# Genetic Control of Addiction by Host and Microbiome

> **NIH NIH U01** · JACKSON LABORATORY · 2020 · $799,817

## Abstract

PROJECT SUMMARY/ABSTRACT
The overall long-term objective of this project is to understand the role of the microbiome and host genetics in
substance use disorders (SUD). SUD presents a significant and ongoing public health burden in our nation. In
2015, an estimated 20.8 million Americans aged 12 or older had alcohol or other drug use disorders, while
approximately 27.1 million people reported past-month illicit drug use. SUD are highly heritable. Indeed, a
number of genes have been identified as associated with addiction using candidate gene approaches and
GWAS approaches. However, genes identified so far only account for a small proportion of the genetic
variants. Accumulating evidence suggests that the gut microbiome plays a significant role in behavioral
response to cocaine, as well as anxiety- and depression-like behaviors, many of which are comorbid with
addiction. Our preliminary data demonstrates that there is a relationship between the microbiome and addictive
behavior. Host genetics can influence the composition of the gut microbiome. The heritability of the gut
microbiome is evident from both animal and human studies. In this proposed study, we aim to reveal an
integrated genetic basis of addiction that combines host genetics and the microbiome. To achieve this goal, we
will leverage our expertise in mouse behavioral genetics, the gut microbiome and also leverage an ongoing
project with a collection of Diversity Outbred (DO) samples and phenotyping data to test our hypothesis that
the interplay of host genetics and the gut microbiome drives drug addiction. In Specific Aim 1, we will identify
genetic loci that control the abundance gut microbiome and overlapping loci between the gut microbiome and
novelty related behaviors. In Specific Aim 2, we will identify genetic loci that control addiction in the setting of
cocaine exposure using the intravenous drug self-administration (IVSA) system, and also identify overlapping
loci between the microbiome and IVSA behaviors. The association of abundance of the microbiome with
novelty related behaviors in Aim 1 and IVSA behaviors in Aim 2 will also be determined. In Specific Aim 3, we
will construct the gene expression network in the brain and gut, and integrate the network with the microbiome
members and metabolic pathways at transcription level. Altogether, our proposed project will be the first to
delineate the genetic basis of drug addiction by integrating host genetics and the gut microbiome. If our
hypothesis is confirmed, it is likely to lead to the discovery of a novel mechanism of drug addiction and provide
novel therapeutic targets for addiction.

## Key facts

- **NIH application ID:** 9985773
- **Project number:** 5U01DA043809-03
- **Recipient organization:** JACKSON LABORATORY
- **Principal Investigator:** Jason A Bubier
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $799,817
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9985773

## Citation

> US National Institutes of Health, RePORTER application 9985773, Genetic Control of Addiction by Host and Microbiome (5U01DA043809-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9985773. Licensed CC0.

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