Alcohol use disorder (AUD) has been associated with impairments in social and emotional cognition that play a crucial role in the development and maintenance of addiction. Repeated alcohol intoxications trigger inflammatory processes and sensitise the immune system. In addition, emerging data point to perturbations in the gut microbiome as a key regulator of the inflammatory cascade in AUD. Inflammation and social cognition are potent modulators of one another. At the same time, accumulating evidence implicates the gut microbiome in shaping emotional and social cognition, suggesting the possibility of a common underlying loop of crucial importance for addiction. Here we propose an integrative microbiome neuro-immuno-affective framework of how emotional dysregulation and alcohol-related microbiome dysbiosis could accelerate the cycle of addiction. We outline the overlapping effects of chronic alcohol use, inflammation and microbiome alterations on the fronto-limbic circuitry as a convergence hub for emotional dysregulation. We discuss the interdependent relationship of social cognition, immunity and the microbiome in relation to alcohol misuse- from binge drinking to addiction. In addition, we emphasise adolescence as a sensitive period for the confluence of alcohol harmful effects and emotional dysregulation in the developing gut-brain axis.

CC has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No. 754535. SL has received support from the Belgian American Educational Foundation. PM (Senior Research Associate) is funded by the Belgian Fund for Scientific Research (F.R.S.-FNRS, Brussels, Belgium). EL-C was supported by the Portuguese Foundation for Science and Technology (FCT), within the scope of the Individual Call to Scientific Employment Stimulus (CEECIND/02979/2018).