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Metagenomics and metabolomics studies of patients with Anorexia Nervosa to identify intestinal microbial mechanisms contributing to pathogenesis

Objective

Background: Anorexia nervosa (AN), a complex disorder characterized by self-starvation with obsessive thoughts of food resulting in extreme weight loss, carries the highest fatality rate of any psychiatric disease. There is no evidence that the prognosis of AN has improved throughout the 20th century. The role of an altered gut microbiota in the pathogenesis of various human disorders is under intense scrutiny since gut bacteria contribute to metabolic, neurological and immune pathways in the host. Recent advances in microbial DNA sequencing technologies and advanced bioinformatics combined with access to comprehensive microbial gene catalogues have resulted in accurate quantitative metagenomics analysis of the gut microbiota, the impact of which on host biology can be estimated by untargeted metabolomics.
Objectives: At deep taxonomic and functional levels to identify which parts of the gut microbiome are altered in women with drug-naïve AN compared with a group of age-matched controls and to elucidate how an aberrant AN microbiome relates to AN phenotypes through the serum metabolome. Potential causality is explored in germ-free mice transplanted with stools from AN patients and controls.
Approach: The study sample consists of 152 carefully phenotyped women. Eighty have AN. Deep shot-gun sequencing of microbial DNA has been done on stools from all women. Similarly, fasting serum samples from all individuals have been analyzed applying state-of-the art untargeted metabolomics and lipidomics. In the outlined research program I will test the hypothesis that an aberrant gut microbiome relate to AN phenotypes via an altered serum metabolome. In mechanistic studies of germ-free mice I will examine if stools from AN patients affect body composition of this species as suggestive evidence of causality of AN gut microbiota.
Perspectives: Clarifying intestinal microbiome-metabolome interactions will open novel avenues to understand aspects of AN pathogenesis.

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MSCA-IF-EF-ST - Standard EF

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(opens in new window) H2020-MSCA-IF-2017

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Coordinator

KOBENHAVNS UNIVERSITET
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 212 194,80
Address
NORREGADE 10
1165 KOBENHAVN
Denmark

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Region
Danmark Hovedstaden Byen København
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 212 194,80
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