Dietary Fructo-oligosaccharide Modulates Large Intestinal Inflammatory Responses toClostridium difficilein Antibiotic-compromised Mice

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Abstract
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®) 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 litres 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.