The biotherapeutic potential of Lactobacillus reuteri DPC16 and bovine lactoferrin in controlling some pathogens, genotoxicity and inflammation in the gut: a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Engineering and Advanced Technology at Massey University, Auckland, New Zealand

Abstract

This study investigated the effects of the probiotic bacterium, L. reuteri DPC16, alone and in combination with bovine lactoferrin, on intestinal pathogens, intestinal inflammation and carcinogenesis. Human and animal cellular model systems were designed and applied to this evaluation. The identity of the L. reuteri DPC16 strain was confirmed using 16S rRNA analysis and its ability to produce the antibacterial compound, reuterin. It was able to tolerate pH 2 and physiological concentrations of bile salts in a simulated gastrointestinal tract environment in the presence of protective nutrients. It was able to adhere to a Caco-2 human epithelial monolayer (modelling the human GI tract) and it did not degrade mucin. Both bovine lactoferrin and L. reuteri DPC16 inhibited the growth of the intestinal pathogens Listeria monocytogenes, Staphylococcus aureus, Salmonella typhimurium and Escherichia coli O157:H7, with much less effect on tested probiotic bacteria. Together, L. reuteri DPC16 and bovine lactoferrin showed synergistic inhibitory effects. L. reuteri DPC16 was also able to remove indole from faecal water. Using human/animal cellular model systems, combined with the use of E. coli endotoxin and genotoxic factors present in faecal water, bovine lactoferrin was shown to down-regulate inflammation by affecting the signalling pathway on immune receptors that recognize the endotoxin, while both bovine lactoferrin and strain DPC16 were shown to have the potential to prevent epithelial cell DNA damage. The study has demonstrated several significant properties of L. reuteri DPC16 and bovine lactoferrin, including antibacterial, antigenotoxic, and anti-inflammatory activities, and possible mechanisms for these activities have been proposed. Based on the information obtained from this work, a combination of the probiotic L. reuteri DPC16 and bovine lactoferrin could possibly be developed as a novel probiotic formula for human consumption, to maintain beneficial bacteria while controlling harmful bacteria in the GI tract. However, advanced in vitro model systems and in vivo studies are suggested to confirm these findings in order to consider the feasibility of commercialisation.