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Probiotics - Intestinal bacteria
The genomeceutical effect of probiotics and their potential role in
quenching autoimmune diseases and disorders of inflammation:
Probiotics are living microorganisms, which when ingested or locally
applied in sufficient numbers, confer one or more specified demonstrated
functional or health benefits for the consumer (EFFCA, European Food and Feed
Culture Association, 2003). Probiotics are also referred to as the "friendly,"
"beneficial," or "good" bacteria which when ingested act to maintain a healthy
intestinal tract and help fight illness and disease. Genomeceuticals are
natural ingredients (in this case, probiotics), which can beneficially affect
gene expression. Our group has spent decades studying the various health
aspects of probiotics. We realized that there is probably a direct correlation
between the intestinal flora and health of the human organism with regards to
potential autoimmune diseases and disorders of inflammation. In this paper, we
will discuss the immunomodulatory effects of probiotics, specifically their
role in down-regulating certain immune responses. We propose the use of
probiotics to quench the immune system under certain conditions, as well as a
mechanism by which such beneficial modulation may be achieved.
Introduction
More than 400 species of bacteria naturally
reside in the digestive tract. The bacteria function to break down food,
freeing nutrients for absorption. Many vitamins and essential amino acids are
only absorbed after being broken down by gut microorganisms. The proper balance
of good bacteria prevents detrimental organisms from invading the gut and
leaving the gastrointestinal (GI) tract susceptible to ailments. (1) The
consumption of probiotics in cultured milk products, such as yogurt, has been a
daily part of the Japanese and European healthy diet for many decades.
As far back as recorded history, communities have embraced certain foods
for their believed healing powers beyond basic nourishment. For instance,
fermented dairy products have been used for centuries to prevent and/or treat
common intestinal problems. Two different probiotics, Lactobacillus and
Bifidobacteria, are present in high numbers in fermented dairy products,
including yogurt and keifer, and are generally associated with the most
probiotic activity. For generations, people have consumed these foods to
improve the balance of beneficial microorganisms in the gut and enhance their
immune function.
How They Work
The exact mechanism by which probiotics function
in the gastrointestinal (GI) tract is not fully understood. However, they are
believed to confer health benefits by at least one of the following mechanisms:
competitive exclusion of enteric pathogens, neutralization of dietary
carcinogens, production of antimicrobial metabolites, and modulation of mucosal
immune responses.
The proper balance between good and bad bacteria largely determines the
health of the gut and as we are learning, the organism as a whole. Probiotics
may help prevent an imbalance in which too many harmful bacteria reside in the
digestive tract. A growing body of evidence has emerged confirming the positive
effect and potential of probiotics in humans. Recent research has implicated
probiotics in the treatment of other diseases, including atopic eczema, autism,
cancer, and food allergies. (2) However, to date, the vast majority of studies
have focused on the defense and integrity of the intestinal flora and the
immune system.
Probiotics may (not necessary for all benefits) take up residence in the
body and neutralize the effects of offending bacteria. They colonize the
exterior surface of cells in the GI tract and prevent potentially detrimental
pathogenic organisms from proliferation. Probiotics also produce components
shown to hinder the growth of certain types of harmful bacteria, as well as
lowering the risk for altered metabolic activity.
Strong scientific evidence supports the effects of probiotics on the
immune system, providing irrefutable evidence that certain probiotic strains
play a role in modulating both nonspecific and specific host immune responses.
Nonspecific, or innate, immune responses are a host's first line of defense.
Natural killer cells and phagocytes, residing in the peripheral blood and
tissues, are the major cellular effectors of nonspecific immunity. Natural
killer cells effectively fight off viruses, whereas phagocytic cells protect
against microbial infections. Both produce a variety of compounds that can
destroy both invasive materials as well as normal tissues.
Specific immune responses can be separated into two categories: humoral
immunity, and cell-mediated immunity. In the humoral immune response B
lymphocytes synthesize specific immunoglobulin molecules, or antibodies, that
are excreted from the cell and bind to the invading substance. In the cellular
immune response, T lymphocytes, bearing immunoglobulin-like molecules on their
surfaces, recognize and kill foreign or aberrant cells. T cells can be divided
into 2 subtypes based on their cytokine profile, Th1 and Th2. Th1 cells are
essential to cell-mediated immunity and produce IL-2, IFN-[gamma] and tumor
necrosis factor [alpha] (TNF-[alpha]). The main products of Th2 are IL-4, IL-5,
and IL-10 and are associated with humoral immunity and allergic responses.
