The Microbiome’s Influence on Substance Abuse and Treatment

The will is truly free, when it is not the slave of vices and sins. —Saint Augustine

It was historically believed that humans tend toward evil behaviors.

It has been accepted in Christian culture that humans are born sinful and naturally inclined toward villainy. The original sin was transmitted hereditarily from generation to generation. In his 2016 book, Born Bad, James Boyce argues that the Western mind is deeply rooted in the concept of eternal sinfulness. Descartes, Hume, Hobbes, Adam Smith, and others considered human nature to be inherently flawed, and the roots of this idea can be traced back to Augustine.

Today, we know that we are not entirely guilty of our sinful behavior. Our genome and microbiome play a major role in our behavior, including negative or harmful actions. A large number of studies have suggested that alterations in the gut microbiome may contribute to the onset and maintenance of addictive behaviors. Several genetic variations have been found in the dopaminergic reward system that make individuals susceptible to behavioral addictions and substance use disorders (SUDs) including the use of cocaine, opioids, and alcohol. Genetic variations in the genes responsible for alcohol metabolism also exist in individuals with alcohol addiction. Some genetic variations in neurotransmitter receptors or enzymes that metabolize them have been observed to be associated with susceptibility to SUDs. There is evidence suggesting that certain genes may be linked to cigarette smoking, including genetic susceptibility of nicotinic receptors. However, studies on homozygote twins have shown that the genome cannot fully explain all aspects of substance addiction. Other factors, such as socio-economic status and environmental factors, should contribute to the development of addiction.

The microbiome affects all aspects of our brain-derived tendencies.

The gut microbiome, which refers to the community of microorganisms living in the digestive tract, plays a crucial role in human physiology and pathology. One of the most intriguing aspects of gut microbiota is its impact on brain function, which is commonly referred to as the gut-brain axis. The intestinal microbiota has an impact on our mood, memory, learning, beliefs, and decision-making. It has been suggested that alterations in the normal balance of microorganisms or dysbiosis may affect our tendency towards certain types of foods, such as those that are rich in fat and carbohydrates. Recent studies have proposed that these microbes may also influence our other behaviors and inclinations.

Several mechanisms have been proposed to explain the reciprocal interactions between the brain and gut microbiota. These mechanisms include communication through nervous fibers and biochemical metabolites. Biochemical compounds can be produced either through microbial fermentation or directly by the gut microbiome. For instance, the microbiome has the ability to synthesize neuroactive compounds such as neurotransmitters. The cognitive effects of gut microbiota depend heavily on the types of microbial populations. Dysbiosis can alter the microbiome's products and, consequently, brain functions. In recent years, there has been a growing interest in the potential role of the microbiome in drug and substance addiction. Since studying the role of the intestinal microbiome on SUDs is challenging due to uncontrolled variables such as diet and genotypes, most of the findings have been obtained through animal models. Nevertheless, the results are fascinating. For instance, a study has revealed that mice with a disrupted gut microbiome are more susceptible to cocaine addiction compared to mice with a healthy microbiome. The researchers observed that disrupting the microbiome led to changes in the expression of genes involved in dopamine signaling. This neurotransmission system is crucial and has been linked to addiction. Another study found that mice with a disrupted microbiome exhibit an increased preference for consumption of alcohol compared to mice with a healthy microbiome. Transplanting fecal microbes from heavy drinkers into the intestines of non-drinkers can lead to a preference for alcohol in the recipients. Another study also revealed that transplanting fecal matter from opioid-exposed mice into healthy mice resulted in increased opioid-seeking behavior.

On the other hand, chronic usage of drugs and alcohol alters the intestinal ecosystem and balance of microbiota. For instance, opioids and alcohol consumption impair the permeability of the epithelial barrier, leading to increased exposure of the immune system to bacterial antigens. The immune response to these antigens results in a pro-inflammatory environment. There is evidence that chronic exposure to opioids altered the gut microbiome in mice with unknown mechanism.

The microbiome is a new target for the treatment of SUD.

Overall, although these studies suggest that the microbiome may have a significant impact on addiction, the precise mechanisms that underlie these effects are not yet entirely comprehended. One possibility is that changes in the microbiome can impact the production of neurotransmitters, including dopamine, leading to alterations in motivation and reward processing. Another possibility is that changes in the microbiome can affect inflammation and immune function, both of which have also been associated with addiction. Although further research is necessary to fully comprehend the microbiome's role in addiction, these findings emphasize the potential significance of considering the gut-brain axis in addiction prevention and treatment. For instance, the use of probiotics or microbiome-derived products such as short-chain fatty acids in supplement form can be considered as adjuvant therapy in the treatment of substance addictions, in conjunction with conventional medications.