The Hygiene Hypothesis: Intestinal Parasites and Immune System Regulation

Judy Chinitz, M.S., M.S., New Star Nutritional Consulting Allan Goldblatt, P.A., Autism Associates of New York

The Year Was 1998

Dr. Sudhir Gupta had just published his paper, Th1- and Th2-like Cytokines in CD4+ and CD8+ Cells in Autism - Journal of Neuroimmunology, May 1, 1998

These data suggest that an imbalance of Th1- and Th2-like cytokines in autism may play a role in the pathogenesis of autism.

Also in 1998
Dr. Andrew Wakefield said, at his first Defeat Autism Now! conference, that the pathology he had found in the intestines of children with autism was a subtle variation on Crohns Disease.

NY Times, August 31, 1999

IN PURSUIT OF AUTOIMMUNE WORM CURE For most of Western history, the average child walked around with a bellyful of parasitic worms: pinworms, tapeworms, hookworms. Then modern civilization came along, put shoes on the childrens feet, installed sewers and stopped using human waste as fertilizer, and the worms mostly disappeared.

More from the Times article

But there may be a downside to all this hygiene. Children in industrialized countries, which are relatively wormfree, have a much greater tendency than those in other countries to grow into adults with autoimmune disorders (in which the body is attacked by its own immune system), like rheumatoid arthritis, multiple sclerosis, lupus and inflammatory bowel disease.

Recently, researchers at the University of Iowa gave a drink containing the eggs of half-inch-long parasitic worms to six people suffering from acute, chronic inflammatory bowel disease. Five went into remission and the sixth improved substantially.

He [Dr. Joel Weinstock] and his colleagues began wondering about worms called helminths, which have been with humans for thousands of years.Dr. Weinstock thinks inflammatory bowel diseases develop when the body overreacts to the normal bacteria in the digestive tract, unleashing a salvo of Th1 cells that end up damaging the colon and bowel themselves. Helminths, he says, trigger a Th2 response, which dampens the Th1 response.

Parasitic Worms and Inflammatory Diseases - Parasite Immunology, October, 2006 Drs. Zaccone, Fehervari, Phillips, Dunne, Cooke
Worm parasites have co-evolved with the mammalian immune system for many millions of years and during this time, they have developed extremely effective strategies to modulate and evade host defenses and so maintain their evolutionary fitness. It is therefore reasonable to conclude that the human immune system has been shaped by its relationship with parasitic worms and this may be a necessary requirement for maintaining our immunologicial health.

YEAR BY YEAR, THE DATA GROWS

2000
Does the Failure to Acquire Helminthic Parasites Predispose to Crohns Disease? Journal of The Federation of American Societies for Experimental Biology, Drs. Elliott, Urban, Argo and Weinstock

Lymphocytes from inflamed intestine due to Crohns disease secrete a Th1- pattern of cytokines.Helminths and their eggs probably are the most potent stimulators of mucosal Th2 responses. The Th2 response provoked by parasitic worms can modulate immune reactions to unrelated parasitic, bacterial and viral infections.Perhaps failure to acquire these parasites and experience mucosal Th2 conditioning predisposes to Crohns disease, which is an overly active Th1 inflammation.

2001
Th2 responses without atopy [allergy]: immunoregulation in chronic helminth infections and reduced allergic diseases - Trends in Immunology, Drs. Yazdanbakhsh, van den Biggelaar, Maizels It is suggested that down-regulatory immune mechanism, which dampen the antiparasite response, might benefit the host by blocking progression to atopic reactions.

2002
An Enteric Helminth Infection Protects Against an Allergic Response to Dietary Antigens - Journal of Immunology, Drs. Bashir, Andersen, Fuss, Shi, Nagler-Anderson

Our results demonstrate that, in a murine [rodent] model, helminth infection protects against the development of allergy.

