title: Defining the microbial transcriptional response to colitis through integrated host and microbiome profiling.
abstract: The gut microbiome is significantly altered in inflammatory bowel diseases, but the basis of these changes is not well understood. We have combined metagenomic and metatranscriptomic profiling of the gut microbiome to assess modifications to both bacterial community structure and transcriptional activity in a mouse model of colitis. By using transcriptomic analysis of colonic tissue and luminal RNA derived from the host, we have also characterised how host transcription relates to the microbial transcriptional response in inflammation. In colitis, increased abundance and transcription of diverse microbial gene families involved in responses to nutrient deprivation, antimicrobial peptide production and oxidative stress support an adaptation of multiple commensal genera to withstand a diverse set of environmental stressors in the inflammatory environment. These data are supported by a transcriptional signature of activated macrophages and granulocytes in the gut lumen during colitis, a signature that includes the transcription of the key antimicrobial genes S100a8 and S100a9 (calprotectin). Genes involved in microbial resistance to oxidative stress, including Dps/ferritin, Fe-dependent peroxidase and glutathione S-transferase were identified as changing to a greater extent at the level of transcription than would be predicted by DNA abundance changes, implicating a role for increased oxygen tension and/or host-derived reactive oxygen species in driving transcriptional changes in commensal microbes.
authors.affiliation: Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
authors.forename: Nicholas Edward
authors.initials: NE
authors.lastname: Ilott
authors.affiliation: Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.|Institute for Tumor Biology and Experimental Therapy, Georg-Speyer-Haus, Frankfurt am Main, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Bollrath
authors.affiliation: Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
authors.forename: Camille
authors.identifier: 0000-0003-0971-8310
authors.initials: C
authors.lastname: Danne
authors.affiliation: The Francis Crick Institute, Mill Hill Laboratory, London, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Schiering
authors.affiliation: Translational Gastroenterology Unit, Experimental Medicine, Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Shale
authors.affiliation: Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
authors.forename: Krista
authors.initials: K
authors.lastname: Adelmann
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Krausgruber
authors.affiliation: Computational Genomics Analysis and Training (CGAT), MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
authors.forename: Andreas
authors.initials: A
authors.lastname: Heger
authors.affiliation: Computational Genomics Analysis and Training (CGAT), MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
authors.forename: David
authors.initials: D
authors.lastname: Sims
authors.affiliation: Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
authors.forename: Fiona
authors.initials: F
authors.lastname: Powrie
mesh_terms: D000818:Animals; D001419:Bacteria / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D003092:Colitis / Q000235:genetics* / Q000276:immunology / Q000382:microbiology*; D005260:Female; D000069196:Gastrointestinal Microbiome; D020869:Gene Expression Profiling; D006801:Humans; D056186:Metagenomics; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D001426:Bacterial Proteins