Early this year, Nestle Health Science announced a $65 million investment in a nutritional push to improve the health of gut bacteria. And they are not the only ones looking for gold in bugs. The burgeoning field of the microbiome—the bacteria, fungi, viruses and archaea that live in and on us—is earning sizable consumer interest and industry attention. Probiotic foods comprised a nearly $7 billion industry in 2013—and are projected to jump to nearly $10 billion by 2018. And the probiotic supplement market, which brought in approximately $1.2 billion in 2013, is expected to almost double in size by 2018.

And for good reason. The gut microbiome, we are learning, is linked to numerous aspects of health—from inflammation and auto-immune diseases to weight gain and mood. As part of this gamut of health connections, researchers also have their eye on its role in digestive disorders, including the fast-growing concern of gluten sensitivity. This market’s size and projected growth alone are enticing: gluten-free products are projected to bring in some $14.4 billion by 2016—almost double the revenue from 2012.

Gut microbes and gluten sensitivity are a natural match—both scientifically and commercially. “There’s been a huge explosion in funding a lot of microbiome research, and of course gluten sensitivity is a huge area to study,” says Florence Comite, a personalized precision medicine physician in New York City, who sees many patients who are trying to avoid gluten.

But with the rapidly evolving science and consumer awareness into both the health impacts of the microbiome and the nature of gluten sensitivity, the landscape is likely to be a dynamic one, shifting toward more dialed-in products and greater customer interest in healthful, effective products. “We will move into the new world as people make probiotics for very specific reasons,” says Joseph Murray, a gastroenterologist who specializes in gluten sensitivity and intestinal inflammation at Mayo Clinic in Minneapolis. And that includes diving into the still-perplexing world of gluten sensitivity.

Evolving science

We are only beginning to learn the extent of the microbiome’s ability to alter health. In 2013, researchers announced in the New England Journal of Medicine that they were able to conquer severe Clostridium difficile infections in 90 percent of patients through a wholesale transplant of a healthy person’s microbes. These strikingly positive results spurred increased confidence in the potential and power of the gut microbiome to impact a range of health issues.

Food sensitivities are a logical avenue for microbiome research—and by extension, probiotic products. “There’s a perception that gut microflora can alter sensitivities to food and gastrointestinal symptoms,” says Daniel Leffler, a gastroenterologist and director of clinical research at the Celiac Center at Beth Israel Deaconess Medical Center in Boston. “And many patients are [already] on probiotics as one way of potentially trying to alter the microbiome,” he says. “It’s clear that there is an interaction between intestinal sensitivity and the gut microbiome, [but] it’s something we’re just beginning to understand.”

Gluten sensitivity itself—which can generate a variety of symptoms, including abdominal pain, bloating, upset stomach and headaches—has been the subject of some debate. For those who are severely allergic to gluten, a blood test can definitively diagnose celiac disease. “Beyond that, you get into a grey zone,” says Murray, who also authored the book Mayo Clinic Going Gluten Free. For the rest of these consumers, there is yet to be a reliable test for non-celiac gluten sensitivity. Even among those with non-celiac gluten sensitivity, not all individuals are alike, adds Comite. “I think of it on a spectrum,” she says.

For many, gluten might not even be the problem. From his research, Murray finds that many people who complain of gluten sensitivity are in fact allergic to another component of wheat. Though gluten is found in several grains, including barley and rye, many “gluten” studies to date have focused on wheat-based foods, rather than gluten specifically. In short, Leffler says, “there’s a lot of confusion, because it’s a confusing science.”

Adding in the microbial element is creating even more complexity. Patients with celiac disease show different gut microbe patterns from healthy individuals. But little research has been done for non-celiac gluten sensitivity, in part because the population is so difficult to define, Leffler notes. And Murray points out that many people who identify as gluten-sensitive have already changed their diets, making sound gut studies even more difficult to run. ➪

The reason for that methodological hiccup comes down to microbes: “The main determinant of our flora is what they eat,” Murray says. Food and supplements can have a rapid impact on gut microbe populations. “Your bacteria can change by tomorrow if you eat something different,” he says. A 2013 study in Nature found that shifting healthy volunteers’ diets could drastically alter their microbe profiles—even shifting them toward patterns of disease—in a matter of days.

Eliminating gluten is no exception. “Our bugs change when we go gluten free,” Murray says. A recent study published in the journal PLOS ONE found that feeding mice a gluten-free diet indeed altered their microbiota. In humans, notes Leffler, a diet-induced shift in microbe populations could increase or even trigger a food sensitivity. “It may be that some diets modulate gastrointestinal symptoms because the type of food you eat modulates your microflora, and not because of the food directly,” he says.

Just how probiotics can reduce symptoms or gluten sensitivity itself is still a guessing game, even for some of the top physicians and researchers. In his own practice, Leffler has found that probiotics improve some patients’ symptoms, but there is no telling which patients will benefit and which strains of probiotics will work. “A lot of trial and error—there’s no way around that right now,” he says.

Probiotic growth for gluten-free, with cautions

As probiotic products grow out of specialty stores and into mass retailers, it is also a time of challenge for makers, says Jeff Brams, general counsel and vice president of international for Garden of Life. “When the trend proliferates, you lose some of the science and premium quality,” he says. “The more choices there are, the more people start to compete on price and convenience. We’re concerned right now, to be frank, that things that have ‘probiotic’ on the label might not be as effective. If consumers start to take something that doesn’t work, that’s not good for any of us.”

