In addition to its antiviral properties, Chlorella also has
antiinflammatory properties similar to a bacterial product called PSA
and I wonder if Chlorella contains PSA or a similar molecule. Helminths
stimulate IL-10 and IL-10, in turn, stimulates regulatory T-cells which
protect against autoimmunity.
http://www.eurekalert.org/pub
releases/2008-05/hms-ibp052208.php
Intestinal bacteria promote -- and prevent! -- inflammatory bowel disease
BOSTON, Mass. (May 28, 2008)Scientists search for drug candidates in
some very unlikely places. Not only do they churn out synthetic
compounds in industrial-scale laboratories, but they also scour coral
reefs and scrape tree bark in the hope of stumbling upon an unsuspecting
molecule that just might turn into next yearıs big block buster. But one
region that scientists have not been searching is their guts. Literally.
Now, a team of researchers at Harvard Medical School, Brigham and
Womenıs Hospital, and the California Institute of Technology have
demonstrated that a molecule produced by bacteria in the gutıs
intestinal microflora can eliminate symptoms of inflammatory bowel
disease (IBD), a condition that includes Crohnıs disease and ulcerative
colitis, in animal models.
³Given the sheer number of bacteria in the gut, the potential for
discovering new molecules that can treat a whole range of these diseases
is promising,² says Dennis Kasper, co-lead author on the study,
professor of medicine and microbiology and molecular genetics at Harvard
Medical School, and director of the Channing Laboratory at Brigham and
Womenıs Hospital.
The study will appear as the cover story in the May 29 issue of Nature.
Scientists have known for many decades that the mammalian gut is an
ecosystem teeming with approximately 1,000 different species of
bacteria, species as distinct from the host as a single-cell amoeba in
pond s***. Rather than causing disease, these bacteria are responsible
for protecting against infection and aiding digestion. An increasing
number of scientists also suspect that recent increases in asthma and
even certain food allergies are caused by disruptions in the delicate
balance of this intestinal ecosystem.
In 2005, Kasper and Sarkis Mazmanian, then a postdoc in Kasperıs lab and
now an assistant professor of biology at the California Institute of
Technology, discovered that a species of intestinal bacteria called
Bacteroides fragilis could restore immune system balance in mice that
were bred to lack intestinal bacteria. A particular product of B.
fragilis, a sugar molecule called polysaccharide A (PSA), recovered the
equilibrium of a certain subclass of immune system cells (called Th1 and
Th2) whose levels became skewed when bacteria in the gut were absent.
The researchers referred to PSA as a ³symbiosis factor,² one that
established a beneficial link between bacteria and mammals. This was the
first study in which such a link was demonstrated.
Interestingly, when the study was completed, Kasper and Mazmanian found
in these mice an abundance of immune system cells that were known to
protect against colitis and Crohnıs disease. In the current re****t, the
groups decided to expand these findings and explore potential links
between PSA and inflammatory bowel disease.
When immunocompromised mice with a specific pathogen-free microbiota
were given an intestinal bacterium called Helicobacter hepaticus, they
soon developed ³rip roaring² IBD, according to Kasper. However, when
Helicobacter was combined with B. fragilis, the mice were fine. Further
experiments revealed that PSAthe special sugar moleculewas the key
factor in preventing IBD. In fact, when mice were given Helicobacter
combined with PSA purified from B. fragilis bacteria, they showed no
symptoms of IBD.
³But then the key question was, if PSA was essential for preventing
these animals from coming down with either colitis or Crohnıs, how did
it do it"² says Kasper. ³What was the mechanism"²
The answer came by studying a subset of interleukins, that is, molecules
secreted by immune cells.
Previous studies had shown that two particular interleukins, called
IL-17 and IL-23, promote intestinal inflammation and are present at high
levels in IBD patients. Here, while the researchers found IL-17 and
IL-23 in the guts of animals who had received Heliobacter alone, these
interleukins were absent from animals who had also received both
PSA-producing B. fragilis and purified PSA.
³We realized that something in PSA must be preventing the inflammation
that causes colitis and Crohnıs, which would explain the reduction in
IL-17 and IL-23,² says Kasper.
This hunch brought the researchers to consider a third interleukin,
IL-10. The opposite of IL-17 and IL-23, IL-10 is anti-inflammatory and
had previously been shown to protect against experimental colitis.
