Drugs and Bugs: The Gut-Brain Axis and Substance Use Disorders

Abstract

Substance use disorders (SUDs) represent a significant public health crisis. Worldwide, 5.4% of the global disease burden is attributed to SUDs and alcohol use, and many more use psychoactive substances recreationally. Often associated with comorbidities, SUDs result in changes to both brain function and physiological responses. Mounting evidence calls for a precision approach for the treatment and diagnosis of SUDs, and the gut microbiome is emerging as a contributor to such disorders. Over the last few centuries, modern lifestyles, diets, and medical care have altered the health of the microbes that live in and on our bodies; as we develop, our diets and lifestyle dictate which microbes flourish and which microbes vanish. An increase in antibiotic treatments, with many antibiotic interventions occurring early in life during the microbiome's normal development, transforms developing microbial communities. Links have been made between the microbiome and SUDs, and the microbiome and conditions that are often comorbid with SUDs such as anxiety, depression, pain, and stress. A better understanding of the mechanisms influencing behavioral changes and drug use is critical in developing novel treatments for SUDSs. Targeting the microbiome as a therapeutic and diagnostic tool is a promising avenue of exploration. This review will provide an overview of the role of the gut-brain axis in a wide range of SUDs, discuss host and microbe pathways that mediate changes in the brain’s response to drugs, and the microbes and related metabolites that impact behavior and health within the gut-brain axis. Graphic Abstract

Drugs, Guts, Brains, but Not Rock and Roll: The Need to Consider the Role of Gut Microbiota in Contemporary Mental Health and Wellness of Emerging Adults

“…For example, Shanahan et al found increased relative abundance of Firmcutes and Actinobacteria , with lower levels of Bacteroidetes ( Prevotella ) and Proteobacteria ( Neisseria ) [ 84 ]. Other studies have found an increase in Proteobacteria and Bacteroidetes , as well as Clostridia and Prevotella , in smokers [ 82 ]. The effects of nicotine on the GM may depend on the mode of intake and individual factors such as sex, diet, and genetics [ 82 ].…”

“…Other studies have found an increase in Proteobacteria and Bacteroidetes , as well as Clostridia and Prevotella , in smokers [ 82 ]. The effects of nicotine on the GM may depend on the mode of intake and individual factors such as sex, diet, and genetics [ 82 ].…”

“…The underlying mechanisms of nicotine effects on GM are largely unknown but are thought to involve increased permeability of intestinal mucosa and impaired mucosal immune responses [ 81 ]. These may occur via altered levels of SCFA and bile acids [ 82 , 83 ]. Nicotine use is associated with significantly lower bacterial diversity in the upper small intestinal mucosa [ 82 ].…”

“…These may occur via altered levels of SCFA and bile acids [ 82 , 83 ]. Nicotine use is associated with significantly lower bacterial diversity in the upper small intestinal mucosa [ 82 ]. However, conflicting microbial findings are reported in the literature on smoking and the GM [ 16 ].…”

“…Alcohol consumption is associated with reduced Bifidobacteria , Bacteroidetes , and Lactobacillus , and increased pro-inflammatory Proteobacteria in the gut [ 82 ]. Changes in the GM, along with an impaired intestinal barrier and mucosal inflammation secondary to excessive alcohol use, are thought to play a key role in the development and maintenance of alcohol use disorders as well as alcohol-related liver disease [ 82 ].…”