KORN KURATED RESEARCH

The Gut-Brain Link That Fuels Addictive Behaviors

Growing evidence suggests that gut microbiota is a key player in addiction, shaping behavior through the brain-gut axis. Disruptions in this delicate microbial balance can alter reward systems, immune responses, and neurochemical pathways, influencing addiction risk and recovery.

Addiction doesn’t arise in isolation. For many individuals, it follows years of emotional adversity, trauma, nutrient depletion, and gut dysfunction. People experiencing addiction often eat poorly or erratically, lack access to high-quality food, or struggle to digest nutrients efficiently. This triggers a cascade of bidirectional physiological effects—altered neurotransmitter signaling, inflammation, oxidative stress, and microbiome imbalance—that keep the addictive cycle in motion.

Dopamine deficiency is a core feature of all forms of addiction. This chemical imbalance alters how the brain perceives reward, making individuals more vulnerable to compulsive behaviors, substance dependence, and relapse. Serotonin also affects addictive behaviors. Ninety-five percent of the body’s serotonin is produced in the gut, not the brain. When the gut lining becomes inflamed or permeable, serotonin signaling falters. This disruption is linked to anxiety, depression, PTSD, and obsessive-compulsive behaviors—all of which frequently co-occur with addiction.

The research below affirms what our clinical experience demonstrates: addiction involves more than psychology or willpower—it has deep biological roots, especially in the gut.

Let’s break down some of the latest findings that will be useful for your clinical success.

The first study examines food addiction through the gut-brain-microbiome axis. Disruptions in this network affect both how the brain processes rewards and how the gut functions, setting the stage for addictive tendencies.

The second study uses genetic data to explore alcohol use disorder. Researchers found that people with higher levels of specific gut microbes—Eubacterium ventriosum and Porphyromonadaceae—appeared more resilient to alcohol abuse. These microbes influence neurotransmitter-related amino acids, which may help regulate cravings and behavior.

The third study also looks at food addiction, showing that individuals with this condition tend to have lower levels of Blautia wexlerae. When researchers reintroduced this microbe in mice—along with prebiotics that support its growth—the animals showed fewer compulsive eating behaviors. These findings suggest that gut-based interventions can help shift patterns of addictive eating.

The fourth study explores how opioid use disorder and gut health influence each other. As opioid use continues to rise worldwide, researchers are uncovering how these drugs affect the brain as well as the gut microbiome. This review highlights a two-way relationship: opioids disrupt the balance of gut microbes, damage the gut lining, and alter microbial function, while changes in the microbiome may, in turn, influence how the brain processes pain, reward, and addiction. 

The fifth study offers a broad review of how stress, addiction, and the microbiome are interconnected. It shows that gut health influences our ability to cope with stress and social challenges—both major risk factors for substance use disorders. The microbiome emerges here as a key player in emotional resilience.

The sixth and final study used mathematical modeling to understand how changes in the gut microbiome can impact addiction. The researchers found that when the microbiome is disrupted, it can shift toward a state that reinforces addictive behaviors. This creates a feedback loop that makes it harder for the body and brain to return to balance. Interestingly, the study also found that people with greater microbial diversity in their gut tend to be more resilient. In contrast, low diversity may make the system more vulnerable to dysbiosis and relapse. 

Tags: Addiction, Gut Microbiota, Gut Microbiome, Food Addiction, Alcohol Use Disorder, Opioid Use Disorder, Dysbiosis

Interested in Learning More?

• Course(s): Mental Health Disorders
• Course(s): Tapering Off Psychotropic Medications: Integrative and Naturopathic Strategies
• Book(s): Rhythms of Recovery
• Book(s): Nutrition Essentials For Mental Health

Referenced Research Publications

Nature reviews. Gastroenterology & hepatology
2020, November 17
DOI: 10.1038/s41575-020-0341-5

Brain-gut-microbiome interactions in obesity and food addiction

Abstract

Normal eating behaviour is coordinated by the tightly regulated balance between intestinal and extra-intestinal homeostatic and hedonic mechanisms. By contrast, food addiction is a complex, maladaptive eating behaviour that reflects alterations in brain-gut-microbiome (BGM) interactions and a shift of this balance towards hedonic mechanisms. Each component of the BGM axis has been implicated in the development of food addiction, with both brain to gut and gut to brain signalling playing a role. Early-life influences can prime the infant gut microbiome and brain for food addiction, which might be further reinforced by increased antibiotic usage and dietary patterns throughout adulthood. The ubiquitous availability and marketing of inexpensive, highly palatable and calorie-dense food can further shift this balance towards hedonic eating through both central (disruptions in dopaminergic signalling) and intestinal (vagal afferent function, metabolic endotoxaemia, systemic immune activation, changes to gut microbiome and metabolome) mechanisms. In this Review, we propose a systems biology model of BGM interactions, which incorporates published reports on food addiction, and provides novel insights into treatment targets aimed at each level of the BGM axis.

