When Prof. Gregor Reid was invited to give a lecture in Israel, he jumped at the chance. A research study at the Weizmann Institute of Science attacking probiotic products angered him and motivated him to correct the error. The truth is, however, that his anger is not confined to that study. As a probiotic researcher, his enthusiasm about the potential of the products that he and his colleagues are developing almost equals the disgust that he feels about probiotic products that he says are not based on real research.
"The probiotics market has a $60 billion annual turnover, but it rests on the effectiveness of a few products. The rest of the products are fed by people giving up on medicine," he says. "For example, for 40 years, nothing changed in treatment of vaginal infections, until we came along. Had it been a disease affecting men, they wouldn't have waited so long."
This is not the only problem. Even if a medical source recommended that you take a probiotic product, it is usually not accompanied by an instruction of which bacteria you should take, and in what dosage. The attitude is, "Try it and see. If it doesn't work, at least it won't hurt." For Reid and many other researchers, however, microbiome research, the composition of bacteria in our bodies, will be one of the most influential medical fields in the future. The recognition that most of the DNA in our bodies is actually bacterial DNA, and that any drug we take and food we eat is affected by the composition of our bacteria, can bring us to the edge of an entire new area of medicine.
Probiotics, which seeks to add useful bacteria to the body's bacterial composition, is only the tip of the microbiome research iceberg. Studies have already discovered that probiotic treatment is effective in certain kinds of abdominal pain and urinary tract infections, but many doctors are in no hurry to prescribe these products, because they have not been through the conventional track that drugs go through. The food supplement companies, on the other hand, sell innumerable probiotic products for various problems, some of which have no research at all proving their effectiveness.
Reid is a professor of microbiology and immunology at Western University in Canada and the Endowed Chair in Human Microbiome and Probiotics at the Lawson Health Research Institute. He is visiting Israel as a guest of Altman Health, which manufactures and markets probiotic products and conducts research in the field. "I thought that it was an opportunity to correct the mistakes and deliver a message about useful microbiomes," he told "Globes."
Doctors laughed, but women tried the products
Reid began researching probiotics in 1982, before the term had even been invented. It was already known that there were "good bacteria" needed by the body, but which bacteria were needed and beneficial was unknown, and it was not yet possible to add them to products.
One of Reid's groundbreaking studies involved the identification of bacteria present in the vaginas of women who were healthy, but lacking in women who had a tendency to develop urinary tract infections. He discovered that the most common family of bacteria in the vagina was lactobacillus, whose function was to convert sugar to lactic acid, which is found in milk. These bacteria are also common in other places in the body, and especially in men and women's intestines.
Obviously, when we proposed to the scientific community that women put yoghurt into their vaginas, they laughed at us," Reid remembers, "but women whom we treated agreed to try it, because they were desperate, and because the treatment had no side effects."
It appears that lactobacillus competes in the urinary tract with E. coli bacteria, which originate in feces and usually cause infection. It is practically impossible to prevent contact between E. coli bacteria and the urinary tract, even through hygiene measures.
A recent study compared taking a probiotic product based on strains of lactobacillus with taking antibiotics among women with a tendency to develop urinary tract infections. It was found that antibiotics prevents about four out of seven infections in the same year, while probiotics prevented an average of 3.5 infections. This sounds like antibiotics are preferable, but when the fact is taken into account that probiotics have no side effects and no resistance to them is developed, at least none that is currently known, the advantage is no longer so clear.
Because of the widespread prevalence of lactobacillus in our bodies, "It is the only bacteria worth researching," jokes Reid, who developed a product now sold to millions of people around the world by Danish company Chr. Hansen. On a serious note, he says that probiotics is an entire world.
Since the first attempts to treat urinary track infections with lactobacillus, Reid and his team have had quite a few successes. For example, his research shows that there were 40 different toxins in pregnant women, and lactobacillus probably connect to and eliminates some of them.
Another study that focused on breast infections among nursing women found that there were lactobacillus bacteria in the mammary glands of different strains than those present in the vagina. "It turns out that mother's milk contains bacteria that the mother should transmit to the child," Reid explains. "When we gave nursing mothers probiotics with strains isolated from mother's milk, we succeeded in reducing the rate of infection in the nipple and breast."
A follow-up study by Reid showed that women who contracted cancer (whether or not they had nursed) had a different bacterial composition than women without cancer. The women with the disease also had fewer bacteria from these strains of lactobacillus. This study is still ongoing, but it is already generating great interest.
