Background: Current dietary and public health recommendations addressing obesity do not as yet include recommendations pertaining to the gut microbiome. As a corollary, no microbiome-related health claims made on foods have as yet been proposed. Scope: The MyNewGut project aims, amongst others, to provide guidance for the establishment of dietary and public health recommendations related to the role microbiome in the onset and development of obesity. Moreover, the project's forthcomings should allow the compilation of a guidance document for microbiome-related health claims. Key findings: Of all the physiological effects resulting from changes in the microbiome, insulin resistance is the most direct diet-modifiable parameter related to obesity. Improving insulin resistance is considered to be the key health benefit conferred by the targeted modulation of the gut microbiome, through the development and application of foods containing microbiome-targeted fibers and micro-organisms. Conclusions: In order to facilitate guidance for the development of public health and dietary recommendations, as well as for health claim substantiation related to the gut microbiome, foods containing microbiome-targeting dietary fibers and microorganisms will be developed and studies with these foods should provide for the total body of clinical evidence specifically addressing the central theme of ‘insulin resistance’ in obesity, still leaving ample room for the inclusion of other parameters of interest. The latter is pivotal since an impact of other parameters on obesity should be addressed as well, particularly in view of the multifaceted modes of action of the microbiome.