Could Infecting People With Hookworms Help Treat Ulcerative Colitis Someday?

Could hookworm therapy be the next big thing for inflammatory bowel disease (IBD)?

While most people may originally balk at the idea of being infected with hookworm larvae, a new study indicated that hookworms could be a breakthrough treatment for individuals with ulcerative colitis and Crohn’s disease—the main types of IBD.

“Once it is explained that hookworms have co-evolved with the human body over millennia, how we think they work, and that they have no chance of replicating in the body, most people are very open to the idea,” Tom Mules, MBCHb, a physician at the Malaghan Institute of Medical Research and a lecturer at the University of Otago School of Medicine in New Zealand, told Health.

Mules co-led the new study, published in the journal Inflammatory Bowel Diseases, examining whether or not patients could tolerate hookworm therapy for IBD ulcerative colitis and Crohn’s disease, both of which are associated with chronic inflammation of the gastrointestinal tract.

In the study, the scientists observe that some people with IBD “already use medically unsupervised hookworm therapy, suggesting it may be of benefit.” But ultimately, evidence proving it works is lacking. 

Critically, the point of this research wasn’t to evaluate whether or not hookworm therapy works. Instead, scientists wanted to evaluate if it can be well-tolerated and safe.

This research indicates that the answer is yes and suggests it’s reasonable to move on to the next phase of research—a full-scale randomized control trial.

How Hookworm Therapy Could Help People With IBD

Scientists have started to notice a strange trend. People are increasingly diagnosed with IBD, and incidents in places where IBD was once rare are becoming more common.

Why this is occurring is not exactly clear, but researchers have proposed one curious reason: actions like improved sanitation mean people are infected with gastrointestinal parasites like hookworms less often.

Historically, people who live in countries where parasites are more common tend not to develop IBD. In turn, it’s possible that improved living standards—and fewer parasites—mean more IBD.

There have been a few previous studies looking at hookworm therapy for IBD, but these have included patients with Crohn’s disease and people who are still sick, and many had issues with their study design.

In one study of 56 Crohn’s disease patients, the authors did not find any benefits.

However, early research on mice suggests parasitic worms can help the gut outcompete the inflammation-producing bacteria that drive IBD. The parasites triggered mucus production, which supports a good type of bacteria called Clostridia. This resulted in a healthy balance of gut bacteria.

Other mice studies also suggest parasitic worms could work as a treatment for IBD because of how they influence inflammation.

Advantages of Hookworm Therapy Over Typical Treatment

In some cases, doctors might recommend people with ulcerative colitis undergo surgery, which involves removing the colon and the rectum.

This surgery is more commonly known as j-pouch surgery.

However, is it much more common for people to treat ulcerative colitis with medication, namely anti-inflammatory drugs used orally or topically. Most people respond well to medication, but people with more severe symptoms may see fewer benefits.

The study team views hookworm therapy as a potential alternative therapeutic option and sees it as something that could help people who have trouble adhering to daily medication.

“One of the key findings of this study was that a single dose of hookworm can reside in the body for several years, if not longer,” said Mules.

He described the process as “infect and forget”—after infection, the patient doesn’t need to adhere to any further steps.

Mules was inspired to examine this therapy because of the many patients he sees that want an alternative to conventional medicine.

“The more I learn about hookworm, such as its amazing lifecycle to reach the intestine, its ability to live in the body for years, and its symbiotic relationship with humans, the more I want to find out if, and how, it works to treat disease,” said Mules.

Raymond Cross, MD, a professor of medicine and the director of the IBD program at the University of Maryland School of Medicine, told Health that he has not seen a patient who has attempted hookworm therapy and thinks this might be rarer in the United States.

“However, as a provider that cares for patients with IBD, I have certainly observed patients experimenting with non-approved treatments to improve control of their disease,” said Cross.

Evaluating the Feasibility of Hookworm Therapy

The New Zealand-based research team evaluated 20 patients with ulcerative colitis in disease remission, the period during which symptoms of a disease are reduced or disappear.

At this point, the only treatment the participants were using was 5-aminosalicylic acid, an anti-inflammatory drug. 

The team focused on patients in disease remission because they think hookworm therapy is better suited to keeping a person in remission, rather than pushing them from an active disease state into remission.

The idea is that once in remission, hookworm therapy could prevent them from having disease flares and reduce the need to take medications. While in remission patients experience less pain and discomfort, but if they forget to take their medication, a flare-up can happen.

Study participants were randomly given a placebo or 30 hookworm larvae. The placebo was capsaicin cream—a pain reliever cream derived from chili peppers and described as giving “a similar sensation as hookworm larvae.”

Larvae or the cream was applied to a gauze and then placed on the participant’s forearm.

Mules explained that after the larvae were applied, they burrowed through the skin and entered the bloodstream, subsequently traveling to the lungs where they matured for a few weeks. Next, they migrated to the trachea, are swallowed, and entered the gastrointestinal tract. When they reach the small intestine they latch onto the mucosa, where they can live for years.

The group was monitored for 52 weeks and during this time they were asked about their IBD symptoms, their reaction to the intervention, and their well-being.

By the end, 40 percent of participants in the hookworm group and 50 percent of the participants in the placebo group maintained clinical remission.

Because of the small sample size, the team observed that “there was limited statistical precision to consider differences in clinical remission.”

“As this is a small study, it is possible that the study was not powered to detect a smaller difference in relapse rates, although I would argue that for a therapy like this, clinicians do not care about a small difference in relapse rates,” said Cross. “We want a therapy that is significantly better than the standard of care.”

The Side Effects of Hookworm Therapy

As expected, almost everyone in the hookworm group had detectable eggs in their feces at the end of the experiment. All of these participants also developed mild eosinophilia, which happens when the body produces a large amount of a type of white blood cell and is often a sign of a parasitic infection.

This group also experienced more nausea, abdominal pain, diarrhea, and rashes at the site of the application.

Mules described these as “very common adverse effects” of early hookworm infection. They are caused by the body’s immune response to being infected with a parasite.

All side effects resolved within ten weeks, with some much sooner, indicating that this type of therapy is safe. The intervention did not trigger a disease flare—something the study team was initially concerned about.

“They [the side effects] are generally mild and quickly settle as the hookworm and human enter their symbiotic relationship,” said Mules. “If you prepare people that these will occur, most do not need any treatment for the side effects.”

Waiting to See If Hookworm Therapy Is a Viable Treatment Option

What’s needed next is a large, randomized control trial that will examine the effectiveness of this intervention.

Because this takes time and money, it’s difficult to say when this will happen. But Mules and colleagues believe hookworm therapy has enough promise and potential advantages that the investment is worth it.

Another hindrance could be the possibility that people will be turned off by this type of therapy.

One of the reasons potential study participants gave for not wanting to take part was “being disciplined to undergo infection with hookworm.” But Mules does not see this being too much of an issue.

“It may not be for everyone,” he said, “but the fact that many people do it already suggests many are open to the idea.”