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Investigating microbiota of the gut-brain axis and the impact of cocaine

研究肠脑轴的微生物群和可卡因的影响

基本信息

批准号：
10625082
负责人：
Gulnaz Javan
金额：
$ 12.34万
依托单位：
ALABAMA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10625082
关键词：
Actinobacteria class Addictive Behavior Adrenal Glands Adverse effects Affect African African American African American population Age Alabama American Analysis of Variance Autopsy Bacteria Bacteroidetes Basal Ganglia Bioinformatics Biological Markers Blood - brain barrier anatomy Body mass index Brain Cadaver Caring Cells Cerebrum Cessation of life Characteristics Chloroform Chronic Cocaine Cocaine Abuse Cocaine Dependence Colon Communication Data Death Rate Determination of Death Development Disease Disparity Distal Double-Blind Method Drug Addiction Educational workshop Endocrine system Ensure Evaluation Farm Fentanyl Firmicutes Florida Future Goals Grant Health Homeostasis Human Hypothalamic structure Illicit Drugs Individual Intoxication Investigation Knowledge Leaky Gut Link Location Mediating Medical Metagenomics Microbe Mood Disorders Organ Overdose Pathogenesis Personal Satisfaction Persons Pharmaceutical Preparations Pharmacotherapy Phenols Pilot Projects Pituitary Gland Play Polymerase Chain Reaction Population Predisposition Process Productivity Proliferating Proteobacteria Race Reproducibility Research Personnel Risk Risk Factors Role Sampling Science Single-Blind Study Site Specimen Sterility Substance Use Disorder Systems Analysis Tennessee Testing Texas Tissue Extracts Tissues Transverse colon United States Universities Work addiction career cocaine overdose cocaine use cost drug of abuse emotional behavior experience gut dysbiosis gut microbes gut microbiome gut microbiota gut-brain axis human tissue ileum innovation insight knowledgebase mathematical model metabolomics microbial microbial composition microbial signature microbiome microbiota microbiota-gut-brain axis microorganism mortality novel novel diagnostics prevent receptor binding sex therapeutic target undergraduate student virtual

项目摘要

PROJECT SUMMARY / ABSTRACT Cocaine abuse continues to be a national crisis, with the cost of addiction to illegal drugs in the United States related to criminal activity, lost work productivity, and medical care totaling more than $740 billion per year. In particular, African-Americans, who make up 13.4% of the U.S. population, disproportionately bear the burden of cocaine use and overdoses. Multiple studies have shown that prolonged use of cocaine affects the gut microbiota, which in turn alters hypothalamus-pituitary-axis activity and emotional behavior. Cocaine-related studies have shown that drugs of abuse trigger preferential proliferation of gram-positive Firmicutes and reduction of gram- negative Bacteroidetes, results that are consistent with microbiota associations with drug addiction. Accumulating evidence also shows that gut microorganisms influence the bidirectional communication along the gut- brain axis, which indicates the crucial role of the gut microbiota on cocaine. Since evidence exists for the influence of commonly abused drugs on the microbiota gut-brain axis, the transverse colon, the distal ileum, the basal ganglia, and the pituitary and adrenal glands may have potential roles as biomarkers, specifically in overdose cases, due to the damage to these tissues caused by cocaine abuse. In this proposal, we will address the impact that cocaine has on the microbiota of the gut-brain axis. Our approach will allow for evaluation of microbial signatures in microbiota gut-brain axis-associated tissues using specimens extracted from cocaine overdose cadavers, an approach that previous studies have not used but could provide information that helps determine how people respond differently to cocaine, allowing researchers to better examine the potential adverse effects of microbes. Specifically, we will test the hypothesis that there is a significant association between gut microbiota and the gut-brain axis in cocaine overdose cases from three Southern regions - Alabama, Florida, and Tennessee. To test this hypothesis, we will (1) determine whether the gut microbiome that is associated with the transverse colon and distal ileum mediates the relationship between cocaine use and lethal drug intoxication in African Americans from Southern regions of the United States; (2) determine whether the gut microbiome that is associated with the basal ganglia and the pituitary and adrenal glands mediates the relationship between cocaine use and lethal drug intoxication in African Americans from Southern regions of the United States;; and (3) validate a mathematical model of specific microbial biomarkers in single-blind studies using African-American tissues to increase confidence and demonstrate reproducibility. These processes will be evaluated and validated to provide a basis for new diagnostics as well as therapeutic targets to prevent intentional and unintentional cocaine overdose with the long-term objective of restoring gut microbiome homeostasis. In addition, the hands-on experience that the undergraduate students gain conducting phenol-chloroform extractions, polymerase chain reaction, and the workshop at the Freeman Ranch Body Farm at Texas State University in this project will provide them with insights into whether an academic career in biomedical sciences might be an avenue they want to further pursue.

项目摘要/摘要