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发表于 2009-12-16 09:08:15
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BMC Biology 2009, 7:79doi:10.1186/1741-7007-7-79
Environmentally-acquired bacteria influence microbial diversity and natural innate immune responses at gut surfaces
Imke E Mulder* 1 , Bettina Schmidt* 1 , Christopher R Stokes2 , Marie Lewis2 , Mick Bailey2 , Rustam I Aminov1 , James I Prosser3 , Bhupinder P Gill4 , John R Pluske5 , Claus-Dieter Mayer6 , Corran C Musk1 and Denise Kelly1
1Gut Immunology Group, University of Aberdeen, Rowett Institute of Nutrition and Health, Greenburn Road, Aberdeen AB21 9SB, UK
2Veterinary Pathology, Infection & Immunity, Langford House, Langford, Bristol, BS40 5DU, UK
3Institute of Biological and Environmental Sciences, University of Aberdeen, St Machar Drive, Aberdeen AB24 3UU, UK
4Agricultural and Horticultural Development Board, Winterhill House, Snowdon Drive, Milton Keynes MK6 1AX, UK
5School of Veterinary and Biomedical Sciences, Murdoch University, Murdoch, WA 6150, Australia
6Biomathematics & Statistics Scotland, University of Aberdeen, Rowett Institute of Nutrition and Health, Greenburn Road, Aberdeen AB21 9SB, UK
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.
Conclusion
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. |
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