title: Environmentally-acquired bacteria influence microbial diversity and natural innate immune responses at gut surfaces.
abstract: BACKGROUND
  Early microbial colonization of the gut reduces the incidence of infectious, inflammatory and autoimmune diseases. Recent population studies reveal that childhood hygiene is a significant risk factor for development of inflammatory bowel disease, thereby reinforcing the hygiene hypothesis and the potential importance of microbial colonization during early life. The extent to which early-life environment impacts on microbial diversity of the adult gut and subsequent immune processes has not been comprehensively investigated thus far. We addressed this important question using the pig as a model to evaluate the impact of early-life environment on microbe/host gut interactions during development.
  
  
  RESULTS
  Genetically-related piglets were housed in either indoor or outdoor environments or in experimental isolators. Analysis of over 3,000 16S rRNA sequences revealed major differences in mucosa-adherent microbial diversity in the ileum of adult pigs attributable to differences in early-life environment. Pigs housed in a natural outdoor environment showed a dominance of Firmicutes, in particular Lactobacillus, whereas animals housed in a hygienic indoor environment had reduced Lactobacillus and higher numbers of potentially pathogenic phylotypes. Our analysis revealed a strong negative correlation between the abundance of Firmicutes and pathogenic bacterial populations in the gut. These differences were exaggerated in animals housed in experimental isolators. Affymetrix microarray technology and Real-time Polymerase Chain Reaction revealed significant gut-specific gene responses also related to early-life environment. Significantly, indoor-housed pigs displayed increased expression of Type 1 interferon genes, Major Histocompatibility Complex class I and several chemokines. Gene Ontology and pathway analysis further confirmed these results.
  
  
  CONCLUSIONS
  Early-life environment significantly affects both microbial composition of the adult gut and mucosal innate immune function. We observed that a microbiota dominated by lactobacilli may function to maintain mucosal immune homeostasis and limit pathogen colonization.
authors.affiliation: Gut Immunology Group, University of Aberdeen, Rowett Institute of Nutrition and Health, Greenburn Road, Aberdeen AB21 9SB, UK. I.Mulder@abdn.ac.uk
authors.forename: Imke E
authors.initials: IE
authors.lastname: Mulder
authors.forename: Bettina
authors.initials: B
authors.lastname: Schmidt
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Stokes
authors.forename: Marie
authors.initials: M
authors.lastname: Lewis
authors.forename: Mick
authors.initials: M
authors.lastname: Bailey
authors.forename: Rustam I
authors.initials: RI
authors.lastname: Aminov
authors.forename: James I
authors.initials: JI
authors.lastname: Prosser
authors.forename: Bhupinder P
authors.initials: BP
authors.lastname: Gill
authors.forename: John R
authors.initials: JR
authors.lastname: Pluske
authors.forename: Claus-Dieter
authors.initials: CD
authors.lastname: Mayer
authors.forename: Corran C
authors.initials: CC
authors.lastname: Musk
authors.forename: Denise
authors.initials: D
authors.lastname: Kelly
mesh_terms: D000818:Animals; D044822:Biodiversity; D004777:Environment; D007082:Ileum / Q000276:immunology / Q000382:microbiology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology*; D007778:Lactobacillus / Q000145:classification / Q000235:genetics*; D023421:Models, Animal; D020411:Oligonucleotide Array Sequence Analysis; D010802:Phylogeny; D012336:RNA, Ribosomal, 16S / Q000032:analysis; D017423:Sequence Analysis, RNA; D013552:Swine / Q000382:microbiology*
chemical_list: D012336:RNA, Ribosomal, 16S