Research
Beneficial Bacteria
Part 3
Bacterial DNA Reduces Inflammation In Mice
2-3-2004
DNA from inactivated "probiotic" bacteria triggers
a specific anti-inflammation immune response in mice with
experimental colitis, researchers supported by the NIH’s
National Institute of Allergy and Infectious Diseases (NIAID)
have discovered. Led by Eyal Raz, M.D., of the University
of California, San Diego (UCSD), the investigators provide
a possible explanation for the observed benefits of consuming
probiotics, supplements from bacteria and other microbes,
regarded by some as helpful in maintaining or restoring
intestinal health. Knowing how probiotics work could give
scientists a way to identify and select which probiotic
bacteria might be effective against such human ailments
as inflammatory bowel disease (IBD).
Probiotics
have shown promise for treating such IBDs as Crohn's disease
and ulcerative colitis, both of which cause periodic intestinal
inflammation. But scientists have had many theories of how
these mixtures of "good" bacteria work, notes
Marshall Plaut, M.D., of NIAID’s Division of Allergy,
Immunology and Transplantation. Plausible theories suggested
that proliferation of the living bacteria either generated
helpful metabolic products or crowded out "bad"
intestinal bugs. Prior to this study, the general thinking
about probiotics, which include bacteria like those found
in yogurt, has been that they mediate their effects through
some kind of non-specific action, adds Dr. Plaut.
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Dr. Raz and his colleagues, whose work is published
in the February 2004 issue of the journal Gastroenterology, irradiated
a commercially available probiotic preparation, halting bacterial
proliferation, but preserving its DNA. When given to mice, the irradiated
probiotics performed as well as live bacteria in reducing inflammation.
They also found that purified probiotic bacterial DNA alone similarly
reduces inflammation in mice with experimentally induced colitis.
The researchers also showed that probiotic DNA acts
in a specific way by activating a defined element within the innate
immune system. In animals, including humans, components of the innate
immune system play complementary roles in initiating, then halting,
inflammation. Improperly regulated inflammation is one symptom of
IBDs.
An innate immune system protein called TLR9 is a pivotal
player in the chemical signaling chain that slows inflammation. In
a series of experiments, the UCSD team showed that probiotic DNA exerts
its effects through TLR9. Indeed, mice without the gene for TLR9 protein
cannot benefit from probiotics, either living or irradiated, or from
probiotic DNA.
Taken together, insights into mechanisms of probiotic
activity open new possibilities for probiotic therapies. For example,
say some researchers, purified probiotic DNA or irradiated probiotics
may be safer than viable preparations, and could be used by people
with compromised immune systems.
Dr. Raz also received support for this research from
the National Institute of Diabetes and Digestive and Kidney Diseases,
a part of the NIH.
NIAID is a component of the National Institutes of
Health (NIH), which is an agency of the Department of Health and Human
Services. NIAID supports basic and applied research to prevent, diagnose
and treat infectious and immune-mediated illnesses, including HIV/AIDS
and other sexually transmitted diseases, illness from potential agents
of bioterrorism, tuberculosis, malaria, autoimmune disorders, asthma
and allergies.
Press releases, fact sheets and other NIAID-related
materials are available on the NIAID Web site at www.niaid.nih.gov.
This
article has been adapted from a news release issued by NIAID, www.niaid.nih.gov.
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