Microbiome: The More You Know

The more you know, the less you know, according to the experts. And that’s certainly the case with the complex microbiome market. Here’s an update on what we do know, including the latest science and industry terminology, and a look into the future.

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As we learn more about the gut microbiome, one thing is becoming clear: “The more we learn about the gut microbiome,” says Marc Washington, Founder of Muniq, “the more we realize that there remains much more that we don’t know about this complex ecosystem.”

Scientifically speaking, the term “microbiome” is neither new nor unique to the gut. As explained by the International Probiotics Association (IPA) Education and Communication Committee (ECC): “The ‘microbiome’ typically means the microorganisms in a specific defined environment also including the environment. Though the words microbiome and microbiota are sometimes used in the same way, microbiota refers to the microorganisms, including bacteria, archaea, viruses, and eukaryotes, in a specifically defined environment.”

The gut microbiome, however, is what’s most familiar to consumers, and both consumers and industry are coming around to this terminology. “Consumer research and market research show an increased understanding and interest in the microbiome,” says Arianna Fanning, Business Development Manager, Probiotics, for IFF. “Product development has capitalized on the blossoming interest in the microbiome sector, with many new products and applications emerging that have been studied in a microbiome capacity.” Fanning cites Mintel, noting that new product launches with positioning or marketing using the word “microbiome” grew 267% from 2019 to 2020.

“Regardless of which market research organization is cited, the results are the same: Products targeting the human microbiome are big business,” says Nena Dockery, Scientific and Regulatory Manager at Stratum Nutrition. Dockery points to ReportLinker data showing the market is estimated to grow with a CAGR of 23.6% from 2020 to 2027, potentially reaching $1.873 billion USD by 2027, up from $356 million USD in 2019 (1). “Factors such as the increasing incidence of lifestyle diseases, a focus on  human microbiome therapies, and growing technological advancements in metagenomics have certainly prompted a lot of that growth.”

Currently, Dockery adds, the market is segmented into probiotics, foods, prebiotics, medical foods, diagnostic devices, drugs, and supplements. “Probiotics continue to dominate, with 24.73% of the human microbiome market, and that trend should continue through at least 2027 because of increasing health concerns and the growing awareness of the importance of nutrition and health. But that is evolving as pharmaceutical companies get more interested in the possibilities of drug development, adding another level of complexity to the microbiome market.”

For probiotics specifically, the IPA ECC notes that probiotic consumption had a world retail value of U.S. $44.8 billion in 2019, with forecasted growth to $70 billion by 2025 in probiotic supplements, yogurt, and sour milk products.

As the market grows, research is pouring in. “The National Institutes of Health (NIH) invested 215 million USD in the Human Microbiome Project,” Dockery says. “The European Commission established Metagenomics of the Human Intestinal Tract project to study gut bacteria, which extended into another EU-funded research project, MetaCardis (Metagenomics in Cardiometabolic Diseases), that investigated the role of gut microbes in cardiometabolic diseases. Substantial funding and investments in therapies targeting Clostridioides difficile infection and chronic hepatitis B are other examples of research projects that are expected to influence the growth of the human microbiome market for several years, if not decades. Between 2014 and 2019, Google searches for ‘microbiome’ rose by over 250%; and as consumer research regarding the microbiome has increased, so has product research to satisfy the wants and needs of those consumers.”

 

What have we learned?

All this research has given us plenty to work with. We know, for instance, that many health struggles start with food. “The famous phrase ‘you are what you eat’ is continuously voiced in the health and nutrition sector, but it’s unequivocally true,” says Stephen O’Hara, CEO of OptiBiotix Health. “When our gut microbiome becomes imbalanced, it causes ‘dysbiosis.’ This is where one of more micro-organisms has grown out of proportion to the other bacterial species that inhabit the GI tract, resulting in loss of microbial diversity. The onset of dysbiosis can be prevented by consuming a healthy and balanced diet, or symptoms can either be reversed or aided with an ongoing condition (such as IBS, IBD) by consuming certain prebiotics and probiotics. Clinical trials in this area have since found that the probiotic strain Lactobacillus plantarum can improve gut dysbiosis. Consumers are increasingly becoming interested in this area of health, but as an industry we still have a long journey ahead if we want to collectively make a real impact.”

