The Hygiene Hypothesis:  Intestinal Parasites and Immune

System Regulation

Judy Chinitz, M.S., M.S., New Star Nutritional ConsultingAllan 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 Crohn’s 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 children’s 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 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.”

“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 Crohn’s Disease?”

– Journal of The Federation of American Societies for

Experimental Biology, Drs. Elliott, Urban, Argo and

Weinstock

“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.”

2001Th2 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.”

2002An 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.”

2004Increased 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 2004Can 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.”

2006The 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.”

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….”

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

The Increasing Incidence of Immune Regulatory DisordersFrom Bach J-F., (2002) 347:911-920

Viral, bacterialand protozoan

infections

ExcessImmune reactivity

Crohn’s diseaseand other diseases

GENETIC PREDISPOSITION

POOR SANITATION, IMPURE FOOD AND CROWDED LIVING CONDITIONS

Helminthic infections

Regulatory T Cell Conditioning

(Prevents)

InhibitsExcess

Reactivity

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)

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)

Trichuris suis(Porcine whipworm)

• Self-limited colonization

• No multiplication in host

• No direct transmission

• Eggs stable and easy to produce

Trichuris suis Therapy

in

Active Ulcerative Colitis

Overall Response

~No side effects, complications

Time to Response

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

TregFoxP3

TGF

CD25

Mostly CD4

Regulatory T Cells

IL10TGF

Tr1

IL10

TGF

Th3 Th2

IL4, IL5IL13, IL10

CD8

Helminths

Prevent/reverse inflammationNo contact required

RegulatoryT cells

CD8

T CellProliferation

@

Th1 / Th2

EffectorT cells

CD4

IL10Th2 cytokines

(IL4, IL13)

@

IFN Th1

IL12

TLR4LPS

TGF

CD4

Judy ChinitzNew Star Nutritional Consultingwww.newstarnutrion.com(914) 244-3646

Allan GoldblattAutism Associates of New Yorkwww.autismny.com(516) 921-3456