I wrote a blog last year about probiotics and have had many questions about their use as a result. Most of us have heard about the benefits of live bacteria as probiotics. Probiotics are the trendy “good bacteria” found to aid disorders such as Inflammatory Bowel Disease (IBD), allergies, and even some forms of cancer, surprisingly have been shown to contain immune system-stimulating DNA that makes them just as effective when inactivated, as when consumed as live microorganisms in dairy products such as yogurt.
I first became aware of these data hearing a talk by Professor Eyal Raz at the University of California, San Diego (UCSD) School of Medicine whom, I believe, first reported the potential to use inactivated probiotics in food products ( February 2004 issue of the journal, Gastroenterology). In addition, the study provided a mechanism to determine and to select which probiotic bacteria are best for patients with IBD.
A probiotic is a bacterium that contributes to the health and balance of the intestinal tract, working to balance the microbiome. Although recent scientific studies have proven the therapeutic benefit of these good bacteria, the use of probiotics dates back thousands of years. People in ancient Babylon, for example, drank sour milk to alleviate gastrointestinal problems.
Although the effectiveness of these bacteria has been attributed to their live, metabolic activity, viable probiotics often are not suitable for addition to food because the bacteria induce fermentation, leading to changes in the taste, texture, and freshness of the product. Thus, the bacteria have only been used in a very narrow range of products such as yogurt.
Professor Raz's study addressed whether the metabolic activity of probiotics was mandatory for their positive effects. Importantly, previous studies had tried heat killing of probiotics to inactivate them, but this process destroyed the cellular structure, conformational states of the molecules, and ruined the beneficial aspects. In the new experiments, the team used gamma radiation on the bacteria, reducing metabolic activity to a minimum, but maintaining molecular structure.
Next, the UCSD researchers 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 that 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. The studies also demonstrated that the positive effects of the probiotics could be effected through oral or subcutaneous adminstration of the probiotics.
These studies are a breakthrough in understanding how probiotics work, and also in the commercialization of probiotics for the mass market.