One of the largest challenges in creating effective probiotics for any application is the fact that bacteria are an extraordinarily diverse group—much more so than types of wheat grass powder or forms of vitamin D. And we are still far from being able to prescribe particular species, numbers of organisms or dose duration for most health issues, making formulation still, to a large extent, an art as much as a science.

The roles of probiotic products in the gluten-sensitive market could be large—and varied. As research develops, Leffler suspects that we will zero in on bugs that are not necessarily breaking down the gluten itself but rather modulating gut response or the immune system. He foresees a focus on strains that “are doing something to make the gut a little more tolerant.” And some manufacturers are already expanding beyond microbes to help consumers process gluten, says Brams. His company’s Herbal Immune Balance line incorporates both digestive enzymes and probiotics, along with extra nutrients that might lag in a gluten-free diet,
he says.

As complementary supplements, prebiotics could also play an important role in boosting gut health for those going gluten free, Murray says. “If you’re taking a lot of wheat out of the diet, you’re reducing the materials available for good, fermenting bugs in the colon,” he notes. “You need to think about replacing them.”

Consumer concerns

A core group of about 1 percent of the U.S. population must avoid gluten because of celiac disease. “They’re not trending or trying it out,” Murray says. (In some countries, such as Sweden and Finland, some 2 percent of the population has celiac disease, he notes.) In many cases, however, consumers may simply be curious about trying the diet. Comite says many patients come to her saying, “I’m hearing a lot about gluten.” In fact, as of early 2013, about one-third of all adults in the U.S. were trying to reduce or remove gluten from their diet, according to The NDP Group’s Dieting Monitor.

Among all of these populations, “more and more patients are coming in asking about probiotics,” says Melinda Dennis, a registered dietitian and nutritional coordinator for the Celiac Center at Beth Israel Deaconess Medical Center. They aren’t usually using the words “microbiome” or “microbiota,” she says, but “more people are interested in: ‘How are my gut bacteria responding?’ ‘Is there something I should be doing?’”

In her practice, Dennis attempts to alleviate gluten-sensitivity symptoms by turning to “anything I can use to heal the gut and restore it to its proper functioning order,” she says. That can include probiotics as well as vitamins, omega-3s, calcium and digestive enzymes (not to break apart gluten but to handle other symptoms, such a bloating). Her first choice is usually food based—kefir instead of probiotic pills or asparagus instead of prebiotic powders. “Some people do not want to take a ‘medication,’ and they would call [supplements] a medication,” says Dennis, who is also the author of the book Real Life with Celiac Disease. Additionally, she says, consumers want to know that the supplement itself is gluten free and—if they are troubled by other food sensitivities—that pills are made without other potential irritants, such as fructose, soy or corn.

Future of microbiome treatments for gluten sensitivity

The huge growth of gluten free also carries risk. “There’s a lot of hype about gluten-free diets. There are a lot of promises,” Murray says. “And if those promises are not fulfilled, there is going to be swing-back the other way.” But he sees one key way to keep the momentum. “The big challenge for gluten-free suppliers is to make something that’s healthy,” Murray says. “The way this trend will be going will be gluten free and healthy.” And probiotics will likely play a role in that move, whether they come in the form of food—such as kefir or a probiotic-fortified cheese—or in a pill.

Gluten as a sole point of sensitivity might also be challenged as new research and different dietary approaches emerge. Gluten sensitivity could, for many people, be a mislabeling of challenges like fructose malabsorption or overgrowth of bacteria in the small intestine, says Dennis.

The recent emergence and popularity of the low-FODMAP diet—reducing foods with fermentable oligo-, di-, monosaccharides and polyols—has raised the question for many patients and researchers alike: Is it gluten or is it FODMAPs?

For any of these diets, Murray says, given the early days of the research, “if it doesn’t work, don’t keep at it. It is a significant change—it’s not necessarily a healthy diet.” The low-FODMAP diet, for example, is low in fiber and can starve some of the good bugs that live in the gut.

For the time being, probiotics have an edge over traditional medical treatments. They can move quickly to market, not requiring the FDA approval that pharmaceuticals and invasive procedures do. That can come in handy for physicians and consumers, “especially when we don’t have a whole lot else to offer,” Leffler notes. But Murray says that lack of FDA approvals could be a double-edged sword: “Consumers have to be aware that the FDA is not really regulating these, that efficacy is not required” to be proven.

And finding that link—between organism and action—will be key. “The next frontier is not just identifying who they are but identifying what they’re doing,” Murray says of gut microbes. And these bugs do not live or act in isolation. The gut “is a community of interacting bacteria. Understanding what that community is doing and how that community is interacting with us is a huge challenge,” he says. Comite agrees that a carefully curated collection of bacteria will likely be essential. “I think it’s naive to assume one strain of bacteria is going to be enough,” she says.  

Despite all of the scientific excitement and market hype, many researchers and doctors also remain realistic. “There will never be a silver bullet probiotic” for gluten sensitivity, Leffler says. “But I think we’ll do a better job of saying this combination of probiotics does a good job of relieving symptoms.”