4.5 Article

Integrated multi-omics of the human gut microbiome in a case study of familial type 1 diabetes

Journal

NATURE MICROBIOLOGY
Volume 2, Issue 1, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/nmicrobiol.2016.180

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Funding

  1. ATTRACT programme grant - Luxembourg National Research Fund (FNR) [ATTRACT/A09/03]
  2. CORE programme grant - Luxembourg National Research Fund (FNR) [CORE/15/BM/10404093]
  3. Aide a la Formation Recherche grants - Luxembourg National Research Fund (FNR) [AFR PHD/4964712, AFR PHD-2013-5824125]
  4. BIOMARKAPD-a project under the aegis of an EU Joint Programme-on Neurodegenerative Diseases (JPND) - Luxembourg National Research Fund (FNR)
  5. 'le plan Technologies de la Sante par le Gouvernment du Grand Duche de Luxembourg' through the Luxembourg Centre for Systems Biomedicine, University of Luxembourg
  6. IBBL under the Personalised Medicine Consortium Diabetes programme

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The gastrointestinal microbiome is a complex ecosystem with functions that shape human health. Studying the relationship between taxonomic alterations and functional repercussions linked to disease remains challenging. Here, we present an integrative approach to resolve the taxonomic and functional attributes of gastrointestinal microbiota at the metagenomic, metatranscriptomic and metaproteomic levels. We apply our methods to samples from four families with multiple cases of type 1 diabetes mellitus (T1DM). Analysis of intra- and inter-individual variation demonstrates that family membership has a pronounced effect on the structural and functional composition of the gastrointestinal microbiome. In the context of T1DM, consistent taxonomic differences were absent across families, but certain human exocrine pancreatic proteins were found at lower levels. The associated microbial functional signatures were linked to metabolic traits in distinct taxa. The methodologies and results provide a foundation for future large-scale integrated multi-omic analyses of the gastrointestinal microbiome in the context of host-microbe interactions in human health and disease.

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