The researchers once again administered Helicobacter and PSA-active B.
fragilis (the combination that had previously led to healthy mice), only
this time they included an antibody that blocked IL-10. As a result, the
mice all came down with IBD.
³This demonstrated for us the mechanism by which PSA protects against
IBD,² says Kasper.
Indeed, the researchers deduced that PSA prompts immune system cells to
secrete IL-10, which in turn suppresses the inflammation caused by IBD.
In other words, PSA is an anti-inflammatory.
This research should encourage people (including many scientists) to
consider the vast potential for beneficial contributions to human health
by ³good² bacteria. And whatıs more, ³This is the first time that a
beneficial molecule produced by intestinal bacteria has been shown to
work therapeutically in an animal model,² says Mazmanian.
The researchers caution that these findings do not promise any near-
term treatments for IBD. ³PSA might do the same thing in humans, and it
might not,² says Kasper.
However, the mechanism that theyıve discovered should persuade
scientists and drug manufacturers to consider new sources for expanding
the drug pipeline.
³There is currently no effort to develop molecules that are naturally
made by bacteria to use therapeutically,² continues Mazmanian. ³This
study opens up that possibility.²
--
Nature. 2008 May 29;453(7195):620-5.
A microbial symbiosis factor prevents intestinal inflammatory disease.
Mazmanian SK, Round JL, Kasper DL.
Division of Biology, California Institute of Technology, Pasadena,
California 91125, USA.
Humans are colonized by multitudes of commensal organisms representing
members of five of the six kingdoms of life; however, our
gastrointestinal tract provides residence to both beneficial and
potentially pathogenic microorganisms. Imbalances in the composition of
the bacterial microbiota, known as dysbiosis, are postulated to be a
major factor in human disorders such as inflammatory bowel disease. We
re****t here that the prominent human symbiont Bacteroides fragilis
protects animals from experimental colitis induced by Helicobacter
hepaticus, a commensal bacterium with pathogenic potential. This
beneficial activity requires a single microbial molecule (polysaccharide
A, PSA). In animals harbouring B. fragilis not expressing PSA, H.
hepaticus colonization leads to disease and pro-inflammatory cytokine
production in colonic tissues. Purified PSA administered to animals is
required to suppress pro-inflammatory interleukin-17 production by
intestinal immune cells and also inhibits in vitro reactions in cell
cultures. Furthermore, PSA protects from inflammatory disease through a
functional requirement for interleukin-10-producing CD4+ T cells. These
results show that molecules of the bacterial microbiota can mediate the
critical balance between health and disease. Harnessing the
immunomodulatory capacity of symbiosis factors such as PSA might
potentially provide therapeutics for human inflammatory disorders on the
basis of entirely novel biological principles.
Publication Types:
* Research Sup****t, N.I.H., Extramural
* Research Sup****t, Non-U.S. Gov't
PMID: 18509436
Planta Med. 2007 Jul;73(8):762-8. Epub 2007 Jul 5.
Stimulation of cytokine production in human peripheral blood mononuclear
cells by an aqueous Chlorella extract.
Ewart HS, Bloch O, Girouard GS, Kralovec J, Barrow CJ, Ben-Yehudah G,
Suarez ER, Rapo****t MJ.
Ocean Nutrition Canada Ltd., Dartmouth, NS, Canada.
CPE is an aqueous extract of the edible micro alga Chlorella
pyrenoidosa, which has been shown to have immunostimulatory effects in
vivo. In the present study, CPE was evaluated for an ability to
stimulate cytokine production by human peripheral blood mononuclear
cells (PBMC). PBMC from healthy individuals were treated ex vivo for 24
hours with 1, 10 and 100 microg/mL CPE. This resulted in a marked
increase in the level of IL-10, a regulatory cytokine, and strong
stimulation of the T-helper-1 (Th1) cell cytokines, IFN-gamma and
TNF-alpha. In contrast, stimulation of representative T-helper-2 (Th2)
cell cytokines, IL-4 and IL-13, was minor. CPE (1, 10 or 100 microg/mL)
did not cause a proliferation of human PBMC suggesting that enhanced
secretion of cytokines was not secondary to an increase in cell number.
We conclude that CPE stimulation of human PBMC induces a Th1-patterned
cytokine response and a strong anti-inflammatory regulatory cytokine
response, observations that await confirmation in vivo.
Publication Types:
* Research Sup****t, Non-U.S. Gov't
PMID: 17611933
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