2004
Increased Incidence of Inflammatory Bowel Disease: the price of the decline of Infectious Burden? - Current Opinion in Gastroenterology, Drs. Feillet, Bach
Converging clinical and experimental data strongly suggest the protective nonspecific role of infections on inflammatory bowel disease. The extension to inflammatory bowel disease of the hygiene hypothesis opens new therapeutic perspectives including the revisiting of probiotics and other forms of exposure to bacteria or parasite components.

ALSO IN 2004
Can Helminth Antigens be Exploited Therapeutically to Downregulate Pathological Th1 Responses? - Current Opinion in Investigational Drugs, Drs. Raine, Zaccone, Dunne,Cooke In developing countries where helminth infections are highly prevalent, Th1 autoimmune diseases are almost never reported.

2005
Trichuris Suis Therapy for Active Ulcerative Colitis: A Randomized Controlled Trial - Gastroenterology, Drs. Summers, Elliott, Urban, Thompson, Weinstock Conclusions: Ova therapy seems safe and effective in patients with active colitis.

2006
The Use of Trichuris Suis and Other Helminth Therapies to Treat Crohns Disease - Parasitology Research, Drs. Reddy and Fried GI nematodes [family of worms, including hook worm] are powerful modulators of the immune response, and as such, they may have the potential to affect the outcome of concurrent infections with other parasites, bacteria, or viruses.If harboring helminths protects against immune-mediated disease, then these animals must be viewed as useful animals that may produce important compounds helpful for therapy for human disease.

2007
Helminths as Governors of Immune-Mediated Inflammation - International Journal of Parasitology, Drs. Elliott, Summers, Weinstock
Immune-mediated diseases (e.g. inflammatory bowel disease, asthma, multiple sclerosis and autoimmune diabetes) are increasing in prevalence and emerge as populations adopt meticulously hygienic lifestylesLoss of natural helminth exposure removes a previously universal Th2 and regulatory immune biasing imparted by these organisms.

October 19, 2007 two friends email me a link to this site: www.autismtso.com thank you, Stewart Johnson!

Porcine whip worms now available commercially! www.ovamed.org

TheIncreasingIncidenceofImmuneRegulatoryDisorders
FromBachJF.,(2002)347:911920

POOR SANITATION, IMPURE FOOD AND CROWDED LIVING CONDITIONS

Viral, bacterial and protozoan infections Excess Immune reactivity

Helminthic infections Regulatory T Cell Conditioning Inhibits Excess Reactivity

Crohns disease (Prevents) and other diseases

GENETIC PREDISPOSITION

Helminths Modulate Immune Responses in Rodents

Modulate responses to unrelated Ag

(Kullberg, J. Immunol. 148:3264)

Delayed graft rejection

(Ledingham, Transplantation 61:184)

M-

TNF and IL12;

(Kuroda, Parasite Immunol. 23:305)

IL10 and TGF

Helminths Modulate Immune Responses in People

Th2 response to tetanus toxoid
(Sabin, J. Infect. Dis. 173:269)

Children have reduced atopy PBMC

(Yazdanbakhsh, Science 296:490)

IL10 and TGF production

(Doetze, Int. Immuol. 12:623)

Trichuris suis
(Porcine whipworm)
Self-limited colonization
No multiplication in host No direct transmission Eggs stable and easy to produce

Trichuris suis
in

Therapy

Active Ulcerative Colitis

Overall Response

~No side effects, complications

Time to Response

How do worms in the duodenum regulate the ileum and colon?

Regulatory T Cells

CD8
CD25

Treg
FoxP3

Tr1

Th3

Th2

TGF IL10
TGF

TGF
IL10

Mostly CD4

IL4, IL5 IL13, IL10

Helminths

Prevent/reverse inflammation No contact required

TLR4 CD4 Regulatory T cells CD4

LPS

Th2 cytokines (IL4, IL13) IL12 IFN

@

IL10

CD8 TGF

Th1

Th1 / Th2

T Cell Proliferation
@

Effector T cells

Judy Chinitz New Star Nutritional Consulting www.newstarnutrion.com (914) 244-3646 Allan Goldblatt Autism Associates of New York www.autismny.com (516) 921-3456