PART I-->Dick Gallo - Hygiene Hypothesis (hh)-->Th2 <-- plus a bunch more (human holobionts) = EnteroTypes
randall
hi
part II to this post is here:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/msg/e17e23259cf4cbf1
OK i just said in this post:
Wed, 11 May 2011 13:40:00 -0700 (PDT)
Subject: Microbiome and ROS --> Small Intestinal (LMW-PTP and SHP-2)
Trick or TREAT? --> NF-kB -- ABSTRACTS --SFB theory<--- By RANDALL -
mercola & Byron Richards links
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/msg/9447ef0984f87bea
[....] Hey i'll do the ____hygiene hypothesis___ by ucsd's ___dick
gallo___ right after
this salient gut post.
Just so you KNOW what or which card your dealt is MOST imPortant.
<snip>
OK... so i keeP my WORD:
Richard Gallo (UCSD & LL37 fame) chimed in on hh in the UT.
http://www.signonsandiego.com/news/2011/jan/31/the-good-the-bad-and-the-ugly/
The hygiene hypothesis (hh)
It suggests lack of early exposure to infectious agents can suppress
development of the immune system
By Dr. Richard L. Gallo
Monday, January 31, 2011 at 12:01 a.m.
In 1998, researchers at the University of Georgia published a paper
that estimated about 5 million trillion bacterial cells reside on
Earth. That’s a 5 with 30 zeros. That’s a lot of bacteria. Indeed, if
each individual bacterium were a penny piled atop one another, it
would take a trillion light-years to reach the end of the stack, which
is far beyond the observable universe.
5,000,000,000,000,000,000,000,000,000,000 is that it? count em?
Some of these bacteria, Louis Pasteur and others duly discovered,
cause disease, and so contemporary humans have long been urged,
explicitly and otherwise, to fight back: Wash often. Stay clean. And
don’t skimp on those alcohol-based hand-sanitizing gels, foams and
lotions that reportedly kill 99 percent of all germs. Odds are there’s
a dispenser near you right now.
But is cleanliness really next to goodliness?
Maybe not. There is compelling, growing evidence that being too clean
might actually be bad for your health; that it results in increased
sickness and the development of chronic immunological ailments that
might not occur if we all dialed back on the Dial and dispensers.
This thinking is encapsulated in an idea called “the hygiene
hypothesis,” which first emerged in the late-1980s. The hypothesis
suggests that a lack of early childhood exposure to infectious agents
and microorganisms (not just bacteria, but viruses and fungi, too)
suppresses natural development of the immune system, resulting in
increased susceptibility to infection and disease.
The hypothesis has been used to help explain why allergies like hay
fever are less common in children from large families, even though
presumably these kids are exposed to more infectious agents than those
in smaller families. Epidemiologists have also noted that ailments
like asthma and eczema (a kind of skin inflammation) are more
prevalent in industrialized countries where personal cleanliness is
emphasized.
Though not conclusively proved, the hypothesis makes sense — at least
as part of a larger explanation. Let’s look at the science.
One’s a crowd
If the world is fraught with bacteria, so too are you. Based solely on
the average number of cells in a typical human being, we’re all more
inhuman than human. Bacterial cells outnumber human cells 10 to 1.
Your gut, for example, is a well-known bacterial repository, home to
hundreds of trillions of individual microbes (somewhere between 300
and 1,000 species), many of which beneficially assist in necessary
functions like digestion and immune response. Plus, they take up space
that might otherwise be occupied by nastier, disease-causing
pathogens.
Your skin is similarly populated. Recent studies have identified
hundreds of species, many previously unknown. One estimate calculates
the total number of skin-based bacteria on the average person at
roughly 1,000,000,000,000. These bacteria live in colonies, each
favoring a different environmental niche. The bacteria that prefer the
crook of your elbow, for example, are different from those
homesteading your forearm.
Swathed in our cloaks of microbial invisibility, some questions are
nonetheless obvious: How do skin bacteria survive our constant
assaults with soaps and antibiotics? And why don’t they make us sick
more often?
In research published this year and last, my colleagues and I
uncovered some of the answers. Our skin hums with constant
communication and interaction between commensal or benign bacteria and
skin cells. Certain species of superabundant Staphylococcus bacteria,
for example, produce a molecule that inhibits the inflammation
response (heat, redness, swelling) generated when you injure your
skin. That’s a good thing. Some inflammation is vital to healing, but
too much can be worse than the infection.
