Chronic diseases have increased to epidemic proportions in Western countries. The
composition of the gut microbiota influences health and disease. The comprehensive,
systems biology approach of the Human Functional Genomics Project (HFGP) offers
unprecedented opportunities to unravel to effects of gut microbiome on health and
disease. Still, important gaps in our knowledge remain of how diet influences the
composition of the microbiome and its effects on health. TransMic aims to fill these gaps
by studying the effects of traditional versus modern ‘Western’ diets on gut microbiome
and the functional consequences for health. Data from cohorts from populations in
different phases of the demographic transition from Tanzania (Work Package1), Burkina
Faso (WP2) and Europe will be used and analyzed using the comprehensive HFGP
approach (WP3). In addition, a short dietary intervention will be performed switching
young subjects from a Western to a traditional diet and vice versa (WP4). Omics-based
data, including microbiome composition, genetics, transcriptome, metabolome and
lipidome will be related to functional data, such as immune responses. This large-scale
analysis will provide important fundamental insights in the effects of diet on microbiome
and health in general and the health effects of ‘westernization’ of diet in particular. It will
thereby provide the necessary data for future innovative interventions to improve health,
such as directed dietary microbiota modulation.

The first part pf TransMic studied the effects of rural-urban transition and the nutrition transition on different important biological processes. We found that healthy, urban-living Tanzanian individuals have increased proinflammatory cytokine production compared to rural-living individuals, suggesting increased inflammation at the tissue level. We also identified different food-derived and endogenous metabolites underlying these differences in immune profiles. Abundant metabolites in rural-living Tanzanians were predominantly metabolites with anti-inflammatory properties derived from traditional food sources. In contrast, metabolites belonging to the bile acid and cholesterol metabolism were more abundant in urban-living individuals. The importance of these metabolites to modulate immune responses was further substantiated by showing that plasma from urban-living individuals induced long-term reprogramming of monocytes into a proinflammatory phenotype, which could be prevented by dietary constituents from the traditional diet.