Bacterial DNA reduces inflammation in mice

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.

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.

Reference: D Rachmilewitz et al. Toll-like receptor 9 signaling mediates the anti-inflammatory effects of probiotics in murine experimental colitis. Gastroenterology. (Feb. 2004) DOI:10.1053/j.gastro.2003.11.019.

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