Dysbiosis can be caused by poor diet—but we know that it can also be caused by medications, by stress, or by illness. And we know that a healthy gut means so much more than healthy digestion. “The emerging science from microbiome research is very exciting,” says Alan Cheung, Executive Director, Belle + Bella. “So far from the NIH studies, they show that our microbiome communicates with and controls many functions of our body. For example, they found our lungs, liver, and kidneys are all in communication with our microbiome. It will be interesting to see exactly how our microbiome communicates with and controls other parts of our bodies.”

In line with this growing understanding, condition-specific products are growing. “Consumer awareness of how a healthy microbiome can affect mental health, body weight, skin health, immune health, and other health issues is growing,” says Amy Kosowski, M.S., LDN, Senior Scientist, Regulatory, and Patent Specialist for NOW. “New probiotic strains are being clinically tested and marketed for specific health issues, instead of for general digestive and immune health claims.”

Some areas being studied:

Gut-Brain Axis. While an area of interest pre-pandemic, during the pandemic this axis took off. Sid Shastri, M.Sc., Director of Product Development, Kaneka Probiotics, tells WholeFoods: “The trends for microbiome online search terms are very clearly illustrated in a recent review by Lumina Intelligence from May 2021, indicating that ‘probiotics and anxiety’ keywords are seeing a dramatic spike. While there was a decrease in search volume between April 2019 and April 2020 of 20%, searches regarding probiotics and the gut-brain axis have grown 50% in the last year. This is likely attributable to the stresses of the pandemic and associated effects like lockdowns and the lack of human interaction.” One example Shastri points to: “The keyword phrase ‘best probiotic for anxiety’ grew 85% year-over-year.”

As of late May, Shastri notes, the Centers for Disease Control and Prevention reported that 45% of Americans were fully vaccinated. “It is a natural sequence for people to pull back a little from immunity concerns, so that they can tend to topics related to the mind such as anxiety and cognitive improvement,” Shastri says. “This is confirmed by Google search trends in the U.S., which indicate that search terms ‘probiotics and mood’ has nearly double the interest of ‘probiotics and immunity.’” Kaneka offers Floradapt L. plantarum DR7, which Shastri says upregulates the tryptophan-serotonin pathway. DR7 was shown in a study to lower symptoms of stress and anxiety.

Nor is that the only strain shown to support this connection: HealthAid America offers MoodProbio, which contains multiple strains which may act as neuroprotective agents and may increase tryptophan production, according to its website.

OptiBiotix, too, is looking to do more in this field. “We have already shown that SlimBiome can impact mood,” O’Hara explains, “and there is also anecdotal evidence from users of LPLDL for improved mood, amongst other health benefits. The potential opportunity and previous demonstratable evidence has meant that we can explore a more substantive investigation in sleep, anxiety and stress with key opinion leaders in the field.”

For more on this, head to www.NaturallyInformed.net and register to view the Mental Wellness: Mastering the Market conference on demand—Uma Naidoo, M.D., gave a keynote speech describing her work as a nutritional psychiatrist, in which she works to alleviate mental illness in part through diet.

Gut-Heart Connection. While other connections may be making their way into public knowledge, this one may be less well-known—but OptiBiotix is looking into it. “We know the latest research tying gut health and cardiovascular disease (CVD) is becoming much more evidence-based,” O’Hara says. “For instance, certain plant-based foods can increase the presence of gut microbes that are associated with a lower risk of developing conditions like obesity, type 2 diabetes, and CVD. These results were recorded by an international study, which investigated more than 1,000 individuals’ gut microbiome composition to discover that certain microbes inhabiting the gut are linked to biomarkers of metabolic disease.”

