Scientists target probiotic potential

University of Leeds scientists are giving an insight into a possible future of pro and prebiotics with GM probiotic bacteria that can stimulate the immune system when 'switched on' by specific prebiotic sugar.

Speaking exclusively to DairyReporter sister site, NutraIngredients.com, lead researcher Professor Simon Carding said that the research could be seen as the next stage in the development of probiotic and prebiotic therapy.

"The primary purpose of our research is to generate a means of delivering biotherapeutic agents to the body via the gut the production of which can be controlled by food-additives," said Carding.

"In this regard our approach can be considered synbiotic. The food additive, xylan, is absolutely essential for the genetically engineered probiotic bacteria to function in the colon. This is analogous to current prebiotic approaches to improving intestinal health.

"This is moving away from the 'shot-gun' approach to targeting specific bacteria," he said.

The crux of the research centres on administering the probiotic, a genetically modified form of a selected Bacteroides strain, and then administering xylan, a sugar found naturally in tree bark and already consumed in small amounts in the diet, which stimulates the growth of the GM probiotic to produce specific proteins that can stimulate the immune system in the intestine.

The xylan could be considered a prebiotic in its own right, said Prof. Carding, since it does stimulate the parental Bacteroides strain, from which the GM probiotic is derived.

The discovery, which has been patented, is currently in the animal testing phase that will continue for another 12 to 16 months, and Carding said that within two years human studies may have started.

For the animal studies, the GM probiotic is being delivered in a solution, while the prebiotic is being delivered in drinking water. The xylan could be delivered and palatable in an orange juice solution.

Simultaneous delivery of the pro- and prebiotic may also be possible, he said. "We think that would work."

While the work is currently focussed on inflammatory bowel disease (IBD), Prof. Carding told this website that they have already started looking at the applicability of the technique to shrink tumours in the colon.

There are no problems with spreading the bacteria, said Prof. Carding, since it is oxygen sensitive and would be dead within 48 hours of being excreted. The bacterial protein production can also be 'switched off' by stopping consumption of the sugar.

The xylan also has no toxicity concerns whatsoever, he said, and that he concentrations needed to stimulate the probiotic was relatively low.

"The ability to control the production of biotherapeutical agents in this way is unique and potentially has many applications in both improving the health of normal individuals and [for] a variety of diseases," Prof. Carding told this website.

"For example, this approach could be used to deliver factors capable of stimulating the development of the immune system in the gut in young animals, improving their ability to resist infection at a critical time in their development," he said.

This principle of stimulating and accelerating the development of the immune system may also be eventually applicable to humans, said Carding.

"It could also be used to deliver immunomodulatory agents that prevent or limit food related hypersensitivity reactions. Another possibility is the production of factors that promote or inhibit the growth of other beneficial or potentially harmful commensal bacteria," he said.

There are challenges in the continued development of the technique, most notably the use of the GM-tag for the bacteria which would create a barrier for consumer acceptance from a food source, particularly in Europe and most notably in the UK.

The research, which started about two and a half years ago, is sponsored by the Medical Research Council and the University of Leeds technology transfer partner, Techtran.

The most studied prebiotics to date are inulin and oligofructose, with Belgium's Orafti influential in building the science behind inulin and oligofructose, backing research into potential benefits for a variety of health conditions ranging from bones to colorectal cancer, from immunity to satiety and weight management.

Probiotics have mostly focussed on the lactoabacillus strains of gut bacteria and most foods containing probiotic bacteria are found in the refrigerated section of supermarkets as the bacteria is destroyed by heat and other processing conditions.

This has given the dairy sector, already used to handling live bacteria for the manufacture of yoghurt, a major advantage in probiotic foods - probiotic drinking yoghurts are currently the fastest growing dairy product in Europe.