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Integrated nutrigenomic and metabolomic analysis of Africans with variable diet

ABSTRACT: Untargeted metabolic profiling and lipidomics profiling will be used to characterize a broad array of metabolites from plasma in 450 ethnically diverse individuals from Ethiopia, Tanzania, and Botswana with diverse diets. Mass spectrometry will be used to quantify metabolites previously found to be associated with cardiometabolic risk as well as the most informative metabolites from the untargeted screen. We will test for association of selected biomarkers with diet, geography, ancestry, and phenotypic variation. Metabolites obtained will be correlated with diet as well as clinical and anthropometric phenotypes. Using existing tools, we will assemble metabolites that associate with the various phenotypes into pathways and larger networks to provide insights into factors that relate to cardiometabolic health and disease. Finally, we will integrate metabolic and phenotypic data with genetic data from the SNP array and with high coverage whole genome sequence data. We will identify loci that play a role in local adaptation to diverse diets and will identify genetic variants associated with metabolite levels (mQTLs) and with the phenotypic traits listed above.

ORGANISM(S): Human Homo Sapiens

TISSUE(S): Blood

DISEASE(S): Heart Disease

SUBMITTER: Maureen Kachman

PROVIDER: ST000818 | MetabolomicsWorkbench | Thu Jul 13 00:00:00 BST 2017

REPOSITORIES: MetabolomicsWorkbench

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Project description:Genetic and molecular evidence to support the hypothesis that fungal secondary metabolites play a significant role in protecting the fungi against fungivory is scarce. We investigated the impact of fungal secondary metabolites on transcript regulation of stress related expressed sequence tags (ESTs) of the Collembola Folsomia candida feeding on mixed vs. single diets. Aspergillus nidulans wildtype (WT; Ascomycota) able to produce secondary metabolites including sterigmatocystin (ST) and a knockout mutant with reduced secondary metabolism (A. nidulans ?LaeA) were combined with the high quality fungus Cladosporium cladosporioides as mixed diets or offered as single diets. We hypothesized that (i) A. nidulans WT triggers more genes associated with stress responses compared to the A. nidulans ?laeA strain with suppressed secondary metabolism, (ii) C. cladosporioides causes significantly different transcript regulation than the A. nidulans strains ?laeA and WT, and (iii) mixed diets will cause significantly different transcript expression levels than single diets. All three hypotheses are generally supported despite the fact that many functions of the affected ESTs are unknown. The results bring molecular evidence for the existence of a link between fungal secondary metabolites and responses in springtails supporting the hypothesis that fungal secondary metabolites act as a shield against fungivory. Twenty-three day old Folsomia candida were fed ad libitum for five days to fungal cuts respectively Cladosporium cladosporoides, Aspergillus nidulans WT, Aspergillus nidulans ?LaeA and two mixed diets of C.cladosporoides/A. nidulans WT (mix 1) and C. cladosporoides/A. nudlans ?LaeA (mix2) respectively. Four biological replicates were used for every treatment and a dye swap was used with the Cy3/Cy5 labels. This resulted in 20 samples which were analysed in 10 hybridisations executed in an interwoven loop design. The C. cladosporoides diet was used as the reference in the data analysis.

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Integrated nutrigenomic and metabolomic analysis of Africans with variable diet

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