Researchers at the University of Leeds have genetically modified a common gut bacterium to respond to a sugar and produce a treatment for Inflammatory Bowel Disease (IBD).
Professor Simon Carding, chair of molecular immunology at the University of Leeds, modified Bacteroides ovatus to release human growth factors, called cytokines, that repair the epithelial cells found in the lining of the gut, reducing the inflammation caused by IBD.
"There are one or two cytokine therapies in clinical trials, but the problem is that most of the current agents are administered directly into the blood stream. Very little of the drug gets to the damaged tissues in the gut; most stays in the blood where they can have very different effects. These drugs are also very delicate and need to be delivered to the target directly," Professor Carding told sister site, DrugResearcher.com.
While bacteria and viruses have been used to deliver drugs in this way before, the major problem has always been in controlling the production of the drugs. Carding has found a novel answer to this by linking the gene in the bacteria that breaks down xylan with the human gene that produces cytokines.
"Current bacteria and virus delivery systems produce their drugs non-stop, but for many treatments there is a narrow concentration range at which drugs are beneficial," he continued.
"Outside of this, the treatment can be counterproductive and make the condition worse. It's vitally important to be able to control when and how much of the drug is administered and we believe our discovery will provide that control."
Xylan is a sugar that is mainly found in tree bark, and naturally present in food in only low concentrations and not part of most people's diets. The bacteria behave as normal until they encounter the xylan, which triggers them to produce the cytokines. A patient can control the dose they receive by controlling how much xlylan they eat; when the xylan runs out cytokine production stops.
Bacteroides ovatus are widely distributed in the animal kingdom and is one of the 'good' bacteria that helps to breakdown plant material to provide energy to the body.
Carding also has plans to extend the applications into many other gut problems, including colorectal cancer.
"We're already looking at using the same technique for colorectal cancer, as we believe we could modify the bacteria to produce factors that will reduce tumour growth."
Carding envisages even wider applications: "Treatment of diseases elsewhere in the body might also be possible as most things present in the gut can get taken into the blood stream." "We are currently looking at bacteria that can release naturally occurring drug factors that shut down the blood supply to tumours, restricting their growth and preventing them spreading."
"We envisage the use of the bacteria as an adjuvant cancer therapy although we could try to combine it with another strain that would activate cytotoxic T-cells, allowing us to kill the cancerous cells as well."
The technique is currently being tested in preclinical trials and Carding envisages being able to enter the clinic in one to two years. He did mention that one study that still needs to be conducted was for how long the bacteria persist in the gut.