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Christian
Slater starred in a 2008 American TV
series
called, “My Own Worst Enemy.” Slater was
a
secret agent with a chip in his brain that allowed
his
employers to turn him from a mild mannered
family
man to a super spy without each knowing
of
the other’s existence. The showed last only nine
episodes;
apparently the drama was its own
worst
enemy.
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So it comes as no surprise that some scientists believe that
people are their own worst enemies when it comes to protecting their health. Good
intentions can have bad results. How might this relate to our topic of the past
few weeks, the benefits of disease and infection?
Some diseases have had a positive effect on survival in
specific conditions (like hemochromatosis and plague) and even how malarial fever can kill bacteria. This goes against the popular
idea that less disease is better, and that whatever we do to kill infectious
organisms is good. We try to be as sterile as possible; just look at what
surgeons do before entering the operating room. The health industry has given us
antibacterial soaps, cleaning products, plastics, cosmetics, toothpastes,
pencils, and even antibacterial computer keyboards!
The majority of these products use triclosan as the active ingredient. First
introduced as a pesticide in 1972, triclosan (chemical name:
2,4,4’-trichloro-2’-hydroxydiphenyl ether) is an antibacterial and antifungal
agent. Triclosan’s mechanism of action at low concentrations is to disrupt
fatty acid synthesis as a bacteriostatic
agent (slows bacterial growth and reproduction); at high levels it can
disrupt membranes and act as a biocidal
agent (kills organisms).
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Just
because something is an antibiotic, it doesn’t mean it
kills
bacteria. Many of the common antibiotics we use are
bacteriostatic,
meaning that they inhibit the growth. This
allows our immune
system time to overcome the intruder
on its own.
Bactericidal agents do actually kill the
bug, but they still need
help from the immune system. If
you took enough to
kill all the bacteria, you’d need a capsule
the size of a bus!
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Triclosan
can control bacterial contamination on hands and skin; hospital staff are encouraged
to bathe or shower in triclosan solutions to prevent the spread of MRSA
(pronounced “mersa” – methicillin resistant Staphylococcus
aureus) in hospital wards. However, this is for control of contamination,
not necessarily infection.
Triclosan has been proven effective in reducing infections
rates only in cases of gingivitis
(inflammation of the gums). However, a 2009 study stated that 75% of Americans over the age of
six years have detectable levels of triclosan in their urine. This is significant since there is emerging data that suggests that
triclosan might be harmful to people’s health.
High triclosan levels in urine and the environment mean high levels around
microorganisms as well. But this shouldn’t be bad – it is supposed to kill germs, isn’t it? Many scientists worry that high triclosan levels also promotes
bacterial evolution, selecting for the mutants that are resistant to the
chemical. We all have good reason to worry about this because it’s happened
before. Many bacteria, from MRSA to Mycobacterium
tuberculosis, to vancomycin-resistant enterococcus, are wreaking havoc
because we have fewer drugs that are effective against them.
In the laboratory, triclosan exposure has resulted in
resistant strains of E. coli, salmonella, and rhodospirillium, and other
organisms. Industry scientists argue that there is no data that triclosan
causes resistance to develop in the wild, but a 2011 EU report suggests that this very well may be
taking place; the levels of triclosan seen in people and the environment
are similar to the levels used to drive resistance in the laboratory.
The bacterial resistance mechanism at work might be more
dangerous than the resistance to triclosan itself. Several studies have deduced
that triclosan interacts with proteins in the bacterial multidrug efflux pump. Many
prokaryotes have this system; it works to pump non-bacterial small molecules,
including antibiotics and toxins, out of the cell.
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This
cartoon represents a model of the E. coli
multidrug
efflux pump. Protons pumped out are
allowed
back in, and this produces the force needed
to
pump out the drugs. This is another reason that
you
need your immune system to overcome a
bacterial
infection – the little buggers are working
against
you!
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Want more evidence? An August 2012 study showed that
triclosan has an immediate and dangerous affect on muscle activity. You remember your heart?- it’s
a muscle. In mice, triclosan exposure caused a 25% reduction in cardiac muscle
function, and an 18% reduction in mouse grip strength. An idea for your next
arm wrestling contest – wear a glove and slather it with liquid hand soap. You
now have an 18% better chance at winning….if you are competing against a mouse.
