Research
Beneficial Bacteria
Part 2
Probiotics Beneficial Even When
Inactive, According To UCSD Study
2-2-2004
Probiotics, the trendy "good bacteria" found to
aid disorders such as Inflammatory Bowel Disease (IBD),
allergies and even some forms of cancer, contain immune
system-stimulating DNA which makes them just as effective
when inactivated, as when consumed as live microorganisms
in dairy products such as yogurt.
 Eyal
Raz, M.D.
Reported
in the February 2004 issue of the journal Gastroenterology
by researchers at the University of California, San Diego
(UCSD) School of Medicine and the Shaare Zedek Medical Center
in Jerusalem, Israel, the findings offer the potential to
use inactivated probiotics in food products. In addition,
the study provides a mechanism to determine and to select
which probiotic bacteria are best for patients with IBD.
A
probiotic is a bacterial organism that contributes to the
health and balance of the intestinal tract. Although recent
medical studies have proven the therapeutic benefit of these
good bacteria, their use dates back thousands of years.
People in ancient Babylon, for example, used sour milk to
alleviate gastrointestinal problems.
Although
the effectiveness of these bacteria has been attributed
to their live, metabolic activity, viable probiotics can’t
be added to food because they induce fermentation, changing
the taste, texture and freshness on an hourly basis. For
that reason, the bacteria have only been used in a very
narrow range of products such as yogurt.
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"Our
goal was to address whether the metabolic activity of probiotics was
mandatory for their protective effect," said the study’s
senior author, Eyal Raz, M.D., professor of medicine at UCSD. Raz
noted that previous studies had tried heat killing of probiotics to
inactivate them, but this process destroyed the cellular structure
and beneficial aspects. In the new experiments, the team used gamma
radiation on the bacteria, reducing metabolic activity to a minimum.
Next,
the team administered the irradiated probiotics to mice with experimentally
induced colitis, which is similar to human IBD. The irradiated probiotics
effectively ameliorated the colitis, as did the administration of
viable, "live" bacteria to another group of mice with colitis.
This indicated that inactivated probiotics were as effective as live
probiotics.
The team reasoned that the beneficial, anti-inflammatory
activities seen with the inactivated probiotics could be the product
of the innate immune system, the body’s instant response to
invasion by pathogens. Specifically, the researchers looked at molecules
called toll-like receptors (TLR) that are known to respond to a variety
of signature microbial molecules. In order to determine which TLR
responded to probiotics, the team administered a chemical called chloroquine
to mice deficient with several different TLRs. Chloroquine had recently
been demonstrated to inhibit TLR9 activation, and it was only in the
TLR9-deficient mice that the probiotics were ineffective in alleviating
colitis.
In addition to studying the normal and irradiated
probiotics on mice, the researchers tested a synthetic form of bacterial
DNA called immunostimulatory (ISS) oligonucleotide (ODN), a short
segment of synthetic DNA with immunostimulatory properties, which
mimics bacterial DNA. In a previously published paper in Gastroenterology*,
ISS-ODN had been found to reduce the harmful effects of experimental
colitis in mice, indicating that it worked in a manner similar to
probiotics.
According
to the study's first author, Daniel Rachmilewitz, M.D., Division of
Medicine, Shaare Zedek Medical Center, evaluation of the immunostimulatory
activities of probiotics may also provide an easy screening system
for the selection of probiotic bacteria prior to their clinical use.
In another portion of the study, the team also demonstrated
that probiotics and ISS-ODN could be administered either orally or
subcutaneously.
Additional authors on the study were Fanny Karmeli,
M.Sc., Constantin Reinus, M.D., and Bernard Rudensky, M.D., Shaare
Zedek Medical Center, Jerusalem, Israel; Kyoko Katakura, M.D., Tomoko
Hayashi, M.D., Ph.D., Jongdae Lee, Ph.D., and Kenji Takabayash, Ph.D.,
UCSD Department of Medicine; and Shizuo Akira, M.D., Ph.D., Kiyoshi
Takeda, Ph.D., Department of Host Defense, Research Institute for
Microbial Diseases, Osaka University, Japan.
The study was funded by the National Institutes of
Health and the Broad Medical Research Program of the Eli and Edythe
L. Broad Foundation.
This
article has been adapted from a news release issued by University
of California at San Diego, www.ucsdnews.ucsd.edu
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