A biological framework for emotional dysregulation in alcohol misuse: from gut to brain

Carbia, Carina; Lannoy, Séverine; Maurage, Pierre; López‐Caneda, Eduardo; O’Riordan, Kenneth J.; Dinan, Timothy G.; Cryan, John F.

doi:10.1038/s41380-020-00970-6

Cited by 53 publications

(66 citation statements)

References 231 publications

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“…More recently these authors have shown that gut microbiota induce changes in metabolism linked to alterations in sociability and depression in AUD (Leclercq et al, 2020). Recently, we have proposed a framework of how emotional dysregulation and alcohol-related microbiome dysbiosis could contribute to accelerate the addiction cycle in AUD (Carbia et al, 2020), highlighting the importance of integrating disparate aspects such as microbiota for advancing in the understanding of addiction.…”

Section: Implication For Substance Use Disordersmentioning

confidence: 99%

Microbiota‐gut‐brain axis as a regulator of reward processes

García-Cabrerizo

Carbia

Riordan

et al. 2021

Journal of Neurochemistry

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The reward system is a set of neuronal structures responsible for the processing of a number of psychological components, such as 'wanting', 'liking' and associative learning (Berridge & Robinson, 2003).These three processes occur together, 'wanting' dominates the initial appetitive phase, 'liking' dominates the consummatory phase, and learning occurs through the reward-behavioural cycle (Berridge et al., 2016). Both phenomena are underpinned by different brain circuits and neurotransmitter systems. The 'wanting' component is largely controlled by the dopaminergic system, whereas the 'liking' component is thought to be more mediated by opioid and GABAergic systems (Berridge & Robinson, 2003). The neural circuitry constituting the anatomical and neurochemical substrate for reward and pleasure was described several decades ago by Olds and Milner, who, after implanting electrodes in certain areas of the central nervous system (CNS) and administering electrical microstimuli, demonstrated a pleasure response in the animals (Olds and Milner 1954).Following this, it was proposed that the monoaminergic activity could underlie the neurochemical basis of pleasure, with the monoaminergic system playing an important role in drug reinforcement

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Section: Implication For Substance Use Disordersmentioning

confidence: 99%

Microbiota‐gut‐brain axis as a regulator of reward processes

García-Cabrerizo

Carbia

Riordan

et al. 2021

Journal of Neurochemistry

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“…Psychiatric disorders, such as depression, bipolar disorders, and anxiety disorders, preceded the onset of alcohol abuse, and chronic alcohol exposure induced anxiety and depression symptoms, further aggregating AUD. Alcohol-induced anxiety and depression can bidirectionally interact with gut microbiome (Carbia et al, 2021). As summarized in Table 3, a series of studies from the same research group showed that only part of the alcohol-dependent patients showed dysbiosis in gut microbiome, while the dysbiosis-induced gut leakiness was highly correlated with alcohol craving, alcohol-induced depression, anxiety, and possibility of relapse.…”

Section: The Role Of the Microbiome-gut-brain Axis In Alcohol-induced Anxiety And Depressionmentioning

confidence: 99%

“…These products can be released to the systemic circulation such as blood stream and then transported to the brain, and these gut derived components also target the HPA axis and vagus nerve. These all together further impact on brain barrier integrity and immunoactivities in brains and alter the reward system (Carbia et al, 2021;Garcia-Cabrerizo et al, 2021). Second, the gut microbiome plays an important role in the cycle of development and maintenance of addiction.…”

Section: Confounding Factors Complicate the Problemmentioning

confidence: 99%

“…Repeated binge induces the progressively microbiome imbalances and contributes to early emotional dysregulation, and further motivates the craving and drug seeking behaviors. At the withdrawal/negative effect stage, exaggerated emotional disturbances and dysbiosis combine with the negative effects related to withdrawal driven negative reinforcement and finally accelerate the transition to compulsive alcohol use (Wise and Koob, 2014;Carbia et al, 2021;Garcia-Cabrerizo et al, 2021). Additionally, the substance-related mental disorders, especially depression and anxiety, could further exacerbate dysbiosis (Reyes et al, 2020;Carbia et al, 2021).…”

Section: Confounding Factors Complicate the Problemmentioning

confidence: 99%

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The Microbiome–Gut–Brain Axis, a Potential Therapeutic Target for Substance-Related Disorders

Chen

Cai

et al. 2021

Front. Microbiol.