Triclosan also affects endocrine function. A new study indicates that
triclosan exposure in pregnant rats lowers mother, fetal, and neonatal
levels of thyroid hormone. Triclosan has a structure similar to a thyroid
hormone; it may trick the body into believing it has enough hormone. The
thyroid would then reduce the production of the hormone, leaving the system starved
of thyroid hormone. Most of this work has been done in amphibians, fish and
rats, but a similar affect on human thyroid function is predicted.
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Your
body is exposed to many antigens from many sources.
If
you are an only child or have parents that microwave
your
toys, you are exposed to many fewer antigens. Many
scientists
hypothesize that your immune system needs
these
exposures to balance your developing system
between
the Th1 responses and Th2 responses. Too much
Th2
and you will start to overreact to innocuous antigens –
allergies, asthma, and autoimmunity can result.
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Case in point - most everyone has an idea that food allergies
and asthma seem to be on the rise. The CDC stated in 2008 that there had been a 20% increase in food
allergies in the years between 1997 and 2007. In a large number of these cases,
children with food allergies also had eczema or skin allergies (27%) or
respiratory allergies (30%), compared to only 8-9% of kids without food
allergies. Basically, allergies are significantly on the rise, and if you have
one, you are much more likely to have more than one.
Importantly, the rise isn’t occurring everywhere. Rural
Africa - no increase in allergies or asthma. The arctic inuit peoples – very
little allergy or asthma despite high levels of childhood smoking. Farm kids in
just about every country – far lower levels of respiratory allergies, food
allergies, asthma, and autoimmune diseases.
The hygiene hypothesis states that a lack of immune stimulation when young leads to exuberant responses
to antigens that would normally be innocuous. Isn’t it interesting that the
increase in allergies and asthma also correlates with the onset of
antimicrobial agents being added to everything?
Different ideas abound as to how being clean might lead to
increased immune hypersensitivities. One hypothesis is that a lack of antigen
exposure in urban kids leads to a loss of balance between different T lymphocyte
responses (see picture above). Infections tend to stimulate Th1 responses. A too clean, urban
environment results in less stimulation of Th1 and therefore a relative over
stimulation of the Th2 response. Increased Th2 leads to the kinds of responses
seen in asthma and allergies. Indeed, atopic (allergy) patients do show an
increase in Th2-driven cytokines.
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Are
we too clean as a society? Maybe we can back off
on
the antimicrobial agents and spend more time in
the
woods and the park. A brisk hike is as good for
your
health as a spotless bathtub – and its more fun.
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Additionally, the exposure to bacteria, viruses and
parasites stimulates the immune regulatory system as well. Antigen presentation
can be stimulatory or suppressive; suppressive presentation leads to regulatory
(suppressive) lymphocyte production. It is hypothesized that regulatory
lymphocytes help to balance the Th1 and Th2 responses and reduce the incidence
of allergy.
We see that several portions of the immune system could be
involved in helping the natural environment fine tune our immune responses. But
what is it that induces this wonderful balance and state of good health?
A 2010 study suggested that the important molecule is something called
arabinogalactan. This is a ubiquitous polysaccharide made of arabinose and
galactose monomers. It is a component of many cell walls – bacterial, parasite,
worm, grasses and other plants, and is in farm (unprocessed) milk.
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Arabinogalactan
is present in cow’s milk, in the grasses
that
cows are fed, and in the dung patties that they leave
behind.
And they last as well – there is a cowshed in
Wales
that dates to 1402, making it the oldest building
in
Wales. Cowshed – uninterrupted immune stimulation
for
six centuries!
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Two final notes to bring this full circle. Triclosan use has
now been linked to higher rates of allergy. In particular, urinary triclosan levels correlate with development of food allergy.
Correlation does not equal cause and effect, but it does ask a question that
needs to be answered.
Lastly, increases in autism parallel increases in asthma and allergy, and a recent study shows that kids with autism and behavioral
fluctuations have less stimulation of
regulatory immune response after infection. Like allergy and asthma, autism definitely has a
genetic component, but could the hygiene hypothesis and autism be linked as well?
For
more information or classroom activities, see:
Anti-microbial
products –
Triclosan
and health –
Hygiene
hypothesis –
