The Gut Microbiome and Addiction — Is There A Connection?


Researchers in addiction science search for the biological and physiological mechanisms that contribute to addiction every day. They perform studies with human subjects, studies on laboratory animals, and studies on the microscopic level in test tubes and petri dishes. They strive to identify the physical mechanisms that may cause addiction and facilitate the maintenance of addiction — i.e. chronic use of alcohol and drugs — to support the work done by the behavioral health professionals who treat and support people seeking sobriety, abstinence, and long-term recovery. They also hope that in identifying the mechanisms behind addiction, they can prevent or reduce the risk of people developing an alcohol or substance use disorder — what we now call alcoholism or drug abuse — in the first place.

To date, most of the research on the physical mechanisms of addiction has involved detailed studies of the brain. That’s logical, because we know that substances of misuse cause both physiological and functional changes in the brain areas involved with reward and motivation. We also know that long-term exposure to substances of misuse degrades cognitive function, and in particular, impairs the executive decision-making processes that may otherwise keep an individual from continued alcohol or substance use.

Recently, however, some researchers shifted their point of focus from the brain to an area that most of us would never connect with a phenomenon like addiction: the gut microbiome. This article discusses the data presented in the peer reviewed journal article “A Potential Role for the Gut Microbiome in Substance Use Disorders” published by scientists from the Friedman Brain Institute at the Icahn School of Medicine in Mount Sinai, New York. All the factual details about the gut microbiome that follow come from that article.

What is the Gut Microbiome?

Here’s a fact we all know, and that, for lack of a better phrase, kind of grosses us all out: our digestive system is populated by little critters we call bacteria. A whole lot of bacteria. In fact, in the duodenum (part of the small intestine), scientists identify 100–10,000 bacterial cells per gram of tissue, and in the bowel contents of the large intestine (euphemism alert), they identify between 100,000,000,000 and 1,000,000,000,000 bacterial cell per gram. If you lost track of the zeros, that’s between one hundred billion and an even trillion bacterial cells per gram of bowel content (there’s that euphemism again).

That’s what the gut microbiome is: all the bacteria that live inside our digestive system. Our tummy critters. Collectively, the species found in the gut microbiome have what’s known as a genome, which refers to all the genes contained in the cytoplasm of the bacterial cells in the gut (bacterial cells do not have nuclei). The gut genome contains roughly ten million genes across the various bacterial species, compared to the 30,000 genes that make up the human genome. Put another way, the human genome has 0.3% of the genetic material contained within the gut genome.

We shouldn’t get a complex about that, though, because we are but one species, and each of us has — depending on the individual — anywhere from a hundred to a thousand distinct species of bacteria living in our digestive system.

In addition to participating in the process of breaking down our food and elimination waste from our bodies, the gut microbiome “promotes intestinal homeostasis…protecting the host from exogenous, pathogenic bacteria.” Translation: our helpful tummy critters keep our gut balanced (homeostasis) by battling unhelpful tummy critters — the exogenous, pathogenic bacteria. When the balance of the microbiome is disrupted, the result is dysbiosis.

The Consequences of Gut Dysbiosis

Here’s where this topic gets interesting.

Dysbiosis, just so we’re clear, refers to an imbalance in gut bacteria.

If you ask most of us what would happen when our gut bacteria gets out of balance, we’d probably say something like, “Well, maybe we’d be nauseous and get a stomachache. Or maybe we’d have problems like diarrhea or constipation.” And we’d be right: those are consequences of gut dysbiosis.

That’s not all that happens, though. Recent research shows that gut dysbiosis can have a significant impact on our brains and our behavior. The exact mechanisms are not known, but the effects are distinct and measurable.

