Abstract Body

Polyunsaturated fatty acids (PUFAs) are essential fatty acids which are provided to the body through the diet. The brain is one of the richest organs in the body and has a high need in PUFAs. There are 2 main families of PUFAs, n-3 (or omega 3) and n-6 (or omega6). While it is quite easy to find n-6 PUFAs in westernized diets, the need in n-3 PUFAs is poorly reached, leading to decreased level of docosahexaenoic acid (DHA) in the brain.

In humans, poor levels of blood n-3 PUFAs and brain DHA are associated to a higher prevalence of cognitive disorders and depression. However, the mechanisms underlying the effect of DHA on brain functions are poorly understood. Using mice models of n-3 PUFAs dietary deficiency or supplementation, we revealed that in the brain, DHA regulate neuroinflammatory pathways, in particular through its effect on microglia, the main innate immune system cell in the brain. In addition, n-3 PUFAs are key actors of ndocannabinoid- dependent synaptic plasticity. While neuroinflammation and eCB-dependent synaptic plasticity are crucial to cognition and emotional behaviour alterations, our results bring to the clinical scene the importance of controlling dietary n-3 PUFAs to protect the brain from the adverse effect of stres or inflammation.

Altogether, our work brings a better comprehension of how dietary n-3 PUFAs participate to brain physiology and protect from the development of mood and cognitive disorders. It opens new avenues for the use of these lipids in the protection and treatment of brain diseases.

Abstract Body

Anorexia nervosa (AN) is one of the most common chronic disorders in adolescence with still high mortality rates. Knowledge on gut-brain interaction might help to develop new treatments, as severe starvation-induced changes of the microbiome in AN-patients have been demonstrated, which do not alleviate with weight gain. In our own pilot study alpha-diversity was increased in patients with AN after short-term weight recovery, while beta diversity showed clear group differences with healthy controls before and after weight gain. A reduction of taxa belonging to Enterobacteriaceae at admission and discharge and an increase in taxa belonging to Lachnospiraceae at discharge were typically found in patients with AN.

The work plan of our European project comprises an observational study and two phase II RCTs with the application of omega-3-PUFA and a multistrain psychobiotic to both, humans and rodents. With the help of a well-established animal model for AN (activity-based anorexia, ABA), the effect of stool transplants from patients to rodents will be analysed. Longitudinal MRI will be conducted in rodents together with cellular and molecular brain analyses. In addition, immune response and circulating antibodies associated with the presence of certain bacterial strains and interaction with hunger and satiety hormones will be explored. We hope that by this translational research we may systematically investigate the role of an altered microbiome for the course of AN and to identify new therapeutic tools.