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2023 CANTAB Research Grant: The microbiota-gut-brain axis in young binge drinkers: The interplay between alcohol use, microbiota composition and neurocognitive functioning
I am deeply grateful to Cambridge Cognition for awarding me the CANTAB Research Grant 2023 Secondary Award. Initiatives such as these are very important for researchers, as they rarely lack the motivation but very often lack the funding to develop their research projects.
I obtained my PhD in Neuroscience from the University of Santiago de Compostela, University of A Coruña and University of Vigo (Spain) in 2014. My research activities were focused on the study of brain activity associated with several cognitive processes (e.g., attention, working memory, inhibitory control) in college students who have a binge drinking pattern of alcohol consumption. After my PhD, I continued my journey as a postdoctoral fellow at the University of Minho (UMinho; Portugal). Since then, I progressed to the position of Assistant Researcher at the UMinho, at the Psychological Neuroscience Laboratory of the Center for Research in Psychology (CIPsi).
At present, my main area of interest is the study of the neurocognitive consequences of alcohol abuse and binge drinking in adolescents and young adults, as assessed by both electroencephalography (EEG) and structural/functional magnetic resonance imaging (MRI). I’m also interested in using cognitive training and neuromodulation as a potential strategy to modify (i.e., reduce) alcohol consumption habits.
What is the project about, and why is this important?
Adolescence and youth are periods of both vulnerability and opportunity in which many psychiatric disorders such as anxiety, depression or substance abuse manifest for the first time (Hawkins, 2009; Paus et al., 2008). In addition, significant maturational changes take place during this crucial developmental period, which is considered to last up to 24 years of age (Sawyer et al., 2018). The ongoing neuromaturation seems to involve greater vulnerability –in comparison to adulthood- to disruptive events in the brain such as binge drinking (BD) (Chung et al., 2018; Spear, 2016). Indeed, this prevalent pattern of consumption –characterized by repeated alcohol intoxications- is of special concern, as it has been associated with structural and functional impairments in still-maturing regions (e.g., the prefrontal cortex) (Cservenka & Brumback, 2017; Pérez-García et al., 2022) and neuropsychological and neurofunctional deficits in executive functions (e.g. ,inhibitory control) (Almeida-Antunes et al., 2021; Carbia et al., 2018) together with a high risk of developing future alcohol addiction (Crews et al., 2016; Tavolacci et al., 2019).
We are beginning to understand that external influences such alcohol are impacting not only the brain and other key organs but also our microbiota population (the collection of trillions of microorganisms that inhabit the human body), especially the bacteria residing in our gut (i.e., the gut microbiota) (Carbia et al., 2021; Leclerq et al., 2017). In the last decade, research has reaffirmed the idea of a microbiota-gut-brain axis of bi-directional communication through neural, immune and endocrine pathways (Cryan and Dinan, 2012; Morais et al.., 2021). Alterations in the microbiota in relation to the pathophysiology of mood disorders, stress response, and –more recently- alcohol abuse are increasingly being recognized as a novel paradigm in neuroscience (Angoa-Perez & Kuhn, 2021; Cryan et al., 2020).
Accordingly, preclinical studies indicate that alcohol misuse disrupts the gut microbiota and that these alterations are linked to changes in brain and behavior, including increased craving, impulsivity and compulsive alcohol seeking –suggesting a potential role for microbiota in loss of control over drinking (Jadhav et al., 2018; Segovia-Rodríguez et al., 2022). Recent studies have reported that alcohol-induced microbiota alterations may stimulate the release of proinflammatory cytokines, which ultimately can reach the brain and alter its normal functioning (Temko et al., 2017). Similarly, accumulating evidence has shown that BD cause elevation of peripheral cytokines, which appears to promote neuroinflammation and contribute to neurocognitive deficits (Pascual et al., 2018). Despite this inflammatory cascade being compatible with alterations in the gut-brain system, no study to date has investigated the effects of BD on the microbiota-gut-brain axis.
