a mode of probiotic action is to stimulate the immune system

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usual tortured rats.

" Probiotics, the

trendy =93good bacteria=94 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 gastrointestinal problems. Although the

effectiveness of these bacteria has been attributed to their live,

metabolic activity, viable probiotics can=92t 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. =93Our goal was to

address whether the metabolic activity of probiotics was mandatory for

their protective effect,=94 said the study=92s 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,

=93live=94

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=92s 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=92s first author,

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. ### Sue Pondrom (619) 543-6163

spondrom@...