Infrastructure Programs	000	2	4/6/2023	NON-COMPETING CONTINUATION	$126,738
														Subtotal = $126,738

Issue Date FY: 2022 ( Subtotal = $126,738 )
2022	2022	UNIVERSITY OF NEBRASKA	6001 DODGE ST EAB 209	OMAHA	NE	68182	DOUGLAS	USA	Research Infrastructure Programs	001	1	5/7/2022	NEW	$12,674
2022	2022	UNIVERSITY OF NEBRASKA	6001 DODGE ST EAB 209	OMAHA	NE	68182	DOUGLAS	USA	Research Infrastructure Programs	000	1	3/15/2022	NEW	$114,064
														Subtotal = $126,738

Grand Total All Awards = $603,269

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A Model of Antibiotic-induced Gut Dysbiosis and Depressive Symptomatology

Award Number: K01OD030514

ORGANIZATION: OFFICE OF THE DIRECTOR, NIH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 04/01/2022

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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