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Could GM offer the next generation of probiotics?

By Stephen Daniells , 21-Aug-2009

A look into the probiotic crystal ball reveals that genetically engineered "friendly" bacteria could be switched on by specific prebiotic sugar, possibly leading to a new generation of pre- and probiotic products.

The innovation focuses on administering the strain, a genetically modified Bacteroides ovatus, 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 bacteria to produce specific proteins that can stimulate the immune system in the intestine.

New research in Gut indicated that the engineered strain was effective as a therapy in animals with colitis, one of the major forms of inflammatory bowel disease.

Speaking to NutraIngredients.com, lead researcher Professor Simon Carding said that, while the initial application as published in Gut is medical, the bacteria itself has potential probiotic properties and “there is therefore the potential to exploit this further as a food additive”.

“Also, xylan the plant polysaccharide that is used to activate and regulate the bacteria in the gut is a prebiotic, extensively used in Japan to supplement everything from baby food to toothpaste,” he said.

Prof. Carding, from the Institute of Food Research and the University of East Anglia Medical School, said the xylan could be considered a prebiotic in its own right since it does stimulate the parental Bacteroides strain, from which the GM strain is derived.

And this leads to three potential areas for the technology to be used as a food additive, he said. Firstly, the parental, non-GM version of the bacteria could form part of a probiotic formulation. Secondly, xylan can be used as a prebiotic, particularly in beverage formulations (it is very well tolerated by animals when added to their drinking water, said Prof Carding). Thirdly, the parental bacteria and xylan could be used together as a synbiotic.

How does it work?

When exposed to xylan the engineered B. ovatus works produces a protein, called KGF-2, directly to the damaged cells that line the gut, unlike other treatments which can cause unwanted side effects. The medication could be controlled by controlling the ingestion of the xylan, said Prof Carding, and this could perhaps be done via a drink.

“This is the first time that anyone has been able to control a therapeutic protein in a living system using something that can be eaten,” said Prof Carding. “The beneficial bugs could be activated when they are needed.”

This specific application results in a decrease in rectal bleeding, an acceleration of gut healing, and a reduction in inflammation, they said. It may also have the potential to prevent colitis.

Safety first

There are no problems with spreading the bacteria, said Prof. Carding, since it retains sensitivity to broad spectrum antibiotics. It is oxygen sensitive and would rapidly die upon contact with environmental oxygen, he added. 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 the concentrations needed to stimulate the probiotic was relatively low.

What’s next?

Prof Carding confirmed that work was ongoing in this area and they are currently seeking the funding needed for Phase I trails. He also said that his team are developing strains for use in other applications including colon cancer, vaccine (anti-viral) delivery, and antimicrobials that can redress imbalances in the communities of gut bacteria present in disease states.

No industrial partner is currently working with the IFR team. However, Prof Carding did say that such partners are actively being sought seeking through Plant Bioscience Limited (PBL), which on behalf of the Institute of Food Research develops innovative technologies.

The work was funded by the Medical Research Council and the Royal College of Surgeons, and by Techtran. The Institute of Food Research is an institute of Biotechnology and Biological Sciences Research Council.

Source: Gut
Xylan-regulated delivery of human keratinocyte growth factor-2 to the inflamed colon by the human anaerobic commensal bacterium Bacteroides ovatus”

Authors: Z.Z.R. Hamady, N. Scott, M.D. Farrar, J.P.A Lodge, K.T. Holland, T. Whitehead, S.R. Carding

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