Emerging evidence indicates that the gut microbiome contributes to our ability to extract energy from the diet and influences development and function of the immune, endocrine and nervous systems, which regulate energy balance and behaviour. This has led to hypothesize that developing microbiome-based dietary interventions can be cost-effective measures to prevent diet-related and behavioural disorders. Yet this approach is restricted in practice by a lack of understanding of the specific species that contribute to these disorders and their interactions with host and lifestyle determinants. To progress beyond the state of the art, the MyNewGut proposal aims to: (1) shed light on the contribution of the human microbiome to nutrient metabolism and energy expenditure; (2) identify microbiome-related features that contribute to or predict obesity and associated disorders in human epidemiological studies; (3) understand how the microbiome is influenced by environmental factors and its role in brain and immune development and function in humans; and (4) provide proof-of-concept of the disease risk-reduction potential of dietary intervention with new foods/ingredients targeting the gut microbiome in humans. To this end, a translational multidisciplinary research strategy will be developed, combining experts in omic-technologies and all other scientific disciplines required. Consequently, the MyNewGut proposal will contribute to developing new approaches to prevent diet-related diseases (metabolic syndrome and obesity) and behavioural disorders through lifestyle changes, intake of pro- and prebiotics and semi-personalised and innovative food products. This will ultimately contribute to increasing the competitiveness of the European food industry and provide consumers with reliable claims on foods. Results will also help inform new strategies on public health, support EU legislation and improve the position of the EU in the field of food-related disease prevention.