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

• 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
• 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

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 可卡因滥用仍然是一场国家危机，在美国对非法毒品的成瘾成本 与犯罪活动，工作生产率损失以及每年总计超过7400亿美元有关。在 特别是占美国人口13.4％的非裔美国人，不成比例地承担着 可卡因的使用和过量。多项研究表明，可卡因长期使用会影响肠道菌群， 这反过来改变了下丘脑 - 垂体 - 轴活动和情感行为。与可卡因有关的研究已有 表明滥用药物会触发革兰氏阳性富公司的优先增殖，并减少革兰氏阴性 阴性细菌群，与菌群与药物成瘾的关联一致的结果。累积 证据还表明，肠道微生物会影响沿肠道的双向交流 脑轴，表明肠道菌群在可卡因上的关键作用。由于存在影响的证据 在微生物核肠脑轴上常见的药物，横向结肠，远端，基础 神经节，垂体和肾上腺可能具有潜在的作用，特别是在 由于可卡因滥用造成的这些组织损害，过量的病例。在此提案中，我们将解决 可卡因对肠道轴的微生物群的影响。我们的方法将允许评估 使用可卡因提取的标本，微生物肠肠轴相关组织中的微生物特征 过量的尸体，这是以前研究尚未使用的方法，但可以提供可帮助的信息 确定人们对可卡因的反应方式不同，使研究人员能够更好地检查潜力 微生物的不利影响。具体而言，我们将检验以下假设： 来自三个南部地区的可卡因过量病例中的肠道菌群和肠脑轴 - 阿拉巴马州 佛罗里达州和田纳西州。为了检验该假设，我们将（1）确定是否是肠道微生物组 与横向结肠和远端回肠有关的可卡因使用与致命之间的关系 来自美国南部地区的非洲裔美国人的毒品中毒； （2）确定肠道是否 与基底神经节以及垂体和肾上腺相关的微生物组介导 来自南部地区的非裔美国人的可卡因使用与致命药物中毒之间的关系 美国;; （3）在单盲研究中验证特定微生物生物标志物的数学模型 使用非裔美国人组织提高信心并证明可重复性。这些过程将是 经过评估和验证，以提供新的诊断和治疗目标的基础，以防止有意 和无意可卡因的过量服用，其长期目标是恢复肠道微生物组稳态。在 此外，本科生获得苯酚 - 氯仿的实践经历 德克萨斯州弗里曼牧场的萃取，聚合酶链反应和车间 该项目中的大学将为他们提供有关生物医学学术生涯的见解 可能是他们想进一步追求的途径。