In addition, recent research has shown that interventions with psychobiotics -dietary supplementations with mental health benefits (Dinan et al., 2013)- lead to reductions in alcohol-induced proinflammatory cytokines (Bajaj et al., 2021; Leclerq et al., 2017) as well as to changes in cognition and brain activation patterns (Bagga et al., 2018; Rode et al., 2022). Accordingly, targeting the gut microbiota in youths with a BD pattern could eventually decrease its neurotoxic effects, a totally unexplored research field with major clinical applications.
What are you hoping to discover?
In the present project, we will investigate for the first time the interplay between the Brain (neurocognitive profile), the Bug (gut microbiome) ant the Binge (BD-induced damage) and we will go beyond these three Bs by examining the therapeutic potential of gut microbiota-targeted interventions on behavioral, psychological, immune and neurocognitive responses in adolescents and youths with a BD pattern.
For this purpose, the main objectives of the project will be: O1) [Binge&Bugs] to evaluate whether a BD pattern of alcohol consumption may induce gut microbiota dysbiosis in young Portuguese college students; O2) [Bugs&Brain] to determine whether the alcohol-induced altered microbial profile is associated with neuropsychological, neurostructural and/or neurofunctional impairments in young BDs; O3) [Bugs&Brain&Binge] to examine whether administration of psychobiotics in young BDs improves the composition of the gut microbiota and, consequently, reduces the alcohol-induced cognitive/brain anomalies.
Which CANTAB™ tests will you use?
Despite alterations in several cognitive processes associated with BD have already been demonstrated, no study so far has explored the potential relationship between gut dysbiosis and cognitive deficits in young BDs. To this end, control and BD groups will undergo a neuropsychological assessment by the CANTAB battery aiming at evaluating multiple cognitive domains –frequently impaired in individuals with alcohol misuse- including: emotional processing (Emotional Recognition Task), memory skills (Spatial Working Memory and Delayed Matching to Sample tasks), cognitive flexibility (Intra-Extra Dimensional Set Shift), inhibitory control (Stop Signal Task), and decision making (Cambridge Gambling Task). The neuropsychological approach using the CANTAB battery will be crucial in this project, as it is expected to bring new knowledge on the BD-induced early perturbations as well as on the potential triadic relationship between alcohol, cognitive functioning and gut microbiota during such a critical developmental period as adolescence and young adulthood.
How important was funding from Cambridge Cognition for your work?
Cambridge Cognition’s support will help us to determine which cognitive processes are most affected by BD. As a next step, we would like to explore whether the BD-induced cognitive deficits (assessed by the CANTAB battery) are similar to those observed in alcohol-dependent patients, thus confirming the continuum hypothesis, i.e., that BD and alcohol abuse are two stages of the same phenomenon.
On the other hand, if intervention with psychobiotics is shown to be effective in reducing the neurotoxic effects of BD, the use of pre/probiotics would constitute a new way to treat the negative impact of alcohol on the brain. Therefore, further studies on the use of psychobiotics as a potential alcohol harm reduction strategy will be needed and we hope to be one of the research teams conducting that research.
Connect with CIPsi
Instagram: https://www.instagram.com/cipsi_uminho/
References
Almeida-Antunes, N., Crego, A., Carbia, C., Sousa, S. S., Rodrigues, R., Sampaio, A., & López-Caneda, E. (2021). Electroencephalographic signatures of the binge drinking pattern during adolescence and young adulthood: A PRISMA-driven systematic review. NeuroImage: Clinical, 29, 102537.
Angoa-Perez, M., & Kuhn, D. M. (2021). Evidence for modulation of substance use disorders by the gut microbiome: hidden in plain sight. Pharmacological reviews, 73(2), 571-596.
Bagga, D., Reichert, J. L., Koschutnig, K., Aigner, C. S., Holzer, P., Koskinen, K., … & Schöpf, V. (2018). Probiotics drive gut microbiome triggering emotional brain signatures. Gut Microbes, 9, 486-496.
Bajaj, J. S., Gavis, E. A., Fagan, A., Wade, J. B., Thacker, L. R., Fuchs, M., … & Gillevet, P. M. (2021). A randomized clinical trial of fecal microbiota transplant for alcohol use disorder. Hepatology, 73(5), 1688-1700.
