When Overzealous Immune System is to Blame... Worms?

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    Whether worms that inhabit the gut can help control the immune overreaction in inflammatory bowel disease is being explored

    Poor sanitation, unclean water and contaminated food blight the lives of millions of people in the developing world. At the other end of the spectrum, too much cleanliness can also, it appears, prove troublesome.

    After millions of years of evolution together, humans have become accustomed to various microorganisms and worms that have for ages lived in and on them.

    The lack of contact with such organisms as a result of modern hygiene is being suggested as one of the reasons for the rise of various chronic inflammatory conditions in the developed world and perhaps increasingly in developing countries too.

    The ‘old friends'

    It seems that some organisms that co-evolved with humans had to be tolerated by the immune system, observed Graham A.W. Rook of the Windeyer Institute for Medical Sciences in London. These ‘old friends' have a role in setting the regulatory mechanisms within the immune system.

    Without such regulation, the human immune system attacks things it should not attack — trivial allergens in allergic diseases, self in autoimmune diseases and gut contents in inflammatory bowel disease, he noted in an email.

    Scientists and doctors are exploring whether worms that inhabit the gut can help control the immune overreaction that occurs during inflammatory bowel disease (IBD) and, if so, how those beneficial effects take place.

    A study recently published in the journal Science Translational Medicine looked at a man with the condition who infected himself with worms to overcome his health problems.

    IBD is a lifelong disorder where some part of the digestive tract becomes chronically inflamed. In ulcerative colitis, the inflammation occurs in the large intestine. In the case of Crohn's disease, however, the inflammation can affect any part of the digestive tract.

    The symptoms

    Sufferers can experience diarrhoea, bleeding, pain and fever when the disease is active, interspersed with periods of remission.

    “The exact cause of IBD is not known but is related to protective immune cells that are present in the lining of the intestines,” according to an article on the web site of the American College of Gastroenterology.

    This immune system can be triggered by an infection, something in the diet or environmental factors. But in people afflicted by the disease, the immune system did not turn off once this initial trigger was eliminated, leading to uncontrolled inflammation and attack on normal intestinal cells.

    IBD is common in industrialised countries and rare in developing regions of the world, observed Joel Weinstock and others in a journal paper. The reason for this difference has not been not explained, but the high rate of worm colonisation in less developed countries could be a protective factor. Dr. Weinstock, who is currently at Tufts University in the U.S., has pioneered research on worm therapy.

    As countries develop economically, IBD in the population increases, he noted in a publication with David Elliott last year. Modern hygiene and regulated food industries in developed countries had eliminated the pathways by which worms colonised humans. The worms released specific molecules to alter the immune responses of their human hosts.

    Moreover, studies published in the 1990s have shown that the children of South Asian immigrants to Britain had a significantly greater risk of developing IBD than the indigenous European population. In a paper published a few years back, T.V. Rajan of the University of Connecticut Health Center in the U.S. remarked that children of Indian parents who are raised in environmentally hygienic Western societies appeared to be highly prone to IBD.

    With rising incomes and better hygiene, it is possible that a similar dynamic could be at work in India too.

    “There is a feeling that perhaps inflammatory bowel disease is becoming more common in India,” said B.S. Ramakrishna of the Christian Medical College Hospital in Vellore, who also heads the Indian Society of Gastroenterology's Task Force on IBD. But there was no data on this due to a lack of good community-level studies, he remarked.

    According to him, there is a perception among specialists that IBD is more prevalent in the wealthier sections of Indian society than among the poor.

    Laboratory studies with mice have indicated that worms could play a beneficial role in colitis as well as a number of other inflammatory conditions and allergies.

    A few human trials have also taken place.

    In two trials carried out by Dr. Weinstock and others, the pig whipworm (Trichuris suis) was tested on people with ulcerative colitis and Crohn's disease. Both trials produced favourable results.

    In a paper that appeared recently in Science Translational Medicine, P'ng Loke of the New York University Langone Medical Center and others spoke of a 35-year-old man with ulcerative colitis. Faced with the option of surgery or immune-suppression therapy, he chose to infect himself with the eggs of the human whipworm (Trichuris trichiura).

    Dramatic improvement

    His condition improved dramatically and he remained in remission for almost three years. When a flare-up occurred, he took swallowed more worm eggs, which once again led to his symptoms subsiding.

    Dr. Loke and his colleagues examined a series of blood and tissue samples from the man. “Our main finding is that the worms might be restoring mucus production in his gut,” he told The Hindu. This seemed to be linked to the presence of more immune cells that made the protein interleukin-22.

    “This individual took a very big risk” using a worm that infected humans, he remarked. He hoped that the studies carried out on the man would lead to identification of parasite-derived molecules that made those beneficial effects possible. Speci
     
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