Genetically modified bacterium as remedy for intestinal diseases

Researchers from the Flanders Interuniversity Institute for Biotechnology (VIB) at Ghent University are joining the fight against chronic intestinal disease with a genetically modified bacterium (Lactococcus lactis).

The modified bacterium is able to produce medication right in the intestine. This is often the crux of the problem: a number of medicines are presumed to be effective, but until now it has been impossible to get them into the intestine in a simple manner. The researchers have shown that the genetically modified bacterium is able to manufacture the potential medicine, Trefoil Factors, in the intestines of diseased mice.

Chronic intestinal inflammations, such as Crohn’s disease, are occurring with increasing frequency, striking young adults in particular. In an advanced stage of such inflammations, patients can eat only via catheters.

Crohn’s disease has been on the rise in recent years: it is estimated that in Western Europe 2 persons in 1000 suffer from it. This typically Western disease appears almost exclusively in the industrialized world, and more often in cities than in the country.

In its natural form, the Lactococcus lactis bacterium is a house, garden, and kitchen bacterium. Dairy product manufacturers use large quantities of the bacterium to ferment milk when making hard cheeses. The VIB researchers came up with the idea of using the bacterium as a producer of a remedy for intestinal inflammations. They placed the DNA with the code for a potential medicine inside the DNA of the bacterium. The genetically modified bacterium could then produce the therapeutic protein itself. In 2003, the VIB researchers succeeded in having the Lactococcus manufacture the anti-inflammatory agent IL-10. The IL-10 bacterium shows great promise in the battle against chronic inflammations and is now being tested on patients.

Klaas Vandenbroucke and his VIB colleagues, under the direction of Pieter Rottiers and Erik Remaut, took the earlier research further and placed the mouse gene with the code for mouse ‘trefoil factors’ (TFF) into the Lactococcus. TFF play an important role in the protection and healing of the epithelium − the inner wall − of the stomach- intestinal system. They also play a role in the construction of the stomach-intestinal tract. This structural function ensures that TFF never arrives in the intestine through oral administration, because along the way it attaches itself somewhere in the stomach-intestinal tract. This was also demonstrated in the tests on mice with acute enteritis: oral administration of TFF had no effect, but rectal administration did. Still, neither of the two methods of administration could match the impressive recovery of the mice following oral administration of the TFF bacteria.

The researchers also used the TFF bacteria to treat mice with chronic enteritis, which proved to be successful as well. This research confirms the findings from the earlier VIB research (under the direction of Lothar Steidler and Erik Remaut) concerning the therapeutic action of IL-10 bacteria. Thus, this method of working with genetically modified bacteria offers promising prospects for the treatment of both acute and chronic intestinal inflammation, and it can potentially be extended to other therapeutics as well.