Why do Staphylococci do this? It’s hard to know for sure, but one
possibility is that it’s an evolutionary adaptation, a neat trick
bacteria have developed to reduce the chances that an inflammatory
response will kill them. Another possibility is that we have evolved
together and count on these bacteria to help us control the skin
response. In return for this microbial good deed, we reward specific
bacteria with a comfortable place to live.
Recently, we discovered that a specific type of Staphylococci —
Staphylococcus epidermidis, the most common bacterial species cultured
from human skin — produces antimicrobial molecules that kill some
other kinds of bacteria, including its cousin, S. aureus, a more
problematic bug that causes everything from pimples and boils to
deadly pneumonia, meningitis and sepsis.
S. epidermidis not only makes antimicrobials, it also instructs human
skin cells to make natural antimicrobials of their own, thus serving
as both warning system and mentor. The result is a balanced
relationship that benefits both human hosts and our commensal
bacterial buddies.
Scorched skin policy
Overuse of antibiotic soaps and hand sanitizers upsets this happy
homeostasis by essentially killing all bacteria, good and bad. The
consequence of this scorched skin policy is that we kill the germs
that sometimes contaminate our skin and make disease transmission more
difficult, but also reduce the effectiveness of our skin’s
antimicrobial defenses.
Wiping out all microbes means your skin is wide open to recolonization
by all comers — commensals and pathogens. It may be a tossup which
returns first and faster. Excessive cleanliness also removes natural
oils that help keep skin supple and intact. Dry skin is more prone to
cracking, which provides new entry points for bacteria and other
agents. Some bacterial species that are harmless resting atop your
skin are troublemakers inside it.
Of course, no one’s suggesting we abandon antimicrobial soaps, gels
and lotions. In some situations and circumstances, such as hospitals
and health care, they are essential. Every effort must be made to
reduce exposure to pathogens. More broadly, people should continue to
wash their hands regularly and diligently. (There’s an ongoing debate
about whether daily washing beyond the wrists is necessary, but that’s
a different story.)
As always, nature suggests a solution, albeit one that first requires
us to more fully understand the complicated relationships between
microbes and our health. Rather than regularly render our skin a sort
of microbial dead zone, we could develop soaps and sanitizers that are
more discriminating or which include ingredients that promote the
return of bacteria like S. epidermidis or deter the development of
conditions like eczema. We do a little bit of that now with soaps and
lotions that contain compounds designed to help skin retain its oils
and moisture.
Someday you might slather up with something that selectively kills and
fertilizes, encouraging certain microbial species to take root and
call you home, thus restoring balance to our natural ecology.
i
Richard L. Gallo, M.D., Ph.D., is a professor of medicine and
pediatrics and chief of UC San Diego’s Division of Dermatology and the
dermatology section of the Veterans Affairs San Diego Healthcare
System
<sniP>
--------------
63 results for hygiene hypothesis - P NG:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=hygiene+hypothesis
Same 63 by date (most recent first = chrono order):
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&q=hygiene+hypothesis&start=0&scoring=d&hl=en&
What does HH do exactly in the context of your SKIN?
Makes Th2 atopic dermatitis is my answer.
OK so how does it do THAT?
Sugar sugar honey honey?
Let's see:
1381 hits for hygiene hypothesis - pubmed:
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=hygiene+hypothesis
#1 of these 1381:
http://www.ncbi.nlm.nih.gov/pubmed/21265804
Biochem Soc Trans. 2011 Jan 19;39(1):360-4.
Glycomarkers in parasitic infections and allergy.
Hoffmann-Sommergruber K, Paschinger K, Wilson IB.
*Institut für Pathophysiologie und Allergieforschung, Medizinische
Universität Wien, 1090 Wien, Austria.
Abstract
Both helminth infections and contact with allergens result in
development of a Th2 type of immune response in the affected
individual. In this context, the hygiene hypothesis suggests that
reduced prevalence of parasitic infections and successful vaccination
strategies are causative for an increase of allergies in
industrialized countries. It is therefore of interest to study glycans
and their role as immunogenic structures in both parasitic infections
and allergies. In the present paper we review information on the
different types of glycan structure present in proteins from plant and
animal food, insect venom and helminth parasites, and their role as
diagnostic markers. In addition, the application of these glycan
structures as immunomodulators in novel immunotherapeutic strategies
is discussed.
PMID: 21265804
YeP it's glyco ville and Th2 on or in YOU.
Glycans are evil LYCANs for teens to be scarred or mom & dad to fight
the allergy?
Nope.
http://en.wikipedia.org/wiki/Glycan
The term glycan refers to a polysaccharide or oligosaccharide. Glycans
usually consist solely of O-glycosidic linkages of monosaccharides.
