DIETARY FRUCTO-OLIGOSACCHARIDE MODULATES LARGE INTESTINAL INFLAMMATORY RESPONSES TO CLOSTRIDIUM-DIFFICILE IN ANTIBIOTIC-COMPROMISED MICE

Intestinal inflammatory parameters and microbiological changes were ex amined in antibiotic-compromised mice in response to Clostridium diffi cile, a causative agent of pseudomembranous colitis. C57BL/6NHsd mice were treated orally with a broad- spectrum antibiotic and then fed a l ow-residue diet (Ensure(R)) with or without the fermentable substrate fructo-oligosaccharide (FOS). Animals were infected with C. difficile 6 d after antibiotic treatment. Three days after antibiotic challenge, total anaerobes were lower for antibiotic-treated mice than for contr ols (no antibiotic) in the Ensure-fed group. However, when the diet wa s supplemented with FOS, total anaerobe concentrations were higher for antibiotic-treated mice than for controls. Levels of C. difficile wer e higher for antibiotic-treated animals on day 12 in the FOS-supplemen ted group and in both diet groups 4 d post-infection. Toxin A titres w ere significantly elevated 1 d and 4 d post C. difficile challenge onl y in the antibiotic treated mice not receiving FOS. Antibiotic effects on intestinal immune cell populations were also dependent on diet. De ndritic and gamma delta T-cell numbers in the caecum were increased by antibiotic treatment in mice fed Ensure only, while tissue concentrat ions of the bioactive lipid prostaglandin E(2) were decreased. Alterna tively, antibiotic treatment increased macrophage numbers in the caecu m of FOS-supplemented mice without affecting dendritic and gamma delta T-cell numbers or prostaglandin E(2) concentrations. Notably, alterat ions in immune parameters in response to antibiotic were observed pred ominantly in the caecum, where bacterial density is highest and where C. difficile-induced lesions are localised in the mouse.