In a laboratory setting in the rodent model (lab rats), evidence shows that gut dysbiosis:

· Promotes increased levels of the stress hormone cortisol

· Increases behaviors associated with anxiety

· Increases behaviors associated with depression

Here’s a quick reality check on the relationship between lab studies like these and humans: virtually every psychiatric medication we have for humans was developed with data obtained through the rodent model. That’s why researchers can extrapolate from this data about the effect of gut dysbiosis on human behavior. It’s not always a simple, “this happened in the lab, therefore this will happen in humans,” but it is an evidence-based paradigm with a proven history of providing valuable knowledge that applies to humans.

That’s why researchers now widely accept the idea that disruption in the gut microbiome has an impact on mood, emotions, and behavior, and may play a role in the development of psychiatric disorders. This recognition is the first step in connecting gut health to addiction: since anxiety and depression play a role in addiction, and gut health plays a role in anxiety and depression, it stands to reason that gut health may play a role in addiction.

Gut Dysbiosis and Addiction: The Connection

The connection just described is indirect: gut affects emotion, emotion affects addiction, therefore gut affects addiction — logical, but indirect, and so far, not conclusively proven with evidence. Now, with this new study, researchers are beginning to gather evidence that clarifies the role gut dysbiosis plays in alcohol and substance use disorders.

First, researchers sought to identify the presence or absence of gut dysbiosis in people with alcohol use disorder, cocaine use disorder, and non-specific substance use disorder. Here’s what they found:

· Alcohol Use Disorder:

o Approximately 31% of people with AUD have gut dysbiosis

o People with AUD displayed increased intestinal permeability, which contributes to gut dysbiosis

o People with AUD had elevated levels of two gut-derived chemicals related to depression (lipopolysaccharide and peptidoglycan).

· Cocaine Use Disorder:

o People with cocaine use disorder showed decreased levels of the bacteria Firmicutes.

o People with cocaine use disorder showed increased levels of the bacteria Bacteoriodetes.

· Substance Use Disorder:

o People with SUD had greater diversity in gut bacteria than people without SUD

o The diversity of gut bacteria in people with SUD increased relative to the duration of the SUD

o Three bacterial species were associated with SUD:

§ Thauera

§ Paracoccus

§ Prevotella

Collectively, the results of this study — and the studies it cites — show gut dysbiosis is common among people with alcohol use disorder, cocaine use disorder, and non-specific substance use disorder. In combination with discoveries related to how the gut microbiome affects general behavior and mood, as well as contributes to symptoms related to psychiatric disorders, this research opens up new avenues for treatment and support of people with alcohol and substance use disorder.

Implications for Therapeutics: The Gut-Brain Connection

To date, pharmacological treatments — i.e. medication — for opioid use disorder and alcohol use disorder prove effective for some patients, but not all. The research on the gut microbiome is directed toward the creation of what scientists call psychobiotics. Psychobiotics — which would include probiotics and prebiotics — are medications that can influence the gut-brain communication axis by “manipulating the composition of the gut microbiome or by manipulating its products via drugs designed to alter and exploit microbial metabolism.”

Initial evidence shows that psychobiotics have a positive effect on mood disorders such as depression and anxiety. Given the substantial rate of co-occurrence between AUD/SUD and these mood disorders, and the fact that both mood disorders and alcohol/substance use disorders are associated with impairments in the reward system of the human brain, scientists now hypothesize that pursuing the gut-brain connection may yield a new class of pharmacological therapeutics for addiction, in addition to the evidence-based medications already in use for alcohol use disorder and opioid use disorder.

This is good news for anyone in recovery, their families, and the mental health professionals who work in addiction. While some people in alcohol or substance use treatment achieve and maintain long-term sobriety, the fact of relapse remains. Any evidence-based tool that increases the chance of sustained sobriety — or perhaps prevents addiction before it manifests — will be a welcome addition to the therapeutic toolbox. Psychobiotics are not quite there yet, but this research holds promise and offers hope for the future — and anyone familiar with addiction knows that hope is a key component of successful, long-term recovery.



Christopher Johnston, MD, ABPM-ADM

Christopher Johnston, MD, ABPM-ADM, is the Chief Medical Officer for Pinnacle Treatment Centers and has practiced addiction medicine for the past 15 years