Microbiome and substances of abuse

There is a growing amount of evidence showing a reciprocal relation between the gut microbiota and the brain. Substance use disorders (SUD), which are a major cause of preventable morbidity and mortality worldwide, have an influence on the gut microbiota and on the gut-brain axis. The communication between the microbiota and the brain exists through different pathways: (1) the immune response elicited by bacterial products, coupled with alterations of the intestinal barrier allowing these products to enter the bloodstream, (2) the direct and indirect effects of bacterial metabolites such as short chain fatty acids (SCFAs) or tryptophan on the brain, (3) and the hypothalamic-pituitary-adrenal (HPA) axis, whose peripheral afferents can be influenced by the microbiota, and can in turn activate microglia. Among substances of abuse, alcohol has been the subject of the greatest number of studies in this field. In some but not all patients suffering from alcohol-use-disorder (AUD), alcohol alters the composition of the gut microbiota and the permeability of the intestinal barrier, directly and through dysbiosis. It has also been well demonstrated that alcohol induces a peripheral inflammation; it is still unclear whether it induces a central inflammation, as there are contradictory results in human studies. In animal studies, it has been shown that neuroinflammation increases during alcohol withdrawal. Literature on opioids and stimulants is less numerous. Chronic morphine intake induces dysbiosis, increased intestinal permeability and a probable neuroinflammation, which could explain symptoms such as tolerance, hyperalgesia and deficit in reward behavior. Cocaine induces a dysbiosis and conversely the microbiome can modulate the behavioral response to stimulant drugs. Tobacco cessation is associated with an increase in microbiota diversity. Taken together, the findings of our narrative literature review suggest a bidirectional influence in the pathogenesis of substance use disorders.

Keywords: Alcohol-use-disorder; Gut microbiota; Gut-brain axis; Inflammation; Intestinal permeability; Opioids; Stimulants; Substances of abuse.