Transcript The Hygiene Hypothesis: Intestinal Parasites and Immune

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 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 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 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.”
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 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 Disorders
From Bach J-F., (2002) 347:911-920
POOR SANITATION, IMPURE FOOD
AND CROWDED LIVING CONDITIONS
Viral, bacterial
and protozoan
infections
Excess
Immune reactivity
Helminthic
infections
Regulatory T Cell
Conditioning
Crohn’s disease (Prevents)
and other diseases
GENETIC PREDISPOSITION
Inhibits
Excess
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?
Regulatory T Cells
CD8
CD25
Treg
Tr1
Th3
Th2
IL10
TGF
TGF
IL10
IL4, IL5
IL13, IL10
FoxP3
TGF
Mostly CD4
Prevent/reverse inflammation
No contact required
Helminths
TLR4
CD4
Th2 cytokines
(IL4, IL13)
IL12
IFNg
IL10
Th1
Regulatory
T cells
LPS
CD4
CD8
TGF
Th1 / Th2
Effector
T cells
T Cell
Proliferation
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