title: Integrated multi-omics of the human gut microbiome in a case study of familial type 1 diabetes.
abstract: 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.
authors.affiliation: Luxembourg Centre for Systems Biomedicine, 7 avenue des Hauts-Fourneaux, 4362 Esch-sur-Alzette, Luxembourg.
authors.forename: Anna
authors.initials: A
authors.lastname: Heintz-Buschart
authors.affiliation: Luxembourg Centre for Systems Biomedicine, 7 avenue des Hauts-Fourneaux, 4362 Esch-sur-Alzette, Luxembourg.
authors.forename: Patrick
authors.identifier: http://orcid.org/0000-0001-8698-3770
authors.initials: P
authors.lastname: May
authors.affiliation: Luxembourg Centre for Systems Biomedicine, 7 avenue des Hauts-Fourneaux, 4362 Esch-sur-Alzette, Luxembourg.
authors.forename: Cédric C
authors.identifier: http://orcid.org/0000-0002-1100-1282
authors.initials: CC
authors.lastname: Laczny
authors.affiliation: Luxembourg Centre for Systems Biomedicine, 7 avenue des Hauts-Fourneaux, 4362 Esch-sur-Alzette, Luxembourg.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Lebrun
authors.affiliation: Integrated BioBank of Luxembourg, 6 rue Nicolas Ernest Barblé, 1210 Luxembourg, Luxembourg.
authors.forename: Camille
authors.initials: C
authors.lastname: Bellora
authors.affiliation: Luxembourg Centre for Systems Biomedicine, 7 avenue des Hauts-Fourneaux, 4362 Esch-sur-Alzette, Luxembourg.
authors.forename: Abhimanyu
authors.initials: A
authors.lastname: Krishna
authors.affiliation: Luxembourg Centre for Systems Biomedicine, 7 avenue des Hauts-Fourneaux, 4362 Esch-sur-Alzette, Luxembourg.
authors.forename: Linda
authors.initials: L
authors.lastname: Wampach
authors.affiliation: Luxembourg Centre for Systems Biomedicine, 7 avenue des Hauts-Fourneaux, 4362 Esch-sur-Alzette, Luxembourg.|Department of Internal Medicine II, Saarland University Medical Center, 66421 Homburg, Germany.|Centre Hospitalier Emile Mayrisch, Rue Emile Mayrisch, 4240 Esch-sur-Alzette, Luxembourg.
authors.forename: Jochen G
authors.initials: JG
authors.lastname: Schneider
authors.affiliation: Integrated BioBank of Luxembourg, 6 rue Nicolas Ernest Barblé, 1210 Luxembourg, Luxembourg.
authors.forename: Angela
authors.initials: A
authors.lastname: Hogan
authors.affiliation: Luxembourg Centre for Systems Biomedicine, 7 avenue des Hauts-Fourneaux, 4362 Esch-sur-Alzette, Luxembourg.|Clinique Pédiatrique - Centre Hospitalier de Luxembourg, 4 rue Nicolas Ernest Barblé, 1210 Luxembourg.
authors.forename: Carine
authors.initials: C
authors.lastname: de Beaufort
authors.affiliation: Luxembourg Centre for Systems Biomedicine, 7 avenue des Hauts-Fourneaux, 4362 Esch-sur-Alzette, Luxembourg.
authors.forename: Paul
authors.initials: P
authors.lastname: Wilmes
mesh_terms: D003922:Diabetes Mellitus, Type 1 / Q000382:microbiology*; D000069196:Gastrointestinal Microbiome; D041981:Gastrointestinal Tract / Q000382:microbiology*; D020869:Gene Expression Profiling; D006801:Humans; D056186:Metagenomics; D064307:Microbiota; D020543:Proteome / Q000032:analysis
chemical_list: D020543:Proteome