Additionally, O’Hara notes, “U.S. researchers have used data from the American Gut Project to analyze the microbial composition of stool samples with machine learning technology. On analyzing nearly 1,000 samples, of which half were from people that had CVD, they observed ‘significant differences in gut microbiota between the CVD and non-CVD subjects.’”

While those links are interesting, they can’t prove cause and effect. OptiBiotix’s Lactobacillus
plantarum
, branded LPLDL, however, has been shown in randomized, placebo-controlled human trials to lower LDL cholesterol by up to 13.9% and lower systolic blood pressure by 5.1%, providing evidence of a causative relationship. It was selected from more than 4,000 microbial candidates due to its high bile salt hydrolase enzymatic activity, necessary for its mechanism of action in reducing blood cholesterol.

Gut-Immune Connection. Given that a vast chunk of the immune system lies in the gut, this one will come as no surprise. Here’s an overview of some of the latest studies in this area:

Deerland’s Bacillus subtilis DE111 has been the subject of three published clinical trials within the past 14 months, according to Sam Michini, VP, Marketing & Strategy, Deerland Probiotics & Enzymes. One, published in the International Journal of Molecular Sciences, was performed on 44 healthy adults. The double-blind, placebo-controlled study showed an increase in anti-inflammatory immune cell populations over the course of four weeks in the subjects that took DE111; the study also showed that it promoted anti-stress pathways by suppressing pro-inflammatory agents. Two studies were performed in children, one published in Journal of Probiotics & Health and one in Beneficial Microbes. The first study found that children taking DE111 showed a statistically significant improvement in symptoms such as vomiting, discomfort, and incidence of lower GI infections; the second study suggested that children who took DE111 had an expanded functional diversity of the microbiome, compared to children in the placebo group.

Researchers have also linked an increase in Bifidobacteria with a lower incidence of infections in a study with 219 kindergarten children, according to Anke Sentko, VP of Regulatory Affairs & Nutrition Communication, BENEO. Still another study, she says, demonstrated that consuming formula enriched with Orafti Synergy1—Beneo’s branded oligofructose-enriched inulin—shortened infection episodes for infants, and lowered daily crying time.

Catering to children, AIDP offers a line of probiotics under the Hereditum brand, according to Samantha Ford, MS, Director of Business Development at AIDP, who explains: “Hereditum is a range of premium probiotics isolated from human breast milk supporting immunity in children and adults and infant colic. Hereditum is one of the most widely studied ranges of probiotics, with more than 30 publications in prestigious scientific journals. It can modulate human immune defenses, reducing the risk of infections and alleviating inflammatory responses in several chronic inflammatory conditions.”

Gut-Skin Connection. “We recently noticed an uptick in sales on our beauty-from-within prebiotic, BeautyOLIGO,” said Ford. “Consumer awareness around the gut-skin connection is growing.”

What is the gut-skin connection? Ford explains: “The gut acts as a major line of defense for the rest of the body. An imbalanced gut environment can lead to suboptimal function of the intestinal barrier. As a result, unwanted toxins can be produced, absorbed into the bloodstream, and accumulated in the skin. This can cause inflammation, degradation of collagen and elastin, and unhealthy skin appearance.”

BeautyOLIGO, Ford explains, is a prebiotic backed by clinical studies that have shown the ingredient can positively affect skin. “According to a recent study,” Ford said, “BeautyOLIGO helps to optimize the gut environment by stimulating the growth of beneficial bacteria and hindering the growth of harmful bacteria. In turn, it helps strengthen the immune system, helps to eliminate toxins, and inhibits the activation of collagen- and elastin-degrading enzymes. In human clinical research, BeautyOLIGO reduced the appearance of fine lines and wrinkles with daily supplementation.”

