Saturday Evening Post

By Patrick Perry

Have efforts to cleanse and safeguard our environment and health inadvertently placed us at greater risk for certain diseases?

Some researchers believe so.

During the past 75 years, industrialized nations have increased hygiene and reduced exposure to various types of microorganisms. People left farms and migrated to urban areas, donned shoes, erected cement walkways, and structured the landscape to eliminate any environmental exposure to bacteria and microorganisms in the belief that all were harmful. Crohn's disease was first recognized in the Jewish populations of New York City in the 1930s but soon surfaced in other ethnic groups and countries around the world. Over time, scientists noted an increase in other disorders of the immune systems, including multiple sclerosis, allergies, and type 1 diabetes.

Looking for an explanation for the increase in IBD and other disorders, a team of researchers at the University of Iowa began to focus on what we may have left behind when we moved from rural communities to urban areas. By eliminating microorganisms that inhabited the human gut, did the human body become more vulnerable to immune reactions?

The team developed the IBD hygiene hypothesis, proposing that raising children in extremely hygienic environments may have had a negative impact on immune development, predisposing children to immunologic diseases like IBD. They also postulated that modern hygienic practices have led to significant reduction in exposure to certain helpful parasites called helminths, or worms, that help regulate host immune systems and prevent excessive inflammatory responses, which could underlie a mechanism of protection. Indeed, helminths boast broad immunoregulatory properties that evolved over the centuries into a successful host-parasite interaction.

One's initial impulse when thinking about "worms" is to get rid of them, but they perform a unique function in the human immune system. They help dampen the inflammatory immune response, specifically the type 1 T helper cell response, which reacts to bacteria or viruses that invade the bloodstream. The research group believes that eliminating worms may also eradicate one of the few environmental factors that help prevent IBD.

To test their hypothesis, the team decided to try worm therapy. Several years ago, the team treated severely ill IBD patients with the eggs of worms, specifically Trichuris suis (or pig whipworm), which is similar to the human whipworm. During the six-month study, five of the six patients went into remission that lasted between two to five months. On follow-up, patients were given the agent once every three weeks, and the team found that with this dosing schedule, they could maintain remission. People who were chronically ill for years went into complete remission--no diarrhea, no abdominal pain, no joint problems.

The University of Iowa team began conducting further double-blind studies of helminthic (worm) therapy for patients with Crohn's disease and ulcerative colitis with further success. To learn more about current research and ongoing trials of this hopeful treatment for IBD, the Post spoke with gastroenterologist Dr. Joel Weinstock, professor of medicine and director of the division of gastroenterology and Center for Digestive Diseases at the University of Iowa, who is spearheading the therapy.

Post: Could you tell us about your ongoing study of helminth (worm) therapy for patients with inflammatory bowel disease?

Weinstock: When talking about inflammatory bowel disease (IBD), I am referring to ulcerative colitis and Crohn's disease. Both are inflammatory conditions of the intestine that typically begin when people are in their teens or 20s.

People with IBD experience recurring, chronic symptoms that include diarrhea, abdominal pain and blood loss through the gastrointestinal (GI) tract, among other problems that result from inflammation of the intestinal tract, and these symptoms can persist for years.

IBD seems to be on the increase. While once very rare to see a patient with Crohn's disease or ulcerative colitis, today it is extremely common.

Although the diseases have probably been with us for some time, they were not recognized until the mid-1930s. Other diseases are following the same pattern. For instance, multiple sclerosis seems to be of modern derivation.

Post: Why are these diseases on the increase?

Weinstock: We think that immunological diseases are on the rise due to lifestyle.

In the late 1990s, my colleagues and I considered possible causes of Crohn's disease. While we sifted through the data, one thing that impressed us was that these are diseases with a geographical preference and are increasing in frequency.

For instance, IBD is known to have a North-South gradient. Crohn's disease is common in the North and rare in the South of the United States, and the same is true in Europe. Worms fare better in warmer climates, so people who live in the South are more apt to have worms than people in the North. While prominent 50 years ago, these gradients are disappearing. IBD, for example, is increasing in frequency in Japan, South Korea, and wherever the quality of life and living standards are improving.

Today, IBD is estimated to affect about one in every 250 people in some regions of the United States. At one time, the disease affected about one in 5,000 Americans, so the incidence is increasing. While we are now living better, longer, and cleaner, we are getting a new category of disease, one that is not the same disease of old.

Post: What are helminths?

Weinstock: We have been studying organisms known as helminths, worm-like organisms that live In the GI tract. When you go to the bathroom, you excrete waste that is about 50 percent live bacteria. You are teeming with life. And this life within is important for helping you digest food, toning the immune system, and producing vitamins. You need gut "flora," or bacteria. If you lose intestinal flora, you won't be healthy. As a species, we evolved with intestinal flora. Humans and other animals have coexisted with helminths since the dawn of time. When you think about it, you are talking about millions of years of coevolution. These organisms need us to survive; otherwise, they become extinct.

In the real world, almost everyone had worms. They are very common in children, who get worms when exposed to contaminated soil and by swallowing the eggs. At least one third of the people around the world today have worms in their GI tract.

Post: When did this begin to change?

Weinstock: In the 1930s, we started deworming everyone. We did it directly by giving people antiworming agents and indirectly through sanitation. Kids used to run around barefoot. Some forms of helminths you pick up through skin. If you drink out of a well or stream, you can pick them up. Now we wear shoes and have water filtration systems, so our water is very clean. The same is true with food. Today, food is much cleaner than it was 70 years ago, so children aren't getting these worms.

Post: As a result of deworming our environment, are we now at greater risk for certain diseases?

