The Science Behind Probiotics and Prebiotics

You’ve got to hand it to Dannon. At a time when E. coli scares put product safety under the microscope, the yogurt giant has convinced notoriously squeamish Americans to spend as much as twice the going rate on yogurt that’s literally infested with bugs.

How did they do it? Not by exploiting some latent affection for microbes, but by shining the steely eye of science on both the safety and the outright advantages of the bacteria in question.

That bacteria would be Bifidus animalis DN-173010—trade name Bifidus Regularis—and the product it inhabits is Activia, Dannon’s blockbuster and a bellwether of probiotic formulation to come. Activia is a bona fide phenomenon, posting nearly $2 billion in worldwide sales in 2006, ranking it among the most-successful product launches in U.S. food-biz history, according to BusinessWeek.

Dannon deliberately pitched its probiotics as capable of surviving the stomach into the large intestine, where they modify intestinal transit to alleviate uncomfortable bloating and aches. As a result, gut health is a topic for polite conversation. And that’s no mean feat. As Terri Rexroat, global product manager, lactic cultures, Cargill Texturizing Solutions, Minneapolis, points out, “Increasing consumer awareness and education was the first real step toward removing the U.S. societal stigma associated with talking about intestinal and digestive health.”

Gut feelings

Probiotics are not your average bacteria. In 2002, an expert panel of the Food and Agriculture Organization of the United Nations (FAO) defined probiotics as “live microorganisms administered in adequate amounts which confer a beneficial health effect on the host.” By definition, these bugs are good for us. And their benefits begin in the gut.

The lumenal surface of the large intestine is the front line in our immune defense, the prime interface between outside and in. Its ability to carry out its duties owes greatly to its microfloral makeup. The colon contains thousands of bacterial species numbering as high as 1011 to 1012 cells per gram of contents. Many of these bugs shore up the barrier function of our intestinal lining, guarding against infections and allergies in the process. Some help metabolize indigestible dietary components—fiber and, in the case of the lactose-intolerant, lactose. Some produce vitamins that we can’t produce on our own. And others metabolically “defuse” dietary carcinogens, mutagens and toxins.

Stressing the strain

For an intestinal troop to rank as a full-fledged probiotic, it’s got to be the right caliber. While all probiotics are friendly organisms, “not all friendly organisms are considered to be probiotics,” Rexroat says.

That’s why, in addition to the FAO definition, the joint FAO/World Health Organization (WHO) “Guidelines for the Evaluation of Probiotics in Food” set out further criteria, starting with the requirement that probiotic bacteria display documented benefits not merely at the genus or species levels, but at the level of the strain. Beyond that, the probiotic must reside in an internationally recognized culture bank to allow for replication of current and future research; must have undergone sufficient and appropriate in vitro and animal trials to support its benefits; must maintain viability at required levels during a product’s normal shelf life to achieve benefits in the host; must be subject to further studies in the host; and—above all—must be safe.

By these lights, most probiotic strains fall into the genera Lactobacillus and Bifidobacterium, plus some Streptococcus thermophilus, Escherichia, Enterococcus and Bacillus strains, and one strain of Saccharomyces cerevisiae yeast, called S. boulardii. Their presence promotes a healthy gut environment through their production of lactic and acetic acids, which drive off pathogens by lowering gut pH. More remarkable are the hundreds of published clinical and observational studies detailing their effects not only on the body’s normal functions, but on specific diseases.

The website USProbiotics.org gives a comprehensive rundown of these benefits, and the state of the science it lists hints at possible roles in everything from allergy prevention to alleviating symptoms of irritable bowel syndrome and inflammatory bowel diseases to preventing kidney-stone formation. Studies have investigated probiotics’ ability to decrease risk for certain cancers, lower blood pressure and cholesterol, reduce incidence of dental caries, and even battle Helicobacter pylori.

