IMMUNOGLOBULIN AND NONIMMUNOGLOBULIN COMPONENTS OF HUMAN-MILK INHIBITCLOSTRIDIUM-DIFFICILE TOXIN A-RECEPTOR BINDING

Clostridium difficile is isolated from the intestinal tracts of > 50% of healthy infants. The mechanism by which intestinal colonisation of infants by toxigenic C. difficile is generally asymptomatic is unknown but may reflect the presence in human milk of neutralising activity a gainst C. difficile toxin A. On this basis, the ability of human milk to inhibit the binding of toxin A to a purified hamster brush border m embrane receptor was determined. Ten milk samples from healthy volunte ers in various stages of lactation inhibited the binding of toxin A to the receptor by an average of 90%. Heating and dialysis did not signi ficantly alter the inhibitory activity of any of the milk samples. Hum an milk protected adult hamsters against a lethal challenge with toxin A but had no effect on the cytotoxic activity of the toxin. SDS-PAGE and ligand blot analyses showed that there were at least four distinct factors in human milk that specifically bound toxin A. Thiophilic ads orption chromatography was used to separate immunoglobulin from non-im munoglobulin components of human milk. IgA was the only immunoglobulin detected in human milk and > 90% of this immunoglobulin was recovered after purification by thiophilic adsorption. Both the unbound non-imm unoglobulin and bound immunoglobulin fractions of human milk inhibited the binding of toxin A to the purified receptor. These results sugges t that human milk may be important in protecting infants against C. di fficile-associated intestinal disease.