07/27/2014 10:15 EDT | Updated 09/26/2014 05:59 EDT

How Probiotics Could Prevent Obesity and Other Chronic Diseases

The value of good germs has been known for decades. The incorporation of a variety of bacteria such as Lactobacillus into our diet has been shown in research, clinical trials and anecdotally to be beneficial. Today, the use of probiotics in certain areas of medicine, such as the prevention of antibiotic-associated complications, is recommended.

While the good news continues to grow, there may be an even brighter future ahead thanks to a technique known as genetic engineering, or GenEng. This was epitomized last month when an international group of researchers illustrated how the use of genetically modified probiotics could prevent chronic disease. Using only a specifically designed bacterium, they could prevent obesity in mice giving them a healthier life.

Lab-based manipulation of bacterial DNA -- the basis of GenEng -- is not a new concept. Since the discovery of DNA, research has been focused on ways not only to understand the nature of the genetic code, but also how to manipulate it for benefit. By the 1970s, scientists were finding ways to remove, insert, and alter genes in bacteria revealing novel directions for research.

At first, GenEng was for fundamental science but eventually, medicine came calling. There was a need for mass production of valuable yet scarce medicines, such as insulin, and this technique seemed to be the answer. As certain bacteria, such as Escherichia coli, could multiply in as little as 20 minutes, these once despised organisms were thought to be the future pharmaceutical factories saving both time and money.

The first medical achievement happened in in the early 1980s when E. coli was modified to mass produce insulin. Because of this, the trend grew exponentially such that nearly 30 per cent of all pharmaceuticals were being produced by these bacterial benefactors. They included hormones, immune therapies, and vaccines, some of which are still being prescribed today.

All the while, the concept of a genetically modified microorganism (GMM) was being imagined. The idea of feeding humans bacteria normally found in the gut with slight modifications appeared to be a significant step forward. Yet, there was a significant hurdle; the strains used in GenEng were lab-based and did not enter the human food chain. In order for this direction to move forward, an E. coli probiotic was needed.

Fortunately, one had been found nearly a century earlier. In 1917, the German doctor and microbiologist, Alfred Nissle, discovered a form of E. coli with probiotic potential. The strain was later named after him, E coli Nissle 1917, and became the focus of many lab-based and clinical-based studies. In the lab, notable benefits of the bacterium included prevention of pathogen colonization,interference with infection, and improvement of immune function in cases of chronic colitis.

There was more to come in clinical trials. In 2007, Nissle 1917 was used to help stop the onset of diarrhea in infants and toddlers. The results suggested the bacterium could not only stop pathogens in their tracks but also balance the immune response to prevent further inadvertent harm. Over the next two years, the bacterium was put to the test against ulcerative colitis and irritable bowel syndrome. In both cases, improvement was seen suggesting this probiotic could be used to complement other medicinal treatments.

But while complementary therapy was possible, some researchers wondered if the bacteria themselves could act both as probiotic and therapy at the same time. By using genetic engineering, Nissle 1917 could be given all the molecular tools necessary to provide a benefit to the host saving both time and money. Last year, such a concept was reported and found to be feasible, at least in the lab. But the question was whether this would work in animals.

This is where last month's research took over. The team wanted to explore the potential of preventing obesity using GMM. Using GenEng, the group modified Nissle 1917 such that it would produce a natural body chemical known as N -acyl-phosphatidylethanolamine (NAPE). This molecule is known to suppress appetite and reduce food intake in mice fed a high-fat diet and can help to prevent obesity as well as insulin resistance, and liver steatosis.

The researchers fed mice the GMM -- as well as a placebo and a normal version of Nissle 1917 -- for eight weeks in addition to the high fat diet. As expected, the mice in the control and normal Nissle groups gained weight while the mice fed GMMs lost weight thanks in part to a reduction in appetite.

In addition, the GMM-fed mice had no energy deficits, kept diabetes at bay and also had healthier livers. But the most surprising observation was the long-term persistence of the bacteria, which stuck around for up to six weeks after treatment. During that time, the mice stayed thin and stayed healthy.

Though this study is limited to mice, the results suggest there may be an avenue to explore the use of GMMs. They could provide not only their usual benefit but also factors to prevent or stem certain chronic conditions in humans including obesity, diabetes, liver disease and a host of others. Although this may mean an acceptance of what might be called a genetically modified organism, we may one day have a means to naturally help ourselves by trusting bacteria to keep us healthy when our genetics and lifestyle choices may not.


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