In this project we will develop a novel system that allows scientific support for assessment of human health effects through microbiome modulation. In the food and supplements market there is a diversity of products that aim to provide health effects through modulation of the microbiome in the gut. Currently the measurement of health effects in relatively healthy subjects is difficult and no standardized methods for health assessment related to microbiome modulation exist. TNO has developed the PhenFlex technology that uses resilience of the human system as a measure of health, called phenotypic flexibility. This approach was primarily developed for assessment and improvement of metabolic health and disorders such as type 2 diabetes (T2D) and appeared to be successful1,2. Here we will apply the PhenFlex approach to investigate if we can relate microbiome (modulation) to the human health read-out. Microbiome modulations often have a relation to low grade inflammation, one of the biological processes important for the development of T2D. Here we explore the use of microbiome measurement technology combined with the PhenFlex technology to investigate health effects of selected microbiome modulating intervention. Microbiome modulation will be assessed by I-screen analysis (an in vitro platform which can be used to experimentally analyze the effects of compounds and ingredients on microbiome composition and functionality) and results of this functional analysis will be linked to human study data. The combination of microbiome modulation and PhenFlex technology is novel and can have a major impact on the sector, contributing to possible scientific substantiation of health effects from, nutritional interventions such as pro- and prebiotics, novel technology development related to food, and supplement product development for gut health, and later also for consumers and society.