Permanent vs. Transient

There’s an argument against the use of many probiotics that states that, if the probiotic in question doesn’t permanently take up residence in the gut, it isn’t useful. However, it’s rapidly becoming clear that there are plenty of ways to affect the gut without directly permanently altering it. Belle + Bella’s Cheung argues that it’s not even necessary for probiotics themselves to be permanent: “So currently, most probiotic supplements on the market use transient probiotic strains, but the good news is, research has shown that it still can affect our microbiome positively.” The ideal of permanence, Cheung says, is not an evidence-based standard to which probiotics must be held.

Justin Green, Ph.D., Director of Scientific Affairs, Cargill,  points to pre- and postbiotics as further proof that ‘transient’ does not mean ‘useless.’ “One of the developments in this field is the concept that nutrients in foods or supplements do not need to be absorbed in the upper gastrointestinal tract to have a beneficial health impact, but rather can interact with the gut or gut lining to cause a benefit. Some examples include affecting the microbiota—whether by adding to it with probiotics or modulating it with prebiotics—to strengthen the many roles the microbiota already plays.”

And along the same lines, ‘alive versus dead’ is no longer necessarily a useful argument—strengthening the idea that bacteria doesn’t have to be introduced into the gut and thrive there in order for -biotics to be useful. “The body of evidence is increasing that shows that ‘dead’ microbes are effective in generating many of the health benefits that are seen with live probiotics,” said Dr. Green. “This has big ramifications on product development, because these postbiotics are inherently easier to keep stable during processing and storage, as they do not need to be kept alive.”

The Latest in -Biotics

Probiotics continue to grow, as outlined above by the IPA ECC; meanwhile, however, prebiotics, postbiotics, and synbiotics are taking some major steps:

Prebiotics. Those who know about prebiotics may have a very specific understanding of it, one which needs to be broadened, argues Len Monheit, CEO, Trust Transparency Center, and Executive Director, Global Prebiotic Association. “There are misinformation and perceptions that need to be challenged lest they take deeper root, such as the limiting belief that all prebiotics do is feed gut bacteria, when evidence is continuously expanding to support diverse mechanisms and interactions. We’ve got to keep it simple, but we have to tell the story that newer science is showing us.”

AIDP’s Ford adds: “As prebiotics have been on a hockey stick trajectory in terms of growth, we are already seeing these concepts disrupt the market. For example, ‘probiotic-free’ digestive health formulas are becoming more and more popular. Also the concept of food-derived ingredients that can selectively alter the microbiome, as would happen with the consumption of more whole, plant-based foods, is appealing to the consumer in the era of clean-label, functional ingredients. AIDP offers a resistant starch based on green bananas, as well as our line of kiwi-based prebiotics.”

There’s also some non-fiber prebiotics out there, such as bacteriophages like Deerland’s PreforPro. “PreforPro destabilizes the cell wall of unwanted bacteria, thereby allowing access to nutrients and space that good bacteria can use to grow,” says Michini. “By using phages that target the unwanted bacteria in the gut, PreforPro has been shown to modulate the gut microbiota and encourage the balance of good bacteria over bad. With the unwanted bacteria at a disadvantage, healthy bacteria have room to take up residents in the gut and flourish. This results in better digestion and immune support.” PreforPro is supported by a 2019 study published in Nutrients, which showed that consuming 15mg of the blend daily for 28 days augmented quality of several species, and reduced circulating levels of the pro-inflammatory cytokine Il-4.

Postbiotics. Over the past couple years, WholeFoods features on the microbiome have documented this category’s growth. It recently took a major step forward, in that it has now been defined for the industry by the International Scientific Association for Probiotics and Prebiotics (ISAPP), which published a consensus statement on the definition and scope of postbiotics in the journal Nature Reviews Gastroenterology & Hepatology. The definition—which was shared early with attendees at the #NaturallyInformed event Driving Opportunities in the Microbiome Space, available on-demand—states that postbiotics are “a preparation of inanimate microorganisms and/or their components that confer health benefits on the host.”