Weinstock: In the U.S. and industrialized countries, worms are no longer part of the GI tract. There is a direct inverse relationship between worms and immunological diseases. People who have worms don't tend to get immunological diseases, while people without worms do. This coincidental association led us to hypothesize that perhaps worms are a protective factor and that deworming was not a good Idea.

Worms are also protective because they stimulate aspects of our system that help to dampen hyperreactive immune systems. Minus worms, Immune systems tend to react much faster and may lead the human body to overproduce powerful substances that lead to excessive inflammation of the intestinal tract. Deworming results in a hyperactive immune system. This is a known fact.

This process of deworming may be one of the factors leading to the expansion and emergence of a variety of immunological diseases, such as childhood asthma, that are very common in the United States and England. In many less developed countries, asthma is infrequent.

Another example is hay fever. In some countries, this disease is rare--zero. But perhaps 20 to 25 percent of the American population has to live in air conditioning and can't go outside at certain times of the year. That Is not the normal state of affairs. While we learn to live with it, It isn't right.

To make a long story short, we have shown what intestinal worms can do to dampen the Immune system, and how they work. In clinical studies, we actually gave worms to people with IBD, with very good results.

Post: Do most people in the U.S. still carry worms, and how would one know?

Weinstock: Most people don't carry them; you can tell if people have helminths. But not everybody without helminths will get an immunological disease. Luck, genetics, and certain other triggers must be present for the disease to emerge. But if you have helminths, we believe that you will be less likely to get IBD because you have protective factors. A virus, for example, is less likely to trigger the disease in someone with helminths.

Post: How do you introduce worms into patients?

Weinstock: Every two weeks, patients consume a few ounces of a liquid to which are added microscopic eggs, but you cannot see anything in the drink.

We use a worm that is extremely safe and stays in people's systems for a very short time. It is almost invisible, so you can't tell you have them.

There have been no recognizable side effects, and this worm cannot be transmitted to anyone around you.

Post: What do the helminths do inside the intestinal tract?

Weinstock: They hatch out of the eggs, grow into small organisms, then the immune system of the host reacts to these organisms and eventually gets rid of them. The interaction between worms and the human immune system triggers the regulatory pathways that down-modulate the inflammation that dampens the inflammatory response. They are turned off.

Post: How long have you sustained a remission in patients?

Weinstock: In some patients, we have sustained remission beyond four years. Remember, we are not talking about 100 percent of people with IBD. We are talking about a subset of patients; some don't respond; some respond, then relapse a year later; while other patients respond and stay responsive--they don't get sick again.

Post: Do responsive patients have both a genetic susceptibility and an absence of helminths?

Weinstock: Not necessarily. That would imply that helminths are essential. But disease could break out in people who have worms. You must think of two issues--prevention and treatment. Once a disease is established, it is hard to reverse--the proverbial horse is out of the barn. And getting the horse back in the barn becomes harder. Treatment may help.

Children exposed to worms and these organisms growing up may be much less prone to developing ulcerative colitis, Crohn's, multiple sclerosis, hay fever, allergies, and other diseases. But once the diseases develop, you have to convert an aberrant immune system into one that is more normal, which is more difficult to do.

Post: Are people in remission also still on anti-inflammatories or other IBD-type medications?

Weinstock: We always try to taper them off of other immunomedicines or get them down to a minimal dose. The most successful patients have been able to get off of more dangerous agents.

Post: How do people overcome any initial hesitation of swallowing worms?

Weinstock: Patients in the trial are not afraid. Given the choice of taking medications like the steroid prednisone and the immunosuppressant Imuran for years with all the unpleasant side effects, or swallowing some harmless eggs every two weeks with no side effects, which path would you take? The therapy is not as yet perfected. We are at the very beginning of what we hope will be a breakthrough.

Post: This new approach sounds very promising and hopeful for patients with IBD.

Weinstock: We now have important clinical data suggesting that the idea is correct. Nothing is absolute in science, however. This organism resides in pigs--about 20 percent of pig herds carry the worms. Farmers who raise pigs may be exposed to the organism. It is a well-recognized observation that people who are raised near big animals are less likely to get asthma or immunological diseases. Perhaps exposure to animal worms is one of the reasons.

Post: What has been the reaction of fellow gastroenterologists?

Weinstock: Originally, we had lovers and haters, as one would expect of any new theory. Right now, it is becoming much more widely accepted. In the next couple of years, you will hear a lot about it.

The real value of an agent could take years of testing. How many it will help, for how long, whether it might actually cure some people or become a supplement remains to be seen. Much work still needs to be done.

Using a treatment regimen of worms, doctors at the University of Iowa are helping patients with Crohn's disease and ulcerative colitis. Dr. Joel Weinstock and his team have found that patients who swallow a mixture of the helminth or parasitic worms suspended in Gatorade achieve relief and remission from IBD. Every few weeks, patients return to the clinic to repeat the treatment: if they do not, symptoms return.

The worm research is an extreme example of a field known as probiotics: the use of living organisms to treat diseases of the gastrointestinal tract and other organs.

Probiotics--Some physicians recommend probiotics to patients suffering from intestinal disease. Probiotics are beneficial bacteria, such as Lactobacillus acidophilus and Bifidobacterium bifidum, that support digestive health by inhibiting the growth of harmful bacteria, promoting good digestion, boosting immune function, and increasing resistance to infection. Beneficial bacteria present in fermented dairy foods--namely live culture yogurt--have been used as a folk remedy for thousands of years. Yogurt is the traditional source of beneficial bacteria, but brands of yogurt can vary in their bacteria strain and potency. Good-quality supplements in powder, liquid extract, capsule, or tablet form offer consumers other sources of probiotics.