Exploring the association of gut-brain axis with cognitive and behavioural aspects of alcohol use disorder

There has been an emerging interest in understanding the neurobiological and behavioural components of alcohol addiction pertaining the role of gut brain axis. Motivation, salience, craving for the addictive substance and the negative emotional state ridden relapses are important behavioural aspects in continuing the addiction trajectory. Although a number of molecules as anti -craving agents have been tried in alcohol dependence; they largely target the neurochemical milieu of reward pathway in brain. However, the response to these molecules is not uniform, neither long lasting. Hence exploring the missing link of gut brain axis in pro addictive cognitions and behaviour is important. Addictive disorders esp. alcohol dependence is linked with neuropsychological deficits viz. visuospatial processing, attention, memory, executive functioning esp. impaired set shifting, response inhibition, poor decision making, planning and organising. known to perpetuate the cycle of addiction and relapses. In various preclinical and few human studies, chronic alcohol consumption has been shown to cause alteration in the gut microbial flora and changes in the gut luminal barrier. The resident bacterial products especially endotoxins (especially lipopolysaccharide), of certain specific gut bacteria might have a role in triggering brain inflammatory processes either via hepatic circulation or through the vague nerve. This in turn can modulate various cognitive, emotional and behavioural aspects of addictive disorders. Restoring the altered gut microbiome constitution via (pre/probiotic) towards a healthy state might remodulate the gut brain dysbiosis and resulting neuron-inflammation. These agents are either This could indirectly impact the altered cognitive and emotional processes in context of alcohol addiction. In this regard, introducing Probiotics and prebiotics is one way of facilitating healthy gut microbiome. these are either live bacterial stains or nondigestible carbohydrates which facilitate healthy microbiome in the gut respectively. Prebiotics are essentially the non-digestible carbohydrates; resistant to alpha amylase, facilitate healthy gut bacteria and produce fermentation products viz. short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate. Butyrate has a role in cell proliferation via gene regulation and epigenetic mechanism. Interventions involving gut microbiome alteration using pre or probiotics has been done in alcoholic and non-alcoholic liver conditions. However, studies exploring its role in addictive behaviours are still in early stages. High Amylose maize Starch (HAMS) meets the criteria for safety, durability, and availability as a dietary intervention for gut inflammation in pre-existing clinical research. However, the role of prebiotics has not been widely studied in its effect in altering behavioural aspects of alcohol addiction via the similar gut microbiota altering processes. Hence our study will attempt to explore the role of high amylose maize starch as a prebiotic agent in facilitating the healthy gut microbiota and altering the behavioural aspects of addiction esp. craving and motivation in subjects with alcohol use disorder along with the conventional antic raving medications and psychological therapies. The symptoms of alcohol tolerance and withdrawal, with uncontrolled intake and craving, are the core symptoms of alcohol addiction, indicating neurologic adaptation or so-called physiologic dependence. Personality traits esp. impulsivity (attentional, motor, and non-planning impulsiveness) make susceptible individuals more prone to seek substance associated positive emotional state. (Coskunpinar A, Dir AL, Cyders MA. 2013.) Multidimensionality in impulsivity and alcohol use: a meta-analysis using the UPPS model of impulsivity. The severity of alcohol addiction is correlated with the intensity of their craving, cognitive dysfunction, anxiety, and depressive symptoms. As we mentioned above, systemic inflammation may play an important role in the development of alcohol addiction; gut barrier dysfunction and inflammation in both the gut and liver may contribute to peripheral inflammation and cause brain inflammation , inducing inflammation of brain cells such as microglia or astrocytes . The sickness behaviour theory may link systemic inflammation to both alcohol addiction and mood disorders . This theory supports that peripheral inflammation, such as leaky gut, activates the immune system and produces cytokines that can reach the brain, causing fever, fatigue, lassitude, inability to concentrate, and withdrawal from social interactions; when the above behaviours persist, depressive symptoms may develop . Though studies support alcohol addiction or craving is associated with systemic inflammation, the causality is still unclear. Nevertheless, the combination of alcohol craving and negative emotions such as anxiety and depression are highly associated with drug-seeking behaviours and relapse, indicating that reducing systemic inflammation may improve psychological well-being and prevent relapse.