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