Probiotics Beneficial Even When
Inactive, According To UCSD Study
By Sue Pondrom
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.
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
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.
“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
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
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.
Media Contact: Sue
Pondrom (619) 543-6163