For example, cellulose is a glycan (or, to be more specific, a glucan)
composed of beta-1,4-linked D-glucose, and chitin is a glycan composed
of beta-1,4-linked N-acetyl-D-glucosamine. Glycans can be homo- or
heteropolymers of monosaccharide residues, and can be linear or
branched. Glycan may also be used to refer to the carbohydrate portion
of a glycoconjugate, such as a glycoprotein, glycolipid, or a
proteoglycan.
http://en.wikipedia.org/wiki/Glycan#Assembly
In eukaryotes, N-linked glycans are derived from a core 14-sugar unit
assembled in the cytoplasm and endoplasmic reticulum. First, two N-
acetyl glucosamine residues are attached to dolichol phosphate, a
lipid, on the external side of the endoplasmic reticulum membrane.
Five mannose residues are then added to this structure. At this point,
the partially finished core glycan is flipped across the endoplasmic
reticulum membrane, so that it is now located within the reticular
lumen. Assembly then continues within the endoplasmic reticulum, with
the addition of four more mannose residues. Finally, three glucose
residues are added to this structure. Following full assembly, the
glycan is transferred en bloc by the glycosyltransferase
oligosaccharyltransferase to a nascent peptide chain, within the
reticular lumen. This core structure of N-linked glycans, thus,
consists of 14 residues (3 glucose, 9 mannose, and 2 N-
acetylglucosamine).
Image: http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=glyco.figgrp.469
Dark squares are N-acetyl-glucosamine; light circles are mannose; dark
triangles are glucose.
<snip>
99 hits- hygiene hypothesis autoimmun* - pubmed:
http://www.ncbi.nlm.nih.gov/pubmed?term=hygiene%20hypothesis%20autoimmun*
Here's one (#6 of 99) for IBD'ers
The GUT stinks (dysbiosis) from the oral cavity on DOWN?
In a HH way or every day?
Just to SAY:
http://www.ncbi.nlm.nih.gov/pubmed/20458622
The role of oral hygiene in inflammatory bowel disease.
[...] CONCLUSIONS: These findings suggest that oral hygiene practices
may cause alterations in the flora of the oral mucosa, which causes
imbalance in the gut microbiome (dysbiosis), and thereby contributes
to the pathogenesis of IBD. Conversely, the increased frequency of
dental problems in IBD patients might be due, at least in part, to
alterations in oral flora or to their disease.
PMID: 20458622
#4 of 99 looks interesting:
http://www.ncbi.nlm.nih.gov/pubmed/20628601
PLoS One. 2010 Jul 7;5(7):e11484.
Systemic Toll-like receptor stimulation suppresses experimental
allergic asthma and autoimmune diabetes in NOD mice.
Aumeunier A, Grela F, Ramadan A, Pham Van L, Bardel E, Gomez Alcala A,
Jeannin P, Akira S, Bach JF, Thieblemont N.
Université Paris Descartes, Paris, France.
Abstract
BACKGROUND: Infections may be associated with exacerbation of allergic
and autoimmune diseases. Paradoxically, epidemiological and
experimental data have shown that some microorganisms can also prevent
these pathologies. This observation is at the origin of the hygiene
hypothesis according to which the decline of infections in western
countries is at the origin of the increased incidence of both Th1-
mediated autoimmune diseases and Th2-mediated allergic diseases over
the last decades. We have tested whether Toll-like receptor (TLR)
stimulation can recapitulate the protective effect of infectious
agents on allergy and autoimmunity.
METHODS AND FINDINGS: Here, we performed a systematic study of the
disease-modifying effects of a set of natural or synthetic TLR
agonists using two experimental models, ovalbumin (OVA)-induced asthma
and spontaneous autoimmune diabetes, presenting the same genetic
background of the non obese diabetic mouse (NOD) that is highly
susceptible to both pathologies. In the same models, we also
investigated the effect of probiotics. Additionally, we examined the
effect of the genetic invalidation of MyD88 on the development of
allergic asthma and spontaneous diabetes. We demonstrate that multiple
TLR agonists prevent from both allergy and autoimmunity when
administered parenterally. Probiotics which stimulate TLRs also
protect from these two diseases. The physiological relevance of these
findings is further suggested by the major acceleration of OVA-induced
asthma in MyD88 invalidated mice. Our results strongly indicate that
the TLR-mediated effects involve immunoregulatory cytokines such as
interleukin (IL)-10 and transforming growth factor (TGF)-beta and
different subsets of regulatory T cells, notably CD4+CD25+FoxP3+ T
cells for TLR4 agonists and NKT cells for TLR3 agonists.