Innate Immunity
Dietary consumption of certain probiotic
strains have been shown to enhance nonspecific immunity, including phagocytosis
and lymphocyte proliferation (3) demonstrating the effectiveness of probiotics
in stimulating cellular immune responses. Healthy middle-aged and elderly men
and women have been shown to experience a significant enhancement of cell
phagocytosis and natural killer cell tumor killing activity following twice
daily consumption of B. lactis. The authors suggest that the enhanced immunity
observed in relation to the B. lactis may be largely related to the secretion
of pro-cellular immunity cytokines such as interleukin-12 and interleukin-18,
which simulate natural killer cell activity and interferon production. These
results support that of another study in which consumption of B. lactis was
positively associated with increases in the total proportions of T lymphocytes
and natural killer cells. (4)
Probiotics play an essential role in the intestinal mucosa barrier,
including modulating intestinal immune response and competitively inhibiting
the adhesion of pathogenic bacteria to the epithelial wall of the intestine.
Intestinal epithelium plays an important role in innate immunity. When
stimulated by cytokines, such as TNF-[alpha], the intestinal epithelia release
pro-inflammatory cytokines, including IL-8 and IL-10. However, in some
gastrointestinal diseases, such as inflammatory bowel diseases (IBD) and acute
gastroenteritis, cytokines are activated and produce excessive inflammatory
products negatively affecting the immunological capacity of the epithelial
cells. Resident Bifidobacterium and Lactobacillus actively inhibit the
pro-inflammatory response by inhibiting the secretion of IL-8, thereby
suggesting the use of probiotics in the management of intestinal diseases. (5)
This has vast applications for 'quenching' a potentially out-of-control immune
system seen in autoimmune diseases and disorders of inflammation.
Many probiotic strains have been studied in relation to their role in
the control of inflammatory responses to intestinal antigens. (6-8)
Specifically, many clinical and experimental studies indicate that imbalances
in the microflora of the gut are associated with intestinal inflammation. For
example, one group studied the effect of oral administration of Lactobacillus
rhamnosus on cytokine secretion and T lymphocyte activation, thus demonstrating
the positive immunomodulating effects of oral administration of lactic acid
bacteria. (8) Healthy participants taking a daily oral dose of 2 billion colony
forming units (cfu) of L. rhamnosus experienced a reduced secretion of
pro-inflammatory TNF-[alpha] and increased IL-10 and IL-4 activity.
TNF-[alpha] is key to the pathogenesis of altered mucosal immunity. A
critical factor in the pathogenesis of Crohn's disease is the secretion of
TNF-[alpha] by T lymphocytes. (6) Co-cultures of inflamed tissue with various
probiotic strains have been proven to significantly reduce TNF-[alpha]
secretion. (5,6) Since transcriptional control of IL-8 is mediated by
transcription factor NF-[kappa][beta], it is hypothesized the normal intestinal
microflora down-regulates inflammation by inhibiting NF-[kappa][beta]
activation. This hints at a possible genomeceutical intervention point for
probiotics.
Therapeutic administration of probiotics is often advocated for their
immunomodulatory properties and anti-inflammatory activities at mucosal barrier
sites. (3,4,8) However, only recently have the molecular mechanisms by which
probiotics modulate immune responses been elucidated. Immuno-stimulating DNA
sequences have been shown to effectively reduce or prevent symptoms of colitis
in animal studies. (9) Furthermore, administration of irradiated probiotics
significantly improve experimental colitis in murine models, as do viable
probiotic strains, suggesting the anti-inflammatory activities associated with
probiotics are mediated by their own DNA, rather than products of their
metabolism or intestinal colonization. (9) This theory is further supported by
data suggesting genomic DNA released by exogenous bifidobacteria provide a
stimulus for mucosal IL-10 production in human peripheral blood mononuclear
cells. (7) The interesting conclusion that may be made in light of this
research is that dead bacteria ingested during probiotic administration provide
a therapeutic-effect in addition to the viable cells.
Specific Immunity
Ingestion of specific probiotics has been
shown to have immunomodulatory effects on many aspects of humoral and
cell-mediated immunity. In one study designed to examine the relationship
between oral administration of probiotics and immunity in mice, the results
indicate strain-dependent variation in the ability of probiotics to influence T
cell activation. L. rhamnosus and L. acidophilus were found to effectively
stimulate Th1 cells, whereas B. lactis showed no effect. (10) Th1 cells are
known to suppress immunoglobulin E (IgE), an indicator of allergy. In this
study, Th1 cells inhibited IL-4 secretion, thereby suppressing IgE production.
It can then be postulated that certain strains of probiotics may inhibit
IgE-mediated allergic responses through selective stimulation of Th1 cells.
(10) In fact, probiotics have successfully been used in the prevention and
treatment of allergic disorders.
Probiotics, Pg2
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