“Postbiotics provide several distinct advantages,” Dockery opines. “The microbes—bacteria, yeast, fungi, et cetera—have been treated, usually by heat, so they are no longer living and vulnerable to conditions that affect viability. But extensive research has shown that they still provide the benefits, perhaps even more in some cases, than their ‘living’ counterparts, especially in the postbiotics that also include the cell-free supernatant—the nutrient broth in which the microbes are fermented, which contains the byproducts of microbial metabolism.”

From a formulation perspective, Dockery says, the advantages keep racking up: “Since postbiotics are not alive, they are not susceptible to die-off, which is one of the biggest challenges in manufacturing probiotics from human-derived strains. As a result, postbiotics can be formulated into multiple dosage formats, such as conventional foods, gummies, chews and even beverages. Postbiotics are also gastric stable and can survive transit through the highly acidic environment of the stomach. Furthermore, they can’t translocate across the intestinal wall as live microbes in vulnerable individuals.”

There are already ingredients that fit the definition. One: Stratum’s LBiome. “This postbiotic has been in existence and researched in Europe since the early 1900’s,” Dockery says. “It is a premier postbiotic for digestive health, with an extensive portfolio of research in both children and adults. LBiome is a blend of two human-derived bacterial strains, Lactobacillus delbrueckii and Limosilactobacillus fermentum, both already recognized for their beneficial role as probiotics.”

Another: EpiCor, an ingredient made by Cargill. It fits the first half of the definition by being made up of the metabolites of fermented baker’s yeast, according to Cashtyn Lovan, Marketing Manager at Cargill. As to the second half of the definition, Lovan said: “Over a dozen published studies, including multiple human clinical trials, show that EpiCor postbiotic supports the gut microbiome, immune health, and nasal comfort.”

Cargill is investing in education on this topic, Lovan says. “We have created videos and infographics that help explain what postbiotics are, how they are beneficial, and what makes them different from pre- and probiotics.” These resources are available at www.epicorimmune.com.

Synbiotics. “From a market perspective, the latest is the continued development of synbiotics, that is, the combination of prebiotics and probiotics,” asserts TTC’s Len Monheit.

Hannah Ackermann, RD, Corporate Communications Manager at Comet Bio, seconds that. “Given the symbiotic relationship between probiotics and prebiotics, it is not surprising that synbiotic products are emerging as the next big trend. Besides providing consumers with a more complete gut health regimen option, supplying prebiotic and probiotics in tandem is thought to help improve the activity of beneficial microorganisms in the gut. In simpler terms, providing probiotic bacteria with a prebiotic gives the bacteria a better chance of surviving and thus positively impacting the microbiome.”

However, she notes that this isn’t as easy as tossing a pre- and a pro- together. “Synbiotics do present a complex formulation challenge. Manufacturers must be careful in choosing the right probiotic strains and prebiotics to combine. To truly be a synbiotic product, the prebiotic presence must improve the probiotic’s survival and ability to colonize in the microbiome. Simply combining any prebiotic and probiotic does not necessarily create a true synbiotic.”

Wakunaga, for instance, now offers Kyo-Dophilus Pro+ Synbiotic, which contains nine probiotic strains and the branded prebiotic BioEcolians, noting on its website that the prebiotic is “specially selected” to feed good bacteria, such as the strains included in the product.

Ingestibles

Besides kombucha, there’s plenty of opportunity for functional foods. Part of what the Beneo Institute does, for instance, is provide information to food and beverage manufacturers looking to add prebiotic functionality to their products.

