Many people who hear the term gluten intolerance (used in this case to mean celiac disease) wonder how it differs from lactose intolerance. Further, they think there should be a simple treatment like there is for lactose intolerance, an enzyme to break down gluten like lactase breaks down lactose.
An enzyme to help digest gluten is a good idea in principle, but in fact, it is tremendously more complicated than the digestion of lactose. Lactose, or milk sugar, is made up of two simple sugars, glucose and galactose. The missing enzyme only has to break the bonds between the two sugars, and the resulting glucose and galactose are easily digested. Not only that, but many people have at least some of this enzyme left in their intestine. When there isn’t enough lactase, symptoms of lactose intolerance occur because lactose is not absorbed in the small intestine, and gets into the large intestine, causing gas, cramps and diarrhea.
Gluten is a very complicated substance, a protein, made up of many different amino acids in specific sequence. In the case of gluten, the amino acids glutamine and proline account for its stickiness, which is why it is good for making bread and pasta.
It takes many steps to break down gluten into small enough pieces for it to be absorbed. That is not the problem in celiac disease. The problem is that certain pieces of gluten are actually toxic to people with the genetic tendency to have celiac disease. There a number of steps to developing CD that are incompletely understood. Something allows these pieces of gluten (called α‑gliadins) to get through the lining of the small intestine. This may be an infection early in a susceptible individual’s life or some other trigger.
Once these pieces get in, they start a complicated immune response which actually damages the small intestine. Not only can this result in symptoms like diarrhea, gas and cramps, but it can also prevent the body from absorbing essential nutrients. Adults may not have the abdominal symptoms, but may develop the problems from missing out on certain vitamins and minerals they need. They can develop anemia or osteoporosis because of this.
People with celiac disease can already break down gluten into some pieces. An enzyme to break down gluten further would not help unless it completely digested the parts of the gluten molecules that cause problems.
This type of enzyme could be called the “Holy Grail” of celiac disease research, and lots of researchers are trying to develop such a substance.
One group used a unique way to look at this problem. Researchers used computer models to figure out what a potential enzyme would have to be able to do. They published an article with a title that gives an idea of its complexity called “Computational Design of an α‑Gliadin Peptidase” in the Journal of the American Chemical Society late in 2012.
The idea of an enzyme discussed in this article made its way into many mainstream newspapers and websites, implying that they were close to an enzyme like lactase to be used as treatment. In fact, while the research is very exciting, they are nowhere near having such a thing ready for people. The research is about an enzyme designed by computer that has not even been tested on animals. That does not mean it will not work. It means that anything for people is years away.
The researchers looked for an existing enzyme that had been found in a bacteria or other organism that could do these things:
• Work in the acid found in the stomach
• Identify and digest the kind of amino acid combinations found in α-gliadin
• Not be digested or inactivated by the enzymes present in the human intestinal tract
• Work at the temperatures in the human body
• Have the potential to be mass-produced, by being made in a lab-grown bacterium
They found such an enzyme normally made by the acidophilic bacterium (Alicyclobacillus sendaiensis) called kumamolisin-As (or KumaWT).
They used computer modeling to figure out how to make this enzyme do everything it needed to do to help digest gluten for patients with celiac disease, and they were very successful. In a laboratory setting, KumaWT can break down over 95% of the parts of gluten that are toxic to people with celiac disease.
This is very interesting and exciting research. However, this enzyme has only been used in a laboratory setting and not even on lab animals. It will be a very long time before it is proved to be safe and effective in humans. Even if it is safe, and it can digest 95% of the gliadins, that would not be enough to prevent damage to the intestines of people with celiac disease. It might be enough to protect them against accidental exposure via gluten contamination of a food, and that in and of itself would be extremely helpful. People with celiac disease could eat at restaurants that have gluten-free selections without having to worry about whether or not they were 100% free of gluten.
Additionally, the use of computer methods to discover how to modify a bacterial enzyme for this specific purpose shows how effective computer modeling can be, and this type of research may yield even better results in finding treatments for celiac disease and other illnesses.