# Multidisciplinary Characterization of the Gut-Brain Axis in Addiction

> **NIH NIH DP2** · RUTGERS, THE STATE UNIV OF N.J. · 2024 · $1,391,376

## Abstract

Project Summary
 Addiction and substance use disorders (SUDs) affect more than 27 million people in the United States,
with an estimated $740 billion annual cost due to crime, lost work productivity, and health care expenses.
Unfortunately, these numbers continue to increase and even more, since the pandemic, unleashing an alarming
health and social burden. Despite worldwide efforts, no successful treatments have been developed to better
deal with this chronic and relapsing disease. In the past years, the gut microbiota and its composition has been
associated with different adult behaviors and diverse neuropsychological diseases, including SUDs. However,
the mechanism by which the gut microbiota influences these pathologies remains elusive, with most of the
available data originating from associations between human patients or animal models and their fecal
microbiome profiles. There is an urgent need to push the field toward more mechanistic studies to find actual
communication pathways and molecular mediators behind these gut-brain connections. Therefore, the goal of
this project is to identify and characterize relevant interactions between different members of the gut microbiota,
psychostimulant exposure, and vulnerability to develop SUDs. To this end, we will apply a conceptually and
technically innovative approach that really bridges the fields of neuroscience and microbiology. We will use
metagenomics and metabolomics to identify psychostimulant-induced alteration in microbial composition and
gut milieu. We will then apply pharmacological and microbiological techniques to modulate gut physiology and
bacterial genetics to validate identified host signals and characterize bacteria-sensing pathways that are
impacted by the drug. To understand how the microbiome influences the progression to disease, we will combine
gut microbial manipulations with well-established animal models to determine the impact of these manipulations
on addiction. We will leverage the availability of genetically tractable hosts (mice) and human gut bacterial strains
to build up in vitro and in vivo models that will allow us to better understand the molecular mechanisms involved
in this interkingdom communication. This project is only possible because we have developed the protocols and
the technical resources to accurately manipulate and investigate bacterial physiology while also following
neurobehavioral alterations associated with psychiatric diseases. We have the experience and the equipment to
run a battery of behavioral tests under microbiologically controlled conditions. Our approach provides an exciting
opportunity for acquiring new knowledge regarding addiction, gut microbiome physiology, and their interaction,
that can make a vertical leap in the field.
|Contact PD/PI: Cuesta, Santiago

## Key facts

- **NIH application ID:** 10908045
- **Project number:** 1DP2AT013279-01
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** Santiago Cuesta
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,391,376
- **Award type:** 1
- **Project period:** 2024-09-17 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10908045

## Citation

> US National Institutes of Health, RePORTER application 10908045, Multidisciplinary Characterization of the Gut-Brain Axis in Addiction (1DP2AT013279-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10908045. Licensed CC0.

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