Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.701105
Title: Infection by the gastrointestinal parasite Trichuris muris : defining the microbiota of the parasite and the host
Author: White, Emily Claire
ISNI:       0000 0004 5990 1639
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2016
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Abstract:
Intestinal dwelling parasites live in close association with the complex microbiota that inhabit our intestinal tracts. The intestinal helminth, Trichuris muris, depends on these bacteria for egg hatching and successful establishment of infection within the epithelium of the caecum and colon. Infection causes significant alterations to the host intestinal microbiota, including a decrease in bacterial diversity and shifts in proportions of certain bacterial groups. This is accompanied by a decrease in Foxp3+ regulatory T cells and changes to the metabolic potential of the host microbiota, consequently impacting host health. However, the factor(s) driving these changes and the existence and role of its own intestinal microbiota is unknown. Infection of C57BL/6 and immunodeficient SCID mice with a high dose (~ 200 embryonated eggs) and a low dose (~ 20 embryonated eggs) of T. muris was used to determine the impact of worm burden and the adaptive immune system on the host intestinal microbiota, in comparison to naïve controls. Microbiota analysis was performed by 16S rRNA gene denaturing gradient gel electrophoresis (DGGE) and Illumina sequencing. This revealed that infection-induced microbiota changes were dose dependent and high level infection caused an increase in the Bacteroidaceae and Enterobacteriaceae families, independently of the host adaptive immune system. Development of a surface sterilisation protocol enabled the internal T. muris microbiota to be analysed by 16S rRNA gene DGGE and fluorescence in situ hybridisation (FISH). The resulting data indicated that T. muris requires its own diverse intestinal microbiota that is derived from, but distinct to, that of its host. A core microbiota is selected and maintained by the parasite regardless of the surrounding host microbiota. The parasite microbiota is important for its fitness, shown in vitro using an antibiotic motility assay and in vivo using germ free (GF) mice. Furthermore, infection with T. muris causes a significant reduction in caecal butyrate concentrations and consequently a decrease in the expression of butyrate transporters in caecal tissue. Interestingly, the T. muris microbiota is able to produce the short-chain fatty acid (SCFA) butyrate, which the parasite is unable to make itself yet secretes into its local environment. Together these strategies promote the long term survival of T. muris within the intestinal niche, adding a new level of complexity to the interaction between the pathogen, the host and their respective microbiotas that underpins successful chronic nematode infection.
Supervisor: Grencis, Richard ; Roberts, Ian ; Robertson, David Sponsor: BBSRC
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.701105  DOI: Not available
Keywords: Microbiota ; Trichuris ; Helminth ; Infection
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