Dietary fructo-oligosaccharide modulates large intestinal inflammatory responses to Clostridium difficile in antibiotic-compromised mice

Intestinal inflammatory parameters and microbiological changes were examined in antibiotic-compromised mice in response to Clostridium difficile, a causative agent of pseudomembranous colitis. C57BL/6NHsd mice were treated orally with a broad- spectrum antibiotic and then fed a low-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 controls (no antibiotic) in the Ensure- fed group. However, when the diet was supplemented with FOS, total anaerobe concentrations were higher for antibiotic-treated mice than for controls. Levels of C. difficile were higher for antibiotic-treated animals on day 12 in the FOS-supplemented group and in both diet groups 4 d post-infection. Toxin A titres were significantly elevated 1 d and 4 d post C. difficile challenge only in the antibiotic treated mice not receiving FOS. Antibiotic effects on intestinal immune cell populations were also dependent on diet. Dendritic and γδ T-cell numbers in the caecum were increased by antibiotic treatment in mice fed Ensure only, while tissue concentrations of the bioactive lipid prostaglandin E₂ were decreased. Alternatively, antibiotic treatment increased macrophage numbers in the caecum of FOS-supplemented mice without affecting dendritic and γδ T-cell numbers or prostaglandin E₂ concentrations. Notably, alterations in immune parameters in response to antibiotic were observed predominantly in the caecum, where bacterial density is highest and where C. difficile-induced lesions are localised in the mouse.