About
Adolescence and young adulthood are periods of both vulnerability and opportunity in which many psychiatric disorders such as anxiety, depression or substance abuse manifest for the first time. In addition, significant maturational changes take place during this crucial developmental period, which is considered to last up to 24 years of age. The ongoing neuromaturation seems to involve greater vulnerability –in comparison to adulthood- to disruptive events in the brain such as binge drinking (BD). 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) and neuropsychological/neurofunctional deficits in executive functions (e.g. inhibitory control [IC]) together with a high risk of developing future alcohol addiction.
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 [GM]). The last decade has reaffirmed the idea of a microbiota-gut-brain axis of bi-directional communication through neural, immune and endocrine pathways. Alterations in the microbiota in relation to the pathophysiology of mood disorders, stress response, and –more recently- alcohol abuse are increasingly being recognized and viewed as a novel paradigm in neuroscience.
Accordingly, recent preclinical studies indicate that alcohol misuse disrupts the GM 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. 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. Similarly, accumulating evidence has shown that BD cause elevation of peripheral cytokines, which appears to promote neuroinflammation and contribute to neurocognitive deficits. 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) lead to reductions in alcohol-induced proinflammatory cytokines as well as to improvements in cognition and brain activation patterns. 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.
In the present project, we will pioneer the field by investigating 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 project will implement a multidisciplinary approach involving a pre-intervention assessment of the three Bs. We will focus on 1) craving and inhibitory processes that play a central role in the cycle of addiction (Brain); 2) composition and function of major bacterial populations (Bugs); and 3) how these features are related to alcohol drinking behavior (Binge). These core variables will be re-assessed after the intervention protocol, a randomized and placebo-controlled design aiming at determining whether psychobiotics administration targeting the gut microbiome is able to restore gut functioning, attenuate inflammation and reduce neurocognitive anomalies resulting from repeated BD episodes (which would constitute an entirely new form of treatment of alcohol-related damage).