Comet Bio’s Hannah Ackermann says that this category is one that’s showing growth. “Rather than taking a supplement,” she said, “many consumers are turning to a new category of beverages, confectionery, snacks, and baked goods, known as ‘healthy indulgence’ or ‘permissible indulgence.’ These products are better-tasting than supplements, and can be easily incorporated into existing routines.” Another area where she sees brands making moves: coffee. “Coffee is a quintessential part of many consumers’ daily routine. Adding functional ingredients, such as prebiotic fiber or collagen, into coffee formulations allows consumers to incorporate the supplements into their existing daily routine more easily.” She points to Comet Bio’s Arrabina prebiotic fiber, a fully soluble powder which she says “complements coffee’s natural flavor and color profile.”

Part of what this may involve, Ackermann projects, is a class of prebiotic fibers that are effective at lower doses than inulin’s 5g/day, with better tolerability. She notes that Arrabina is well-tolerated even at high doses, and effective at 3.4g/day.

5 Challenges… and Opportunities

We asked the experts, and they listed out the trials they face—and identified the opportunities inherent to those challenges. Those challenges fell into five categories:

1. Delivery format updates. Michini foresees more diversity in delivery format. “Probiotics and prebiotic manufacturing technology have moved beyond encapsulated products,” he asserts. “This venerable delivery system, of course, remains an excellent, viable choice for those who prefer it. Gummies are perceived as a break from pill overload, and as a treat. Meanwhile, stick packs are viewed as the opportunity to enjoy a beverage whose flavor intensity can be controlled through the amount of liquid added. Consumers are more likely, however, to equate gummies with vitamins and some condition-specific supplements such as immune support—but not so much with probiotics. They are likely to view stick packs in much the same way.” His suggestion: “Bring the spotlight onto capsule alternatives. Many of our customers do provide microbiome-nourishing probiotics and prebiotics in non-capsule, consumer-friendly—and kid-friendly—delivery forms.”

Different formats are taking off already in children’s products, as Michini mentioned, such as Wakunaga’s Kyo-Dophilus Kids Probiotic, which comes in a chewable tablet. HealthAid America, too, offers a chewable KidzProbio, and a liquid product, Infant Probio, which provides a strain isolated from breast milk, to support infant health.

2. Education for all. The science in this area is evolving constantly; as such, education on all fronts is necessary. “In the early days of the probiotics business,” Cheung recalls, “consumers looked at us funny because we were trying to sell them bacteria. We were still getting that same ‘look’ from consumers as recently as the early- to mid-2000s. Consumers are just now starting to recognize the benefits of probiotics. Hopefully, as consumers get more educated about the benefits of probiotics, they will have an easier time understanding the relationship to the microbiome and its function.”

Muniq’s Washington seconds this. “One of the biggest challenges in this area is bridging the gap between the advancements in scientific progress and the lack of consumer awareness and understanding of the vast potential of the gut microbiome. The majority of consumers are only vaguely aware of the importance of the gut or around ways to positively impact it. At best, most associate gut health with digestive health without understanding its much broader implications on overall health. This makes it challenging to educate consumers and motivate them to seek out products that they desperately need which could be potentially life-changing, but don’t know anything about.”

That challenge is already on its way out, according to Sentko. “The importance that a healthy microbiome plays for overall health and well-being is top of mind for consumers,” she says. “A recent Health Focus International study (2020) found that of those surveyed, 42% were ‘very or extremely interested in the gut microbiome.’ Consumers are aware of fiber and its contribution to creating improvement in the digestive tract, bringing benefits like a healthy gut bacteria environment, increased immunity, regularity, and healthy weight and blood sugar management. In particular, consumers are beginning to understand that a balanced microbiome can positively affect the entire body and they are aware that ‘what happens in the belly doesn’t stay in the belly.’” Beneo’s Orafti inulin and oligofructose have been shown in clinical studies to increase Bifidobacteria.

Ackermann agrees. “Linkage Research & Consulting Inc. reports that 87% of Americans understand that there is a connection between digestion and health, and 70% say they are proactive about their digestive health. In addition, awareness of prebiotics has grown to 81%, with 35% of supplement users taking prebiotics at some level, according to Ingredient Transparency Center (ITC) Insights’ 2020 Consumer Survey. There are a clear consumer interest and demand for gut-healthy and fiber-rich products.” Comet Bio’s Arrabina arabinoxylan prebiotic fiber has been shown in clinical trials to promote beneficial bacteria growth.

