Take 2,500 worm eggs and call me in the morning? Sounds more like a scene from Fear Factor than reputable medical advice, but if a small band of researchers is right, this just might be your prescription.
One member of that band is Linda Mansfield, VMD, PhD, a parasitologist in the College of Veterinary Medicine at MSU. She is optimistic about the prospect of using worms or worm products to treat inflammatory bowel disease (IBD) in people and thinks MSU is uniquely placed to play a significant role in this development.
Why anyone would think that worms are good for you is a story in itself. Getting rid of worms is generally thought of as a good thing that goes along with the high standard of living in wealthy, developed countries.
Instead, some researchers argue, it’s the improved hygiene in these societies that may account for IBD and a whole range of autoimmune disorders. According to this “hygiene hypothesis,” our immune systems require exposure to infections of all sorts early in life in order to develop sufficiently or appropriately.
Intriguingly, IBD, which has two forms – Crohn’s disease and ulcerative colitis – is virtually unknown in the developing world, while it is increasing dramatically in developed societies. When people from developing countries move to developed ones, their incidence of IBD increases. Is it possible that modern medicine and hygiene, while protecting people from virulent diseases, have eliminated exposure to microorganisms that are important to balanced health?
Over millennia, our immune systems evolved in environments where we were constantly exposed to bacteria, viruses, worms, and all sorts of microorganisms. In that time, we co-evolved ways to exist peacefully with each other and even to grow dependent upon each other.
After all, the successful parasite doesn’t want to kill its host; it wants a long-term relationship. In order to do that, it must exert some sort of brake on the host’s ability to eliminate it and, even better, offer the host some benefit.
“We know from past research that intracellular pathogens like viruses and bacteria elicit an immune response in the host that causes inflammation, but that worm parasites mount an anti-inflammatory defense that modulates inflammation,” Mansfield says. “The greater the worm burden, the greater the anti-inflammatory effect.
“It’s possible that the human immune system developed in a way that is dependent on parasitic worms to regulate immune responses,” Mansfield says. “When we eliminate worms, we lose their modulating effects.”
Dr. Joel Weinstock, previously at Iowa State, now at Tufts University, has shown in several dramatic studies of people with either Crohn’s disease or ulcerative colitis that having them drink a concoction of 2,500 pig whipworm (Trichuris suis) eggs mixed with Gatorade caused a short-term infection of their gastrointestinal tracts that was correlated with a significant reduction or remission of their IBD symptoms. The infection was short term because T. suis is the whipworm that infects pigs, not humans, so it cannot take hold. It also caused no side effects.
His first studies were on just a few people, but they have been replicated on increasingly larger groups and verified in double-blind studies. T. suis helped people with IBD so much that they begged to continue with the treatments after the original clinical trial safety study was completed.
The goal now is to identify the precise mechanisms by which this anti-inflammatory effect happens. Are there specific worm products that create it, or must the whole worm be present? When the immune system is not properly modulated, what are the microorganisms in the gut that cause problems? Are certain bacteria in our intestines always associated with excessive inflammation? Are these bacteria producing the disease, or are they instead the result of it? Mansfield thinks that MSU researchers have a good chance of answering these questions.
She has developed a mouse model of IBD that is initiated when the mice ingest the foodborne pathogen Campylobacter. This model can be used to study the effects of different treatments for IBD. And she has the expertise and resources of MSU’s Center for Microbial Ecology (CME) close by.
The CME has been funded by the National Science Foundation since 1989 to develop what is now a huge database that helps to identify and classify bacteria. Initially, researchers used this database to identify bacteria in soil for a variety of purposes. As most of the bacteria present in soil are also present in the intestine, this database can be a real asset for studies of human diseases of the gastrointestinal tract.
Taking a fecal or a biopsy sample from the mouse with IBD, the researchers can match the genetic “fingerprint” from the bacteria that are present to the fingerprints of bacteria that are in the database.
“There are many problems with identifying the harmful bacteria, and there are hundreds in the mix,” Mansfield says. “A typical way to identify bacteria is to culture them, but many of the bacteria in the gut are not able to be cultured. This method of identifying them through their genetic sequences will help tremendously in looking for associations. Even a single sample could give insights into the complex mix of bacteria that are present.”
Mansfield is enthusiastic about the application of this work to a wide variety of auto-immune conditions, such as asthma, diabetes, and multiple sclerosis. Some researchers suggest that all of these problems may be explained as combinations of the hygiene hypothesis and an individual’s genetic makeup.
In June 2006, the National Institutes of Health awarded Mansfield a five-year grant totaling more than $500,000 to conduct a project that will work to identify new molecules and compounds from the whipworm parasite that could be used as oral treatments for patients with IBD. Linda Chadderdon, MSU College of Veterinary Medicine