Appropriate early microbial colonisation of the gut dramatically affects the incidences of infectious, inflammatory and autoimmune diseases, a concept embraced by the ‘Hygiene Hypothesis’. Hence, factors which influence microbial colonisation and succession during early life have important implications for both human and animal health. This thesis addressed some of the basic principles of the ‘Hygiene Hypothesis’ by investigating how early-life environment impacts on microbial diversity of the adult gut, and how this in turn affects development of the mucosal immune system. The developing pig was used as an experimental model to study host-microbe interactions in early life. The mucosa-adherent microbiota was characterised using both 16S rRNA gene libraries and DGGE and the corresponding host response determined using Affymetrix microarray technology. Initial colonisation of animals derived from two rearing systems with distinct levels of hygiene (outdoor ‘organic/rural’ and indoor ‘hygienic/urban’) was characterised by a highly diverse microbiota that was similar between treatments. These early microbial colonisers were unrelated to those found colonising the adult gut. Establishment of the adult microbiota required continual environmental exposure which led to microbial succession and stabilisation at the adult life-stage. A natural microbiota dominated by Firmicutes reduced both microbial diversity and the number of pathogenic micro-organisms within the gut ecosystem. It also facilitated enhanced innate immune responses. The impact of long-term antibiotic use on the mucosal microbiota was also investigated. This resulted in a sustained disturbance of the gut microbiota which contained phylotypes of a pathogenic phenotype and correlated with altered host immune responses. The work presented supports the concept of the ‘Hygiene Hypothesis’ and has identified windows of opportunity during early life when appropriate manipulation of the mucosal microbiota may enhance immune function and natural disease resistance of the host. Prophylactic administration of broad-spectrum antibiotics in early life is not beneficial to the host.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:531913 |
| Date | January 2009 |
| Creators | Schmidt, Bettina |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=158816 |
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