The next arena, according to the IPA ECC, is regulatory and healthcare professionals. “IPA continues to expand probiotic communication outreach and education of regulatory bodies, and translation of science into evidence-based practice for health care professionals to use with their consumers to dispel misinformation, myths, and inaccuracies. IPA strives to educate Physicians, Pharmacists, Dietitians, Naturopaths and Integrative Health Practitioners and Consumers. Many Health Practitioners indicate their interest in probiotics is extremely high, and they strive to meet probiotic education needs of their patients.” This education will continue, the ECC feels, as more research is conducted in areas including the gut-brain axis, skin health, and oral health.

Beneo is working to bring the latest science to the forefront and looking to provide more still. Sentko points to the Beneo Institute, which provides access to the “latest nutrition science and innovations,” and takes part in research and international conferences. The goal: to support health professionals and food and drink manufacturers.

In all of this, retailers haven’t been forgotten. The Council for Responsible Nutrition (CRN) has created the “Probiotics: What’s Inside is Alive” campaign, intended to provide retailers with information about labeling practices, storage and handling requirements, and health benefits. The goals: helping retail buyers better curate their offerings, improving retailer handling of probiotics, and informing customers about the benefits of these products.

In a press release on the topic, Andrea Wong, Ph.D., SVP of Scientific and Regulatory Affairs at CRN, said: “As these live organisms continue to grow in popularity, CRN will expand educational resources for the retail community to ensure consumers have access to high quality and beneficial probiotics.” More information can be found at www.crnusa.org/probiotics.

3. Linguistic & regulatory updates. Language and regulation are all tied up, and changing as we speak. On the marketing side, Michini says that major industry terms are evolving. “’Flora’ has been used for quite some time, but ‘microbiome’ and ‘microbiota’ are more precise and easier to convey in a cogent manner. Here, the challenge is to fully replace outdated language and use the terms ‘microbiome’ and ‘microbiota’ correctly. We believe that when most consumers understand the language, they can seek out the most suitable probiotic/prebiotic products.”

On a regulatory side, many terms don’t have a regulatory definition. “While there is a WHO definition of probiotic, there is none for either prebiotics or postbiotics,” explains Monheit. “And even with probiotics, it is only recently that EFSA in Europe has allowed the use of the term on the label. There is need for ongoing dialogue with regulators, to ensure the proper regulatory environment for foods versus supplements,
as appropriate.”

On top of that, when there is a regulatory definition, that doesn’t necessarily mean that marketers are in the clear. Kosowski notes that “FDA recently redefined the term ‘fiber’ to include mostly only fibers that are intrinsic to foods, with some notable exceptions. This has forced some relabeling of ‘fiber’ products as ‘prebiotics,’ which may actually help the prebiotics category grow faster, as the reeducation of consumers regarding the benefits or prebiotics is necessary to market these products effectively.”

There’s also the challenge of bringing new products to market, while clearing regulatory hurdles. “Newer probiotic strains may require filing of an NDI notification with FDA to enter the market,” says Kosowski. “This requires time and money, so truly innovative ingredients will be slower to market. Strain-specific claims can only be developed in response to published literature, as clinical studies are needed to substantiate these claims. As long as there is funding for this research, more and more strains will become available for customers.”

It’ll be a slow drip, though, according to Trevor Wagner, Ph.D., Business Development Manager, Probiotics, for IFF Health. “In general, the challenges that are faced in this area are how to provide customers with the highest quality scientifically supported ingredients that provide health benefits that consumers care about and realize. In terms of probiotics, one of the main challenges is how to take novel microorganisms newly identified from the microbiota and successfully navigate the regulatory environment to bring consumers exciting new products that uniquely benefit their health.”