Carbia, C., Lannoy, S., Maurage, P., López-Caneda, E., O’Riordan, K. J., Dinan, T. G., & Cryan, J. F. (2021). A biological framework for emotional dysregulation in alcohol misuse: from gut to brain. Molecular Psychiatry, 26(4), 1098-1118.
Carbia, C., López-Caneda, E., Corral, M., & Cadaveira, F. (2018). A systematic review of neuropsychological studies involving young binge drinkers. Neuroscience & Biobehavioral Reviews, 90, 332-349.
Chung, T., Creswell, K. G., Bachrach, R., Clark, D. B., & Martin, C. S. (2018). Adolescent binge drinking: Developmental context and opportunities for prevention. Alcohol research: current reviews, 39(1), 5-15.
Crews, F. T., Vetreno, R. P., Broadwater, M. A., & Robinson, D. L. (2016). Adolescent alcohol exposure persistently impacts adult neurobiology and behavior. Pharmacological reviews, 68(4), 1074-1109.
Cryan, J. F., & Dinan, T. G. (2012). Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nature Reviews Neuroscience, 13, 701-712.
Cryan, J. F., O’Riordan, K. J., Sandhu, K., Peterson, V., & Dinan, T.G. (2020). The gut microbiome in neurological disorders. Lancet Neurology, 19, 179–194.
Cservenka, A., & Brumback, T. (2017). The burden of binge and heavy drinking on the brain: effects on adolescent and young adult neural structure and function. Frontiers in psychology, 8, 1111.
Dinan, T. G., Stanton, C., & Cryan, J. F. (2013). Psychobiotics: a novel class of psychotropic. Biological Psychiatry, 74, 720-726.
Jadhav, K. S., Peterson, V. L., Halfon, O., Ahern, G., Fouhy, F., Stanton, C., Cryan J. F. & Boutrel, B. (2018). Gut microbiome correlates with altered striatal dopamine receptor expression in a model of compulsive alcohol seeking. Neuropharmacology, 141, 249-259.
Leclercq, S., de Timary, P., Delzenne, N. M., & Stärkel, P. (2017). The link between inflammation, bugs, the intestine and the brain in alcohol dependence. Translational Psychiatry, 7, e1048.
Morais, L. H., Schreiber IV, H. L., & Mazmanian, S. K. (2021). The gut microbiota–brain axis in behaviour and brain disorders. Nature Reviews Microbiology, 19(4), 241-255.
Pascual, M., Montesinos, J., & Guerri, C. (2018). Role of the innate immune system in the neuropathological consequences induced by adolescent binge drinking. Journal of Neuroscience Research, 96, 765-780.
Pérez-García, J. M., Suárez-Suárez, S., Doallo, S., & Cadaveira, F. (2022). Effects of binge drinking during adolescence and emerging adulthood on the brain: A systematic review of neuroimaging studies. Neuroscience & Biobehavioral Reviews, 137, 104637.
Rode, J., Edebol Carlman, H. M., König, J., Hutchinson, A. N., Thunberg, P., Persson, J., & Brummer, R. J. (2022). Multi-strain probiotic mixture affects brain morphology and resting state brain function in healthy subjects: an RCT. Cells, 11(18), 2922.
Segovia-Rodríguez, L., Echeverry-Alzate, V., Rincón-Pérez, I., Calleja-Conde, J., Bühler, K. M., Giné, E., … & López-Moreno, J. A. (2022). Gut microbiota and voluntary alcohol consumption. Translational Psychiatry, 12(1), 146.
Spear, L. P. (2016). Alcohol consumption in adolescence: a translational perspective. Current addiction reports, 3, 50-61.
Tavolacci, M. P., Berthon, Q., Cerasuolo, D., Dechelotte, P., Ladner, J., & Baguet, A. (2019). Does binge drinking between the age of 18 and 25 years predict alcohol dependence in adulthood? A retrospective case–control study in France. BMJ open, 9(5), e026375.
Temko, J. E., Bouhlal, S., Farokhnia, M., Lee, M. R., Cryan, J. F., & Leggio, L. (2017). The microbiota, the gut and the brain in eating and alcohol use disorders: a ‘Ménage à Trois’?. Alcohol and alcoholism, 52(4), 403-413.
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