The Journal Of Allergy and Clinical Immunology have published a report which reported that Australia researchers are looking into a treatment strategy for celiac disease which involves hookworms. Twelve adult people suffering from clinically diagnosed celiac disease were infected with hookworm and gluten was then reintroduced slowly back into their diet. After 52 weeks, the eight participants who saw the trial out were able to tolerate up to 3kg of gluten without any signs of gluten toxicity. This is equivalent to eating two slices of bread or a medium-sized bowl of spaghetti with no ill effects. Their gluten tolerance increased by a factor of 60, a massive change, and all eight chose to keep the hookworm when the trial ended.
Usually, if these participants ingested gluten it would cause a massive inflammatory response resulting in them suffering symptoms like diarrhea, cramps, and vomiting. So have these results revealed the potential for these Hookworm parasites and their secretions to treat a range of inflammatory diseases?
The research team attributed their results to a protein found in hookworms with the ability to keep the human immune response in check. It is thought that a particular protein, found in the hookworm secretions, can be used to develop a treatment for inflammatory conditions, such as celiac disease, inflammatory bowel disease (IBD) and asthma. Inflammatory diseases have one thing in common and that is an imbalance in certain T cell functionality, which results in overwhelming inflammatory processes. Researchers have shown that that hookworms can change T cells from being pro-inflammatory to being anti-inflammatory.
The Australian scientists who successfully regulated the inflammatory response in celiac patients by infecting them with hookworms in the trial discussed above are now collaborating with a major pharmaceutical company to develop a treatment for inflammatory bowel disease (IBD), based on proteins secreted by the worms.
It is ironical that a protein secreted by hookworms which themselves can cause such devastating disease can be used as a healing agent. Although helminthic therapy showed promising results in treating these 8 people with celiac disease, it is an unconventional form of immunotherapy that involved deliberately infecting patients with hookworm which is a parasitic worm with serious health implications of its own. So if the protein responsible for the results can be identified and isolated and mass produced into a tablet, many people suffering from celiac disease and other inflammatory diseases may get the much-anticipated relief they have hope for.
What are Hookworm?
Hookworm infection affects over half a billion people globally. It is a leading cause of maternal and child morbidity in the developing countries of the tropics and subtropics. In developed countries, hookworm infection is rarely fatal, but anemia can be significant in a heavily infected individual. Symptoms include itching and a localized rash at the site of infection when the hookworm larvae penetrate the skin. A person with a light infection may have no symptoms. A person with a heavy infection may experience abdominal pain, diarrhea, loss of appetite, weight loss, fatigue, swollen stomach, anemia and both protein and iron deficiency. Coughing, chest pain, wheezing, and fever will sometimes result from severe infection
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Hookworm Ova
Hookworm infection is caused by small roundworms known as helminths. Two species of hookworms commonly infect humans: Ancylostoma duodenale and Necator americans. Hookworm infection is a soil-transmitted helminthiasis. Humans are infected when the soil is contaminated with faeces infected with hookworm ova (eggs). The eggs thrive in warm sandy or loamy soil where temperatures are over 18 °C and in areas where rainfall averages more than 1000 mm (40 inches). When both these conditions exist the eggs eventually hatch into rhabditiform larvae (1-2 days). which then develop into
infective filariform larvae in a
matter of 1-2 weeks.
Adult Hookworm
The infective larvae penetrate through the soft skin of the foot when a person walks barefooted in the contaminated soil. Once inside the body, the larvae migrate through the vascular and lymphatic systems and eventually reach the lungs where they develop for a 1-2 weeks. From the lung, they travel up the trachea where they are coughed up and are swallowed. They then pass down the esophagus and enter the digestive system, finishing their life-cycle in the intestine where the larvae mature into adult worms. It is here where hookworm does their most damage, the worms hook on to the intestinal wall and suck blood. The adult worms mate and the female lays many thousands of eggs per day which are excreted in the faeces and the cycle starts again when unsanitary conditions allow the faeces to contaminate soil.
The mouth of a Hookworm
The entire life-cycle of hookworm takes about 5–7 weeks, i.e. for adult worms to mature, mate and produce eggs. Without treatment, Necator causes a prolonged infection. Generally, they can survive for about 1–5 years. On the other hand, Ancylostoma adults are short-lived, surviving on average for only about 6 months.
The Hygiene Theory
People have co-existed with parasites all throughout history. Parasites have evolved sophisticated strategies to avoid attack by their human host’s immune system. At the same time, the human immune system developed strategies to deal these parasitic worms. The inflammatory response against the worm evolved so that it did not have a detrimental effect on the human host tissues. This co-evolution has forced us to “tolerate” worms to a point where exposure to these parasites, as well as other infectious and commensal microorganisms, is critical for shaping the normal development and function of our immune system.
However, during the past century urbanisation, improved sanitation and health care improvements in the developed world have reduced our exposure to many infectious diseases, including parasitic worms such as hookworm. Due to this, the number of allergic and autoimmune inflammatory disorders have risen dramatically. These disorders arise when the immune system, which evolved to fight infections caused by viruses, bacteria or parasites, incorrectly reacts to harmless stimuli such as environmental factors, food and the body’s own tissues.
One theory to explain the rise in inflammatory disorders such as celiac disease is that children growing up in a "clean world" are no longer exposed to "dirt" microorganisms which activate our immune system. This lack of exposure causes our immune system to develop improperly, leading to inflammatory diseases such as asthma, inflammatory bowel diseases and autoimmune diseases such as multiple sclerosis and celiac disease.
This hygiene theory is supported by a number of epidemiological and observational studies in human populations. Studies, where worm-infected children from developing countries were treated with drugs to cure their parasite, developed more allergic skin reactivity, whereas children who were not treated remained allergy-free.
This fact led to the Australian study which proved that hookworm infestation reduced inflammation in celiac patients and allowed them to consume more gluten without any side effects.
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