The effectiveness of probiotic treatment is not confined to human beings. Epidemics affecting bees, for example, are threatening to destroy many kinds of plants in the world and make them extinct, because the plants need bees to fertilize them. The bees are apparently dying because of a pollutant, and probiotics can provide some protection against these pollutants. Farmers are now including a probiotic products developed under Reid's sponsorship in the food that they leave for bees in their hives in order to support their proliferation and induce them to remain in the area.
"They throw in a few bacteria and say it's good"
Reid, who was a member of the UN team that defined what a probiotic is, estimates that only 10% of the 300 probiotic products launched each year really fit the definition. As far as he is concerned, every company that wants to define its product as "probiotic" should meet four criteria: a precisely defined strain of bacteria, including its genome; a clinical trial with a control group showing the advantage of using the bacteria over a placebo; an effective dosage of the bacteria as shown in trials (many probiotic products currently contain bacteria whose effectiveness has indeed been scientifically proven, but in substantially lower dosages than those tested in research); and applying the idea that there is no such thing as a "healthy probiotic;" there is only the right treatment for a person in a specific medical condition. Reid thereby contradicts the opinion of other researchers, and certainly that of marketers, who declare that they know how to devise a "healthy bacterial composition" for every person.
"Investing in companies resting on sand"
The aspiration to create a healthy bacterial composition was to a great extent inspired by treatments like fecal microbiota transplants - an unpleasant name for an unpleasant, but effective, procedure: all of the patient's feces are washed away, momentarily making the intestine almost sterile, and then capsules containing feces from a healthy person are inserted. Patients are cured in this way without knowing exactly the difference between the feces. This treatment has saved thousands of lives to date.
A person recently died from this treatment in the US, but Reid says that the fatality resulted from bacteria in ostensibly healthy feces. In most situations, the bacteria's presence would have been detected in advance, preventing the administering of the fecal capsule.
Fecal microbiota transplants are so exciting that several people have begun carrying them out independently. Reid does not recommend this, of course, but admits that the procedure corresponds to the dream of trading bodies with a healthier person. The possibility of fecal microbiota transplants is now being researched with many diseases, from cancer to metabolic diseases.
Reid nevertheless contends that it is still very difficult to research bacterial composition and assign each person a cocktail that will give each person what he or she is missing and get rid of what is harmful, which is the vision of the sector. The task, which involves big data, is very difficult to put into practice, and even more difficult to conduct clinical trials to prove the effectiveness of a given cocktail, in comparison with another cocktail. "Assume that we have grown this bacterial cocktail. Can we be sure that the bacteria in it won't affect each other, or than one of them won't become dominant at the expense of the others?", he asks.
At least for the near future, he says, the main products developed will contain one type of bacteria, or at most two or three similar types.
Reid is also suspicious of companies that offer diagnosis on the basis of intestinal bacteria. He compares them to companies offering a genetic profile "for the fun of it." These companies explain to consumers, for example, that they have "fattening" bacteria, or lack bacteria related to gluten dissolution.
One of these companies, uBiome, has already had its misdeeds exposed. The FBI recently raided the company's offices because of problems with its books. Anonymous sources told the media that the company's science was no better than its bookkeeping.
One example that Reid gives of practice with no grounding in research is giving bacteria from a mother's vagina to a baby delivered by Caesarian birth who "missed out" on the opportunity to pass through the birth canal. Studies have shown that vaginally born babies are slightly healthier on the average, "but what if the mother has herpes in the vaginal canal?", Reid asks. "Do we know with certainty that we're improving the baby's situation? This isn't the way things are done in medicine. If you find the specific bacteria lacking in children delivered by Caesarian, isolate it, prove its effectiveness, and then give only that bacteria as probiotic treatment, you might have a product. Otherwise, it's just a pretty story. People invest in these companies, which I think rest on sand."
As for Israeli company DayTwo, which offers its customers a menu based on the way their specific bacteria break down sugar from various food, Reid says that while he is not thoroughly familiar with the company, he does not believe that definite conclusions can be drawn about the microbiome composition of the entire intestine. "I don’t think that this is the right way to develop a microbiome-based product. The general idea is good, but the big question is whether good enough data can be gathered now," he explains. The company did not respond to his comments.
In the next stage, Reid wants to examine the effect of bacterial composition on drugs. "When drugs enter the intestine, they first of all meet bacteria that change the drug. It is important to understand how each body responds to this. For example, if we gave someone a drug that inhibits testosterone production in order to treat prostate cancer, we have to keep in mind that there are also bacteria that produce testosterone. The question is how it can be treated without disturbing the intestinal balance. There is a long way to go."
Published by Globes, Israel business news - en.globes.co.il - on July 21, 2019
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