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Title: Development of a system for modelling of the human large intestine
Author: Spratt, Philip.
ISNI:       0000 0001 3475 5864
Awarding Body: University of Reading
Current Institution: University of Reading
Date of Award: 2003
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Laboratory model This project covers the design and production of a new continuous culture system for the modelling of the human large intestine. A single stage tubular model of the human ascending colon was produced through the continued adaptation of preliminary models. This single- stage model consisted of a membrane based fermenter used in conjunction with an aqueous polyethylene glycol solution for water and metabolite removal and the pH control of the fermentation media. The design also incorporated a module for sampling media during the course of the fermentation. This single stage model was characterised through fermentations using a faecal inoculum. Properties monitored were the ability to control media pH indirectly through the transfer of solutes across a membrane, the degree of water removal through the membrane and the degree of substrate utilisation in the system. The ability of the fermenter to maintain the growth of bacterial species present in the gut, at a flow rate analogous to that through the human colon was also monitored. The membrane system was found to facilitate the control of the pH in the fermentation media. The removal of water and short chain fatty acids from fermentation media was also observed. Large and stable numbers of colonic bacteria were maintainable in the fermenter. The single- stage model provided the basis for a three- stage tubular model of the large intestine which was produced and analysed by means of inoculation with a faecal sample and monitoring its performance during a fermentation. The 3- stage tubular system was found to give a good representation of conditions in the human large intestine. Numbers of each bacterial group studied were consistently higher in the membrane system than in an existing gut model system (Macfarlane et al. 1998). This suggested that the tubular membrane model provided a better environment for bacterial growth and a better representation of the actual colonic micro flora. The new system was found to be capable of maintaining total bacterial numbers of 5.0 ± 4.8 xl010 bacterial ml in the first fermenter section. Concentrations of short chain fatty acids throughout the system were found to be similar to those associated with the corresponding regions of the human colon. The membrane system was capable of controlling the pH throughout the fermentation media and providing a degree of short chain fatty acid and water removal. The model was capable of removing 64% of incoming media across the membranes, the majority of which can be assumed to be water. This provided a good representation of the degree of water removal that occurs in the human colon itself. Mathematical Model To supplement the practical model, mixing was characterised in a tubular fermenter with intermediate flow regime. To this aim, diffusion-convection and diffusion models were solved numerically to provide the theoretical residence time distribution ,in tubular fermenters, in intermediate flow regimes. The diffusion-convection model was validated using the experimental results obtained from step tracer experiments in a tubular vessel at different flow rates and was shown to correlate well with experimental data. The variance ratio between the two models was calculated allowing its use as a correction factor. This allows the use of the diffusion model for the characterisation of mixing in tubular fermenters that are associated with low Reynolds numbers, such as the new gut model system.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available