Addiction Research Should Go with the Gut

Addiction Research Should Go with the Gut

by Vincenzo Montoni | Edited by Evan DeTurk

Pathological substance use is a profoundly pressing health crisis in the United States and across the world. Researchers have worked tirelessly to keep pace with the crisis and have learned much about neuronal signaling networks as well as intracellular signaling cascades associated with prolonged drug use. Nonetheless, sufficient treatment methods for Substance Use Disorder (SUD) are still sorely lacking, and researchers are actively searching for new ways to treat this crisis. The gut microbiome represents a promising new frontier for such research inquiry. 

Research of the gut microbiome and its relationship with addiction is still new and expanding, but several recent studies have demonstrated a worrisome conflation of gut microbiome characteristics and addiction levels. For instance, a 2016 study from the lab of Dr. Drew Kiraly of the Icahn School of Medicine investigated whether alterations of the host microbiome in mice due to cocaine could affect behavioral responses of the mice. Prior to this work, several studies had been published on gut-brain connections in mood, anxiety, and autism-related disorders, but no study had specifically investigated gut-brain connections related to substance use. The Kiraly lab accordingly began research in this unexplored area by investigating the response of gut microbiota to cocaine and the ways in which these microbiota might impact drug-mediated behaviors. To accomplish this, Kiraly’s lab gave adult mice a cocktail of antibiotics in their drinking water for 7–10 days before the start of cocaine treatments, a procedure known to markedly reduce gut bacteria. After accounting for all other variables, they provided mice with high-level and low-level doses of cocaine. For the low-level doses, the mice with reduced gut bacteria due to treatment with antibiotics reacted much more significantly to the cocaine and demonstrated a much more robust preference. 

The experiment therefore demonstrated “a significant shift in the dose-response curve for the rewarding properties of cocaine in mice with reduced intestinal bacteria.” In other words, it appears that the gut microbiome and its interactions with the brain are important for development of cocaine reward associations as well as behavioral responses to cocaine. The actual mechanisms by which the gut microbiome impacts drug-mediated behavior were not fully clarified in this experiment, but the experiment’s discovery of the relationship between the gut microbiome and addiction behavior in mice provides a novel target for potential treatment interventions to improve treatment outcomes in drug addicted individuals. 

Interestingly, researchers at Princeton University, including Dr. Mohamed Dania of the Molecular Biology department, are actively engaged in various studies of the gut microbiome. However, research specifically on the relationship between addictive substances and the gut microbiome is not currently being performed at Princeton. Because the research from the Kiraly Lab presents the gut microbiome as a promising new avenue for addiction research, more research in this area — at Princeton or abroad — is certainly warranted. 

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