We have all been taught that our bodies are made up of trillions of cells, each with its own unique makeup and function. But did you know that most of those cells are not the product of our own genetic code? They are microbial cells residing within the environment of the human body, and they outnumber our human cells tenfold.
There is no need to panic, however. As scientists are discovering, many of these “bugs” are not harmful at all, but provide valuable assistance to many vital functions. They are called “commensal” bacteria, meaning that they coexist with humans without causing harm. We start to accumulate our small friends from an early age. Although the amniotic sac is sterile, as soon as it breaks and we begin our journey through the birth canal, we pick up commensal cells from our mothers. Later, through exposure to the world via pets, family members, and the physical environment we crawl upon and put in our mouths as infants, we are gathering even more of these bacteria. These new inhabitants take up residence in a part of the body that suits their unique needs, and generally they provide significant benefit to their host.
As it turns out, recent studies show that children who grow up with dogs tend to have fewer respiratory infections than those children who do not. Another study showed that Amish and Swiss children who grew up on farms, helping with chores such as caring for pigs and milking cows, riding horses and consuming mostly raw milk were much less vulnerable to allergic reactions both respiratory and dermal. Other studies have linked exposure to our “dirty” natural world to be inversely correlated to a prevalence of allergies and auto-immune disorders.
All of these discoveries jive with the development of the “Hygiene Hypothesis”. This hypothesis, originally proposed in 1989 by David P. Strachan at St. George’s Hospital Medical School in London, postulates that without early exposure to many antigens, as is the case in our modern antiseptic world, certain T-cells, or white blood cells, do not get the “education”, or stimulation required to distinguish between self and non-self cells, thereby launching attacks on the human body’s own tissues while overreacting to antigens. When exposed adequately, T-regulator cells develop to down-regulate immune response in T-cells, helping to prevent autoimmune disorders and allergic responses.
We will focus primarily on how this hypothesis relates to inflammatory bowel disease, or IBD, and specifically Crohn’s disease and ulcerative colitis. One – 2 million people in the US are suffering from one of these autoimmune diseases today. Traditional therapy usually involves a combination of steroids and immune suppressants. These all can have devastating side-effects, especially when used long term, and are often limited in their effectiveness. When these methods fail, the last resort is often surgery to remove sections of the small intestine or colon. The incidence of these diseases is far greater in developed nations than in countries where exposure to certain parasites is common. The parasites in question are called helminths, or a worm-like creature generally found in warmer climates. There are many types, some which reside in specific areas of the human body, and several that are predominately hosted by wild or domestic animals. Studies looking at petrified human feces in caves as well as examination of ancient mummies have shown that helminths have inhabited the human gastrointestinal system for many thousands of years.
Dr. Joel Weinstock of Tufts Medical Center in Boston has been a leader in the study of helminths and their protective role in immunological diseases. He points to supporting data that demonstrated that Ethiopians infected with hookworm had a lower incidence of asthma, as borne out by an additional study carried out in Vietnam. Conversely, Gabonese children who were treated for their helminth infestations became susceptible to dust-mite allergy. Another study showed that an increase in frequency of multiple sclerosis, another autoimmune disease, correlated with a decrease in helminth exposure in developed nations. When multiple sclerosis patients were infected with helminths, they demonstrated fewer flare-ups and fewer new lesions, as shown on MRI, compared with a control group of uninfected patients. Some promising results have been seen in autism patients as well. These are just a few examples of research that has been carried out clearly linking helminth exposure with a reduction in autoimmune and allergic pathologies.
Dr. Weinstock has chosen to focus his studies on finding a treatment for Crohn’s and ulcerative colitis through the introduction of helminths into the gastrointestinal tract. After prior testing on rodents, studies are now commencing on humans. Weinstock points out that some helminths are uniquely adapted to a relationship with its given host, a relationship that has evolved over thousands of years of coexistence. The worms have adapted by developing some protective mechanisms so as to survive in a potentially hostile environment. In protecting themselves, the helminths have also caused a dampening action on some of our immune responses, which benefits us. Humans are also exposed to other worms particular to animals; through hunting, farming and other forms of domestication. Most of these worms do not colonize within the human host, and several do not pose any threat to our health.
It is by utilizing one of these worms, specifically Trichuris suis, a type of pig whipworm, that human studies are showing significant remission in Crohn’s and ulcerative colitis symptoms. Because the natural host of T. suis is the pig, it cannot survive for long in a human, nor can it reproduce. It does not leave the gut to infect other parts of the body or transfer to a secondary host.
How does it work?
First of all, the ova, or eggs of T.suis (see image below) are consumed orally in a briny solution. They are microscopic and have a hard shell that resists stomach acids. They attach to the mucosa, or mucous membrane, between the small and the large intestine. There, they hatch and release various substances which trigger immunological responses. The tiny larvae move into wrinkles, called crypts in the mucosa of the colon, wiggling around and stimulating blood circulation in the membranes. After about 2 weeks, any viable larvae have died off, and become digested like a protein. During a course of the dosage is repeated every 2 weeks for 20-24 weeks. Treatment can be repeated as needed to maintain a balanced system.
The worms balance an overactive immune system in several ways. The presence of the larvae stimulate mucous production, which forms a barrier to the lining of the gut, protecting it from inflammation. The helminths also release several chemicals that produce a T-cell regulating response so that an anti-inflammatory environment is created. These actions are probably the most significant, as they allow the T-regulators to regain their influence over the rampant inflammation produced by T-1 and T-2 cells by limiting function of the dendritic cells and macrophages that “present” the antigens to the T-cells. Helminths produce other immune-regulating substances as well, all in an effort to survive in the environment of the human gut. In doing so, they minimize the symptoms of an overreactive immune system and provide relief to us humans. While protecting their existence, they also protect their host.
Although treatment is already available in other parts of the world, the FDA has only recently approved T.suis studies in the US. It is the first time the agency has granted approval for whole organism therapy. A spokesperson for the FDA was even quoted as saying “ The FDA does recognize the potential importance of alternative therapies, including certain intestinal worms.”
Sometimes we must look backward to find the way forward. Here’s to future harmony between man and microbe!
The Ultimate Social Network
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Helminth–host immunological interactions: prevention and control of immune-mediated diseases
Annals of the New York Academy of Sciences
Volume 1247, Issue 1, January 2012, Pages: 83–96, David E. Elliott and Joel V. Weinstock
Amish children living in northern Indiana have a very low prevalence of allergic sensitization
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Volume 129, Issue 6 , Pages 1671-1673, June 2011
Mark Holbreich, Jon Genuneit, Juliane Weber, Charlotte Braun-Fahrländer, Marco Waser, Erika von Mutius.
Worms to the rescue: Can worm glycans protect from autoimmune diseases?
Volume 62, Issue 4, April 2010, Pages: 303–312, Loes M. Kuijk and Irma van Die
Article first published online : 25 JAN 2010, DOI: 10.1002/iub.30
Immunomodulators of Helminths:
Promising Therapeutics for Autoimmune Disorders and Allergic Diseases
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2010 25 (2) 109-110
Helminths and the IBD hygiene hypothesis
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Volume 15, Issue 1, January 2009, Pages: 128–133, Joel V. Weinstock and David E. Elliott
Parasites and the hygiene hypothesis
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10 November 2008 Dr. Kristen Kerksiek
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Documentation related to T. Suis treatment