1. 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

2. - Journal of Neuroimmunology, May 1, 1998
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.”

3. 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 Crohn’s Disease.”

4. “IN PURSUIT OF AUTOIMMUNE WORM CURE”
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 children’s feet, installed sewers and stopped using human waste as fertilizer, and the worms mostly disappeared.”

5. More from the Times article…
“But there may be a downside to all this hygiene. Children in industrialized countries, which are relatively worm-free, 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.”

6. “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.”

7. “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.”

8. 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.

9. YEAR BY YEAR, THE DATA GROWS…

10. 2000
“Does the Failure to Acquire Helminthic Parasites Predispose to Crohn’s Disease?”
Journal of The Federation of American Societies for Experimental Biology, Drs. Elliott, Urban, Argo and Weinstock

11. “Lymphocytes from inflamed intestine due to Crohn’s 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 Crohn’s disease, which is an overly active Th1 inflammation.”

12. - Trends in Immunology, Drs. Yazdanbakhsh, van den Biggelaar, Maizels
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 anti-parasite response, might benefit the host by blocking progression to atopic reactions.”

13. 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.”

14. - Current Opinion in Gastroenterology, Drs. Feillet, Bach
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.”

15. 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.”

16. - Gastroenterology, Drs. Summers, Elliott, Urban, Thompson, Weinstock
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.”

17. - Parasitology Research, Drs. Reddy and Fried
2006
The Use of Trichuris Suis and Other Helminth Therapies to Treat Crohn’s 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.”

18. Helminths as Governors of Immune-Mediated Inflammation
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 lifestyles…Loss of natural helminth exposure removes a previously universal Th2 and regulatory immune biasing imparted by these organisms….”

19. Porcine whip worms now available commercially!
October 19, 2007 – two friends me a link to this site:
– thank you, Stewart Johnson!
Porcine whip worms now available commercially!

21. The Increasing Incidence of Immune Regulatory Disorders
From Bach J-F., (2002) 347:

23. POOR SANITATION, IMPURE FOOD AND CROWDED LIVING CONDITIONS
Helminthic
infections
Regulatory T Cell
Conditioning
(Prevents)
Inhibits
Excess
Reactivity
Viral, bacterial
and protozoan
infections
Excess
Immune reactivity
Crohn’s disease
and other diseases
GENETIC PREDISPOSITION

24. 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; IL10 and TGF
(Kuroda, Parasite Immunol. 23:305)
This is important because helminths have an unique effect on the immune system. Helminths influence the immune system to respond in a Type 2 reaction. Helminths prevent strong Type 1 responses. Helminths are adapted to live in mammals. They are adapted to influence our immune systems so that they do not cause extreme tissue damaging responses. Helminths want to keep their host happy. The Type 2 response limits the number of helmniths. Helminths use the Type 2 response to prevent over whelming their host. Humans have always had helminths. Fosillized human feces (coproliths) from 10,000 years ago contain helminth eggs. Humans have adapted to helminths also. Our immune system “expects” that they will be present. Perhaps it is the lack of helminths that permits the immune system to develop excessive inflammatory reactions like IBD.

25. Helminths Modulate Immune Responses in People
Th2 response to tetanus toxoid
(Sabin, J. Infect. Dis. 173:269)
Children have reduced atopy
(Yazdanbakhsh, Science 296:490)
PBMC IL10 and TGF production
(Doetze, Int. Immuol. 12:623)
This is important because helminths have an unique effect on the immune system. Helminths influence the immune system to respond in a Type 2 reaction. Helminths prevent strong Type 1 responses. Helminths are adapted to live in mammals. They are adapted to influence our immune systems so that they do not cause extreme tissue damaging responses. Helminths want to keep their host happy. The Type 2 response limits the number of helmniths. Helminths use the Type 2 response to prevent over whelming their host. Humans have always had helminths. Fosillized human feces (coproliths) from 10,000 years ago contain helminth eggs. Humans have adapted to helminths also. Our immune system “expects” that they will be present. Perhaps it is the lack of helminths that permits the immune system to develop excessive inflammatory reactions like IBD.

26. Trichuris suis (Porcine whipworm)
Self-limited colonization
No multiplication in host
No direct transmission
The Iowa group uses Trichuris suis, the pig whipworm, because it has excellent saftey criteria. T. suis cannot be transmitted to other people. No diseases have ever been attributed to T. suis. We can isolate clean T. suis eggs! The Iowa group has treated about 100 patients with T. susis eggs and have not seen any adverse effects.
Eggs stable and easy to produce

27. Trichuris suis Therapyin
Active Ulcerative Colitis

28. Overall Response
No side effects, complications

29. Time to Response

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

31. Regulatory T Cells CD8 Treg TGFb IL10 Tr1 TGFb Th3 Th2 IL4, IL5
FoxP3
TGFb
CD25
Mostly CD4
IL10
TGFb
Tr1
IL10
TGFb
Th3
Th2
IL4, IL5
IL13, IL10

32. Prevent/reverse inflammation
No contact required
Helminths
TLR4
LPS
TGFb
CD4
Regulatory
T cells
CD4
CD8
IL10
Th2 cytokines
(IL4, IL13) @
IFNg
Th1
IL12 @
Th1 / Th2
Effector
T cells
T Cell
Proliferation

33. Judy Chinitz
New Star Nutritional Consulting
(914)
Allan Goldblatt
Autism Associates of New York
(516)