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Substance addiction is a complex worldwide public health problem. It endangers both personal life and social stability, causing great loss on economy. Substance-related disorder is considered to be a complicated chronic brain disorder. It resulted from interactions among pharmacological properties of addictive substances, individual susceptibility, and social–environmental factors. Unfortunately, there is still no ideal treatment for this disorder. Recent lines of evidence suggest that gut microbiome may play an important role in the pathogenesis of neuropsychiatric disorders, including substance-related disorders. This review summarizes the research on the relationship between gut microbiome and substance-related disorders, including different types of substance, different individual susceptibility, and the occurrence and development of substance-induced mental disorders. We also discuss the potentiation of gut microbiome in the treatment of substance-related disorders, especially in the treatment of substance-induced mental disorders and manipulation on individuals’ responsiveness to addictive substances.

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“…Thus, alcohol-induced changes in the gut microbiota may contribute not only to development of alcoholic liver disease, but also to a variety of CNS disorders (Engen et al 2015 ; García-Cabrerizo et al 2021 ). Indeed, it has been suggested that use of probiotic might be of potential use in prevention and treatment of alcohol-associated pathologies (Engen et al 2015 ; Lowe et al 2018 ; Rodriguez-Gonzalez and Orio 2020 ; Carbia et al 2021 ; Gupta et al 2021 ). In this regard, it was recently reported that butyrate (BUT) ameliorates alcoholic fatty liver disease in mice (Zhang et al 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Sodium Butyrate Protects Against Ethanol-Induced Toxicity in SH-SY5Y Cell Line

et al. 2021

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Alcohol use disorder (AUD), brought about by excessive alcohol use, is associated with damages to several organs including the brain. Chronic excessive use of alcohol can compromise intestinal integrity, leading to changes in gut microbiota (GM) composition known as dysbiosis. Dysbiosis, by disruption of the gut-brain axis (GBA), further exacerbates the deleterious effects of alcohol. One of the fermentation by-products of GM is butyrate (BUT), a short-chain fatty acid (SCFA) that plays an important role in maintaining homeostasis of the GBA. Alcohol metabolism results in formation of acetaldehyde, a highly reactive compound that reacts with dopamine in the brain to form toxic adducts such as salsolinol. Recent studies indicate potential neuro-protective effects of BUT against various toxicants including salsolinol. Here, we sought to investigate whether BUT can also protect against alcohol toxicity. Pretreatment of neuroblastoma-derived SH-SY5Y cells with 500 mM ethanol (ETOH) for 24 h resulted in approximately 40% reduction in cell viability, which was totally blocked by 10 µM of either BUT or AR 420,626 (AR), a selective fatty acid 3 receptor (FA3R) agonist. The neuro-protective effects of both BUT and AR were significantly (80%) attenuated by beta-hydroxy butyrate (BHB), a selective FA3R antagonist. Interestingly, combination of BUT and AR resulted in synergistic protection against ETOH, which was totally blocked by BHB. These findings suggest potential utility of butyrate and/or FA3R agonists against ETOH-induced toxicity.

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A biological framework for emotional dysregulation in alcohol misuse: from gut to brain

Cited by 53 publications

References 231 publications

Microbiota‐gut‐brain axis as a regulator of reward processes

Microbiota‐gut‐brain axis as a regulator of reward processes

The Microbiome–Gut–Brain Axis, a Potential Therapeutic Target for Substance-Related Disorders

Sodium Butyrate Protects Against Ethanol-Induced Toxicity in SH-SY5Y Cell Line

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