No matter the benefit, experts stress the importance of strain. As Peggy Steele, global business director, probiotics, Danisco Cultures, Madison, WI, says: “All probiotic health benefits are demonstrated via scientific studies using a specific strain or blend of strains for which structure/function claims can be made. Benefits documented with one strain cannot necessarily be transferred to other strains of the same species, as results are believed to be strain-specific.”

So, outside their general ability to confer health benefits, probiotics transcend generalization. You can no more attribute the effects of one strain to another than you can credit the benefits of vitamin D to vitamin C. And, just as vitamin D may be great for bone strength but do little for carbohydrate metabolism, a probiotic strain that can shorten the duration of diarrheal illness may have no effect on the common cold.

The sound of science

In making sense of these causes and effects, the sound science behind probiotic benefits proves its worth. While FDA has yet to bless a health claim for probiotics, structure/function claims are common. These don’t receive the same scrutiny as formal health claims, but still merit substantiating evidence.

“What we’re seeing in the market is that there’s becoming almost an assumed health benefit of probiotics,” says Mike Bush, vice president, business development, Ganeden Biotech, Mayfield Heights, OH. “But, in order to make a claim on a product, you have to do good clinical trials with the finished product. We always encourage our customers to do as much science as they can possibly do. Once you’ve got the clinical work, then you can say things like ‘proven to boost the immune system,’ or whatever the trial indicated.”

Mary Ellen Sanders, a consultant in probiotic microbiology with Dairy & Food Culture Technologies, Centennial, CO, and executive director of the International Scientific Association for Probiotics and Prebiotics (ISAPP), Davis, CA, is encouraged by the rigorous inquiry of probiotic research. “Many of these companies have piggybacked on research that’s been done painstakingly in different research labs over the course of years,” she says. “So, it’s not as if these claims were just picked out of the air.” Yet, when asked which claims deserve the most confidence, she says, “it becomes a little difficult to be very quantitative about that.”

Frankly, we’ve still got a lot to learn. Even the bedrock assumption that probiotics regulate intestinal flora isn’t as solid as it seems. “Not that it’s not important,” Sanders says. “It is important. But the situation we’re in today, if you want to have a really strong science-based perspective, we’re just now starting to characterize fully what populations of microbes are even there, and how they communicate with the host, how the host communicates with them, what roles they play in terms of driving our health, and to what extent consuming probiotics really influence that. Less is known about that than you might think.”

Stressing that she’s not a clinician, Sanders feels safe saying that, when looking at the science as a whole, “there are probably more publications and more evidence for antibiotic-associated diarrhea and infectious diarrhea in children than any other specific topic.” Gut and immune health also receive close attention, with supporting studies that “are really focused on very specific endpoints,” she adds.

Steele notes that probiotics are showing up in “‘cosmetofoods’ in skincare formulations,” and that manufacturers are targeting benefits to specific audiences—children, women, seniors—with specific needs. Her company recently presented a study on children younger than five that documents the effects of its probiotics on reduced incidence and duration of cold and flu symptoms. The formulation, she says, “reduced the number of sick days by almost half, and the number of antibiotic prescriptions by 80%.”

These boots-on-the-ground results excite Sanders. While it’s all well and good to link probiotic consumption to, say, enhanced expression of certain immune biomarkers, “having said that, what does that mean?” she asks. “At the end of the day, does that make me healthier? Those animal studies and biomarker studies in humans are very important for understanding mechanisms of effect, but to me, the more-convincing studies are the ones that note fewer absences from work, reductions in how many colds you get, other respiratory illnesses, diarrheal illnesses”—real-world improvements.

Thus, Sanders’ message is: “Let’s look at the endpoint health effects.” The best advice she can give, “at least for what we understand right now, comes from recommending products that have studies that have shown a real effect. That way, you know what dose to use, what subjects were studied, what degree of effect was seen and what might be expected in the consumer.”

Such standards apply especially to dosage. “Just as the strain that is used to claim a specific benefit is important, so is the dosage or the amount of living probiotic cells that is ingested or applied,” Steele says. “It is key that the amount of probiotic cells at the end of a food product’s shelf life should be identical to the dosage used in the scientific studies.”