CONCLUSIONS/SIGNIFICANCE: These observations demonstrate that systemic
administration of TLR ligands can suppress both allergic and
autoimmune responses. They provide a plausible explanation for the
hygiene hypothesis. They also open new therapeutic perspectives for
the prevention of these pathologies
pmid: 20628601
free text - full
http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20628601/?tool=pubmed
===============
Abstracts-----> psor and more:
The SUN (RAH) and UVB immunosuPPresion:
http://www.ncbi.nlm.nih.gov/pubmed/21271993
Br J Dermatol. 2011 Feb;164(2):344-355. doi: 10.1111/j.
1365-2133.2010.10149.x.
Sun exposure induces rapid immunological changes in skin and
peripheral blood in patients with psoriasis.
Søyland E, Heier I, Rodríguez-Gallego C, Mollnes TE, Johansen FE,
Holven KB, Halvorsen B, Aukrust P, Jahnsen FL, de la Rosa Carrillo D,
Krogstad AL, Nenseter MS.
Section for Climate Therapy, Department of Rheumatology, Oslo
University Hospital, Oslo, Norway LIIPAT, Centre for Immune
Regulation, Institute of Pathology, University of Oslo,
Sognsvannsveien 20, N-0027 Oslo, Norway and Oslo University Hospital,
Oslo, Norway Department of Pediatrics, Oslo University Hospital, Oslo,
Norway Department of Immunology, Dr Negrín University Hospital, Las
Palmas de Gran Canaria, Spain Institute of Immunology, Oslo University
Hospital, Oslo, Norway Faculty of Medicine, University of Oslo, Norway
Institute for Basic Medical Sciences, Department of Nutrition,
University of Oslo, Oslo, Norway Research Institute for Internal
Medicine, Oslo University Hospital, Oslo, Norway Section of Clinical
Immunology and Infectious Diseases, Oslo University Hospital, Oslo,
Norway Department of Pathology, Oslo University Hospital, Oslo, Norway
Department of Dermatology, Oslo University Hospital, Oslo, Norway
Lipid Clinic, Oslo University Hospital, Oslo, Norway.
Abstract
Background Ultraviolet (UV) radiation has immunosuppressive effects
and heliotherapy is a well-described treatment modality for psoriasis.
Objectives To characterize early sun-induced immunological changes
both local and systemic in patients with psoriasis. Methods Twenty
patients with moderate to severe psoriasis were subjected to
controlled sun exposure on Gran Canaria, Canary Islands, Spain.
Psoriasis Area and Severity Index (PASI) scores were evaluated. Skin
biopsies were obtained from lesional and nonlesional skin in 10
patients at baseline and on day 16 and from five additional patients
on day 2. Specimens were examined with immunohistochemistry and
polymerase chain reaction. Blood samples were obtained from all
patients at the same time points and were examined for T-cell subsets
and cytokine production. Results Significant clinical improvement was
achieved during the study period. CD4+ and CD8+ T cells in lesional
skin were significantly reduced in both the epidermis and dermis. In
contrast, dermal FOXP3+ T cells were relatively increased. In the
peripheral blood skin homing cutaneous lymphocyte-associated antigen
(CLA)+ T cells were significantly decreased after only 1 day in the
sun and in vitro stimulated peripheral blood mononuclear cells
demonstrated reduced capacity to secrete cytokines after 16 days.
Conclusions Our data show that clinical improvement of psoriasis
following sun exposure is preceded by a rapid reduction in local and
systemic inflammatory markers, strongly suggesting that immune
modulation mediated the observed clinical effect. We cannot completely
rule out that other mechanisms, such as stress reduction, may
contribute, but it is extensively documented that UV irradiation is a
potent inducer of immunosuppression and we therefore conclude that the
observed effect was primarily due to sun exposure.
PMID: 21271993
-------------
Arch Dermatol Res. 2011 Jan 29.
Increased expression of TRAIL and its death receptors DR4 and DR5 in
plaque psoriasis.
Peternel S, Prpić-Massari L, Manestar-Blažić T, Brajac I, Kaštelan M.
Department of Dermatovenerology, Clinical Hospital Center Rijeka,
University of Rijeka, Rijeka, Croatia, pete...@medri.hr.