Reference

Gupta, A., Osadchiy, V., & Mayer, E. A. (2020). Brain-gut-microbiome interactions in obesity and food addiction. Nature Reviews Gastroenterology & Hepatology, 17(11), 655–672.
https://doi.org/10.1038/s41575-020-0341-5

Journal of molecular neuroscience : MN
2024, August 26
DOI: 10.1007/s12031-024-02259-7

Associations Between Gut Microbiota and Alcohol Abuse: A Mendelian Randomisation and Bioinformatics Study

Abstract

Alcohol abuse, also known as Alcohol Use Disorder (AUD), is a substance dependency psychiatric disorder. We aimed to establish a causal relationship between specific gut microbiota and alcohol abuse using Mendelian Randomisation (MR) and bioinformatics methods. We acquired summary data of genome-wide association studies (GWAS) for gut microbiota and alcohol abuse from the Mibiogen and Finngen databases, respectively. We conducted MR analyses using various methodologies and mapped the single nucleotide polymorphisms (SNPs) to genes via the FUMA GWAS platform. We further performed multiple enrichment analyses and a Multi-variable Mendelian Randomisation (MVMR) approach to examine whether gut microbiota influences alcohol abuse by modulating neurotransmitter-related amino acids. The MR analysis revealed an inverse relationship between the genus Eubacterium ventriosum group and the Porphyromonadaceae family with alcohol abuse. Gene enrichment analysis showed that these genes are expressed in brain tissue and are involved in addictive disorders, psychiatric conditions, immunological processes, neurotransmitter synthesis and synaptic regulation. MVMR analysis suggested that the Porphyromonadaceae family as well as genus Eubacterium ventriosum group may suppress alcohol abuse through the metabolism of neurotransmitter-related amino acids, especially Tryptophan. The MR analysis and bioinformatics investigations indicate that the genus Eubacterium ventriosum group and Porphyromonadaceae family confer a protective effect against alcohol abuse, potentially through the modulation of synaptic function.

Keywords: Alcohol abuse; Bioinformatics; Gut microbiota; Mendelian Randomisation; Neurotransmitter-related amino acids.

© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Reference

Wang, X., Pan, L., Gu, J., Gu, L., Lou, M., & Liu, Y. (2024). Associations Between Gut Microbiota and Alcohol Abuse: A Mendelian Randomisation and Bioinformatics Study. Journal of molecular neuroscience : MN, 74(3), 80. https://doi.org/10.1007/s12031-024-02259-7

Gut
2024, October 07
DOI: 10.1136/gutjnl-2023-331445

Gut microbiota signatures of vulnerability to food addiction in mice and humans

Abstract

Objective: Food addiction is a multifactorial disorder characterised by a loss of control over food intake that may promote obesity and alter gut microbiota composition. We have investigated the potential involvement of the gut microbiota in the mechanisms underlying food addiction.

Design: We used the Yale Food Addiction Scale (YFAS) 2.0 criteria to classify extreme food addiction in mouse and human subpopulations to identify gut microbiota signatures associated with vulnerability to this disorder.

Results: Both animal and human cohorts showed important similarities in the gut microbiota signatures linked to food addiction. The signatures suggested possible non-beneficial effects of bacteria belonging to the Proteobacteria phylum and potential protective effects of Actinobacteria against the development of food addiction in both cohorts of humans and mice. A decreased relative abundance of the species Blautia wexlerae was observed in addicted humans and of Blautia genus in addicted mice. Administration of the non-digestible carbohydrates, lactulose and rhamnose, known to favour Blautia growth, led to increased relative abundance of Blautia in mice faeces in parallel with dramatic improvements in food addiction. A similar improvement was revealed after oral administration of Blautia wexlerae as a beneficial microbe.

Conclusion: By understanding the crosstalk between this behavioural alteration and gut microbiota, these findings constitute a step forward to future treatments for food addiction and related eating disorders.

Keywords: NEUROPHARMACOLOGY; NUTRITION; OBESITY; PSYCHOLOGY.

© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Reference

Samulėnaitė, S., García-Blanco, A., Mayneris-Perxachs, J., Domingo-Rodríguez, L., Cabana-Domínguez, J., Fernàndez-Castillo, N., Gago-García, E., Pineda-Cirera, L., Burokas, A., Espinosa-Carrasco, J., Arboleya, S., Latorre, J., Stanton, C., Hosomi, K., Kunisawa, J., Cormand, B., Fernández-Real, J. M., Maldonado, R., & Martín-García, E. (2024). Gut microbiota signatures of vulnerability to food addiction in mice and humans. Gut, 73(11), 1799–1815. https://doi.org/10.1136/gutjnl-2023-331445

Microbial biotechnology
2024, October 17
DOI: 10.1111/1751-7915.70030

Understanding the impact of the gut microbiome on opioid use disorder: Pathways, mechanisms, and treatment insights

Abstract

The widespread use of opioids for chronic pain management not only poses a significant public health issue but also contributes to the risk of tolerance, dependence, and addiction, leading to opioid use disorder (OUD), which affects millions globally each year. Recent research has highlighted a potential bidirectional relationship between the gut microbiome and OUD. This emerging perspective is critical, especially as the opioid epidemic intensifies, emphasizing the need to investigate how OUD may alter gut microbiome dynamics and vice versa. Understanding these interactions could reveal new insights into the mechanisms of addiction and tolerance, as well as provide novel approaches for managing and potentially mitigating OUD impacts. This comprehensive review explores the intricate bidirectional link through the gut-brain axis, focusing on how opiates influence microbial composition, functional changes, and gut mucosal integrity. By synthesizing current findings, the review aims to inspire new strategies to combat the opioid crisis and leverage microbiome-centred interventions for preventing and treating OUD.

© 2024 The Author(s). Microbial Biotechnology published by John Wiley & Sons Ltd.

Reference

Kazemian, N., & Pakpour, S. (2024). Understanding the impact of the gut microbiome on opioid use disorder: Pathways, mechanisms, and treatment insights. Microbial biotechnology, 17(10), e70030. https://doi.org/10.1111/1751-7915.70030

Neurobiology of stress
2024, March 18
DOI: 10.1016/j.ynstr.2024.100629

A gut (microbiome) feeling about addiction: Interactions with stress and social systems

Abstract

In recent years, an increasing attention has given to the intricate and diverse connection of microorganisms residing in our gut and their impact on brain health and central nervous system disease. There has been a shift in mindset to understand that drug addiction is not merely a condition that affects the brain, it is now being recognized as a disorder that also involves external factors such as the intestinal microbiota, which could influence vulnerability and the development of addictive behaviors. Furthermore, stress and social interactions, which are closely linked to the intestinal microbiota, are powerful modulators of addiction. This review delves into the mechanisms through which the microbiota-stress-immune axis may shape drug addiction and social behaviors. This work integrates preclinical and clinical evidence that demonstrate the bidirectional communication between stress, social behaviors, substance use disorders and the gut microbiota, suggesting that gut microbes might modulate social stress having a significance in drug addiction.

Keywords: Drug addiction; Microbiota; Social behavior; Stress.

© 2024 The Authors.

Reference

García-Cabrerizo, R., & Cryan, J. F. (2024). A gut (microbiome) feeling about addiction: Interactions with stress and social systems. Neurobiology of stress, 30, 100629. https://doi.org/10.1016/j.ynstr.2024.100629

Communications biology
2023, July 26
DOI: 10.1038/s42003-023-05099-0

Evolutionary modeling suggests that addictions may be driven by competition-induced microbiome dysbiosis

Abstract

Recent studies revealed mechanisms by which the microbiome affects its host’s brain, behavior and wellbeing, and that dysbiosis – persistent microbiome-imbalance – is associated with the onset and progress of various chronic diseases, including addictive behaviors. Yet, understanding of the ecological and evolutionary processes that shape the host-microbiome ecosystem and affect the host state, is still limited. Here we propose that competition dynamics within the microbiome, associated with host-microbiome mutual regulation, may promote dysbiosis and aggravate addictive behaviors. We construct a mathematical framework, modeling the dynamics of the host-microbiome ecosystem in response to alterations. We find that when this ecosystem is exposed to substantial perturbations, the microbiome may shift towards a composition that reinforces the new host state. Such a positive feedback loop augments post-perturbation imbalances, hindering attempts to return to the initial equilibrium, promoting relapse episodes and prolonging addictions. We show that the initial microbiome composition is a key factor: a diverse microbiome enhances the ecosystem’s resilience, whereas lower microbiome diversity is more prone to lead to dysbiosis, exacerbating addictions. This framework provides evolutionary and ecological perspectives on host-microbiome interactions and their implications for host behavior and health, while offering verifiable predictions with potential relevance to clinical treatments.

Subject terms: Evolutionary theory, Microbial ecology, Computational models

Reference

Lewin-Epstein, O., Jaques, Y., Feldman, M. W., Kaufer, D., & Hadany, L. (2023). Evolutionary modeling suggests that addictions may be driven by competition-induced microbiome dysbiosis. Communications biology, 6(1), 782. https://doi.org/10.1038/s42003-023-05099-0