The role of soluble dietary plant fibre (non-starch polysaccharides) in maintenance of intestinal health and prevention of diarrhoeal disease

A high intake of dietary fibre has long been thought to promote intestinal health through accelerated transit time, short-chain fatty acid production and prebiotic promotion of Bifidobacteria [1-3]. An alternative hypothesis will be investigated by the 4 year PhD CASE student: that non-digested fibre polysaccharides may have beneficial impact via their ability to inhibit potentially harmful interactions between bacteria and the gut epithelium. Bacteria-epithelial adherence is often mediated by lectin-carbohydrate interactions and it is plausible that the diverse oligosaccharide structures present in soluble plant fibres will often block these interactions. We have already shown that soluble plant fibre (non-starch polysaccharide, NSP) at levels achievable in vivo, block interaction of human mucosal Escherichia coli (E. coli) isolates to intestinal epithelium [4,5]. Moreover, the juice from boiled green bananas has been found effective in a variety of diarrhoeal diseases [6]. Enterotoxigenic E. coli (ETEC) is the commonest cause of travellers' diarrhoea and Clostridium difficile, a major cause of antibiotic-associated diarrhoea (8,324 recorded deaths in England & Wales, 2007). Close proximity of ETEC and C. difficile to the host epithelium is almost certainly necessary to produce toxic effects [7] and preventing these interactions should therefore be of therapeutic benefit. Plantain (Musa spp., ie banana) has the greatest efficacy of all fibre so far tested in our lab and is now in clinical trial as a therapeutic agent in Crohn's patients. Recently, we have shown plantain and broccoli NSP to be effective in reducing adhesion to epithelial cells of a number of diarrhoeal pathogens including Salmonella, ETEC & C. difficile [manuscript submitted]. The CASE student, during MRes and year 1 of the PhD, will investigate soluble plant NSP (including plantain, broccoli, various fruits with potential inhibitory action) for their efficacy at blocking adhesion of C. difficile and ETEC to colonocytes, as per [4,8]. The principal aim will be to identify fibre fractions/structures which have particular efficacy at blocking recruitment of these organisms with a view to subsequent development as functional foods that could promote health in people at risk - ie travellers or people taking antibiotics. Provexis will provide expertise in plant cell wall fractionation and of NSP components as part of a BBSRC LINK study focused on prevention of Salmonella infection in chicks (BB/G01969X/1) with the aim of identifying oligosaccharide structures that have particular inhibitory potency. This fibre fractionation will be conducted in laboratories on site at University of Liverpool so the PhD student will work easily between the two partners. In year 2, these oligosaccharides will be further tested on bacterial adherence to colonoscopic biopsy tissue obtained from healthy patients with informed consent. Adherence will be assessed by culture, and also by confocal and electron microscopy. Use of ex vivo human villus epithelium mounted in Ussing chambers, will allow for assessment of the effects of fibre oligosaccharides on mucosal barrier integrity, electrophysiology (Isc, Gt etc) and electrogenic Cl- secretion, a feature of enterotoxic secretory diarrhoea [9]. To identify the molecular moieties underlying fibre-C. difficile/ETEC interaction, NSP fractions will also be screened during year 3 for pathogen binding using glycoarrays [10] and finally (with training and expertise provided by Provexis) subjected to spectroscopic characterisation. [1] Lancet 197,2:1408-12; [2] Aliment. Pharm. Ther. 2008;27:104-19; [3] Aliment. Pharm. Ther. 2006;24:701-14; [4] Gastroenterology 2004,127:80-93; [5] Roberts et al. Gut 2010, in press (doi:10.1136/gut.2009.195370); [6] Gastroenterology 2001: 121,554-60; [7] Microbiol. Rev. 1996,167-215; [8] J. Med. Microbiol. 2001,50:526-34; [9] Am. J. Physiol. 2009,296:G1151-66; [10] Chembiochem 2008,9;1568-75