Abstract
TNF-related apoptosis-inducing ligand (TRAIL) is recognized as an
important regulator of immune responses during infections and various
autoimmune-mediated pathologies. Its role in inflammatory dermatoses
is largely unknown. We aimed to investigate the expression of TRAIL
and its receptors DR4 and DR5 in psoriasis vulgaris.
Immunohistochemistry for TRAIL, DR4 and DR5 was performed on samples
of lesional (n = 10) and non-lesional (n = 10) skin of patients with
plaque psoriasis and skin of healthy volunteers (n = 10). Expression
of TRAIL and its receptors was further examined by means of double
immunofluorescence staining and co-localization with CD4, CD8, CD11c,
CD68, CD16 and CD56 markers. Immunohistochemical staining for TRAIL
was significantly enhanced in psoriatic lesional as well as non-
lesional epidermis compared to the epidermis of healthy skin. Lesional
epidermis also showed increased immunoreactivity for DR5. In addition,
expression of TRAIL and both of its receptors was significantly
increased in the dermis of lesional skin. As evidenced by double
immunofluorescence, TRAIL was readily expressed by most of the
examined cells of the inflammatory infiltrate in psoriatic lesions. In
contrast, the expression of DR4 was found mostly among CD4+ and CD8+
cells but was only nuclear, while DR5 showed cytoplasmic staining in
rare CD16+, CD56+ and CD68+ cells. According to abundant in situ
presence of TRAIL and its receptors in lesional psoriatic skin, it
seems that this cytokine participates in the complex interplay between
keratinocytes and cells of the dermal infiltrate and thus contributes
to the inflammatory cycle in psoriasis vulgaris.
PMID: 21279373
-----
No maguro in this sushi roll?
NoPe
http://www.ncbi.nlm.nih.gov/pubmed/21277746
J Dermatol Sci. 2011 Jan 11.
Circulating microRNA associated with TNF-α signaling pathway in
patients with plaque psoriasis.
Oyama R, Jinnin M, Kakimoto A, Kanemaru H, Ichihara A, Fujisawa A,
Honda N, Masuguchi S, Fukushima S, Maruo K, Ihn H.
Department of Dermatology and Plastic Surgery, Faculty of Life
Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, Japan.
PMID: 21277746
Does this microRNA look like halofuginone?
I'm gonna block that Psor right outa my LIfE. lol
--------------
Here's a cure for autoimmune conditions. STAT cut out the STAT3 GENE?
Really?
http://www.ncbi.nlm.nih.gov/pubmed/21278738
Nat Immunol. 2011 Jan 30.
Opposing regulation of the locus encoding IL-17 through direct,
reciprocal actions of STAT3 and STAT5.
Yang XP, Ghoreschi K, Steward-Tharp SM, Rodriguez-Canales J, Zhu J,
Grainger JR, Hirahara K, Sun HW, Wei L, Vahedi G, Kanno Y, O'Shea JJ,
Laurence A.
Molecular Immunology and Inflammation Branch, National Institute of
Arthritis, Musculoskeletal and Skin Diseases, National Institutes of
Health, Bethesda, Maryland, USA.
Abstract
Interleukin 2 (IL-2), a cytokine linked to human autoimmune disease,
limits IL-17 production. Here we found that deletion of the gene
encoding the transcription factor STAT3 in T cells abrogated IL-17
production and attenuated autoimmunity associated with IL-2
deficiency. Whereas STAT3 induced IL-17 and the transcription factor
RORγt and inhibited the transcription factor Foxp3, IL-2 inhibited
IL-17 independently of Foxp3 and RORγt. STAT3 and STAT5 bound to
multiple common sites across the locus encoding IL-17. The induction
of STAT5 binding by IL-2 was associated with less binding of STAT3 at
these sites and the inhibition of associated active epigenetic marks.
'Titration' of the relative activation of STAT3 and STAT5 modulated
the specification of cells to the IL-17-producing helper T cell
(T(H)17 cell) subset. Thus, the balance rather than the absolute
magnitude of these signals determined the propensity of cells to make
a key inflammatory cytokine.
PMID: 21278738
If balance is all we need then how come politics don't work better
instead of being so BITTER? LOL
OK, gut balance is due to clostridia and SFB inside of YOU.
Segmented Filamentous Bacterium inducts Th17 and prevents TREGs from
turning off inflammation.
So with a little L. plantarum now and then you keep the sFB in check
and stay WELL.
Swell...
I know...
It's like a giant SNOW BALL and your the guy or gal who shakes it
UP> LOL
==============
look for part II
here:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/msg/e17e23259cf4cbf1
randall.... don't you love living as LONG as you can with high quality
of LIFE? i do... see part II