That said, IFF’s Fanning notes that the market is getting increasingly crowded, making it increasingly worth it to put in the time and money to bring a unique, stand-out product to shelves.

Other regulatory challenges: Labeling. “FDA regulations require most dietary supplement products to contain over 90% of their activity content at end of shelf-life,” Dockery explains. “When probiotics are declared by milligram weight, this is not an issue, but when declared more accurately by colony forming units, it can be challenging because of losses in CFU counts during storage. This may become more of an issue as regulatory bodies move toward a requirement that CFU counts reflect the live bacterial counts at end of shelf-life.” Here, Dockery says, companies are looking for opportunities outside of the traditional Lactobacillus: “The use of spore-forming bacteria as probiotics provides more opportunities for product development, because of their survivability in a much broader range of conditions.”

And for a regulatory challenge that hasn’t even hit yet: “I believe in the coming years we will continue to see the emergence of natural, nutritional products that work through your gut microbiome which have the potential to fundamentally impact human health,” opines Muniq’s Washington. “This has potential to make the adage about using ‘food as medicine’ quite literal, which could push the traditional regulatory boundaries as to what defines ‘food,’ versus functional/medicinal foods, versus therapeutics.” And the opportunities there remain to be seen.

4. Personalization. “We believe the future of microbiome research will be in custom/personal supplement formulations,” says Cheung. “To be able to determine the specific needs of an individual, based on their microbiome. About 10 years ago, we started focusing on targeted use formulas for our Probiology probiotics supplements, which included clinically studied probiotic strains that have shown effectiveness for those specific uses. We are confident as additional science emerges from the NIH study of the microbiome that we will be able to further narrow the scope of our targeted probiotic formulas to bring the maximum efficacy to an individual’s microbiome.”

The industry is already looking to solve this challenge. “Microbiome analysis is becoming more available and accessible, which should become the basis for a more personalized supplementation strategy for consumers,” says Kosowski. “Probiotics will continue to be popular, but prebiotics and postbiotic products will grow as well, as soon as consumer understanding catches up with current scientific research. Educational efforts continue with each new product release, but NOW also currently posts numerous educational articles on our website to help consumers understand the scientific basis of the benefits of our products.”

O’Hara points to advancements in 3D technology that can help, here. “Researchers at Tufts University in Massachusetts have created the first non-invasive diagnostic tool, which can provide a profile of bacterial microbe populations throughout the entire GI tract. Covered with a pH sensitive coating, the pill does not absorb any samples until it enters the small intestine where the coating eventually dissolves. This research means we are now coming much closer to discovering why certain people from different backgrounds and cultures adopting specific dietary lifestyles are more prone to specific chronic diseases. However, there is still much to learn in this field. At OptiBiotix, we are funding several different research projects to understand how our own products can help reduce the risk of
preventable conditions.”

5. Understanding of the microbiome itself. For all that we’re well on our way to personalized microbiome supplements, the experts tell WholeFoods that, actually, we don’t understand very much, yet. “The organisms contributing to the microbiome are a vast resource that will continue to be the source of new discoveries for the forseeable future, that could include yet unknown mechanisms and microorganisms that benefit human health in ways that are not currently imagined,” said Dr. Wagner. “IFF has initiated efforts like the Human Microbiome Venture, dedicated research resources, and spearheaded joint developments, all with the goal of realizing these discoveries and bringing them to our consumers.”

Ackermann, too, feels that there’s still a long way to go. “The microbiome was only fully mapped a few years ago,” she says, “and scientists are continuing to learn more about how the gut microbiome can affects overall health. One area of particular interest is how the gut microbiome can affect brain health. This connection, the gut-brain axis, could lead to more insights into how tweaking the microbiome could prevent or treat cognitive and autoimmune diseases. Investing in clinical trials is pivotal to better understanding this link. But the science around the microbiome is still in its infancy.” WF