AddiBugs

• Overall objective:

Excessive and chronic alcohol consumption remains a major public health problem. In France alone, alcohol is responsible for 41,000 deaths a year, promotes more than 200 diseases including certain cancers, is the leading cause of hospitalization and generates a social cost of more than 100 billion euros/year. Although some treatments are available, their efficacy remains moderate or even low, and their side effects are not negligible. In addition, a large number of patients do not respond to these treatments, and a high relapse rate is observed, ranging from 40% to 60% within a year of stopping treatment.

To develop new treatments, AddiBugs aims to identify the unique microbial profile associated with alcohol use disorders, understand its effects, and determine how to modify it to alleviate symptoms. These symptoms are (1) loss of control over alcohol consumption, i.e. drinking more and more; (2) compulsive use, i.e. despite its known harmful effects (hangover, accident, illness, etc.), taking precedence over daily activities; (3) anxiety disorder, which is linked to craving, and contributes to relapse; (4) the irrepressible urge to consume alcohol, known as craving.

• Scientific and societal issues:

The scientific challenges are 1) to characterize the microbiome, from microorganisms to the molecules they produce, in the different symptoms of alcohol addiction in a cohort of patients in order to establish a signature of this microbiome linked to the symptoms 2) to demonstrate the causal role of this microbiome using robust pre-clinical models mimicking the different symptoms of alcohol addiction 3) to demonstrate that the gut-brain axis via the microbiome plays a role in the symptoms of alcohol addiction 4) unravel the molecular mechanisms by which this microbiome participates in the damage to the central nervous system involved in the various symptoms.

The societal challenges will be to propose new therapeutic approaches based on modulation of the intestinal microbiota with pre- or probiotic interventions to improve patient management, with a particular focus on relapse prevention.

• Project focuses:

The AddiBugs project focuses on:

1) Establish a microbiome signature in patients for the different symptoms associated with alcohol misuse.

2) Establish the causal role of the microbiome in alcohol addiction symptoms in robust pre-clinical models mimicking each of these symptoms.

3) Identify the role of the gut-brain axis in alcohol addiction

4) Identify molecular mechanisms by which this microbiome induces neuronal dysfunction in the central nervous system

• AddiBugs project presentation video