The panel:

Denis Alimonti, Director of U.S. Nutrition, Maypro, Purchase, NY, www.maypro.com

Rob Brewster, President, Ingredients by Nature, Montclair, CA, https://ingredientsbynature.com

Melanie Bush, Vice President of Science and Research, Artemis International, Fort Wayne, IN, https://artemis-nutraceuticals.com

Anurag Pande, PhD, Vice President Scientific Affairs, Sabinsa, East Windsor, NJ, https://sabinsa.com

Jordi Riera, Chief Business Officer, Kaneka Probiotics, Pasadena, TX, https://kanekaprobiotics.com

Chris Sadewasser, Global Product Manager, Kemin Human Nutrition and Health, Des Moines, IA, www.kemin.com

Antonio Vendrell, Marketing Director, Bioiberica, Barcelona, Spain, www.bioiberica.com

Mark Walin, Senior Vice President of Business Development & Marketing, BIO-CAT, Troy, VA, www.bio-cat.com

The demand for ingredients and finished products that support digestion and gut health is large and growing, and it’s driven by a multitude of factors, including: a rapidly aging U.S. population; increasing numbers of consumers with chronic gastrointestinal issues; and greater awareness of such categories as probiotics and of gut health and the microbiome, more broadly.

Here to help us sort it all out is a panel of industry experts.

NIE: Describe the current market for ingredients and products geared to digestive health, gut health or both.

Alimonti: With the digestive health market clocking in at over $44 billion in 2022 and with microbiome-support ingredients estimated to grow as much as 10 percent through 2029, it’s a competitive landscape.

Maypro fortunately offers a range of clinically validated ingredients for digestive and gut health that provide formulators and product developers with solutions for a variety of indications and the necessary stability for development and efficacy.

Brewster: Enzymes and all ‘biotics (pre-, pro-, post-, synbiotics) are the top ingredients consumers are familiar with when it comes to gut and digestive health. As a formulator of custom pre-and probiotic-based formulations and blends for over 50 years, we can confirm that this sector has seen exponential growth over the past five years.

Bush: Savvy consumers are connecting the dots between gut health, immune health and brain health more than ever before, which is fueling a product development frenzy on the brand side. What used to be a yogurt market has exploded into capsules, gummies, beverages and more. Fermentation, once mysterious, is now better understood and has opened the door to even more product development.

Walin: What we’re seeing in the digestive health marketplace now is a shift from standalone ingredient formulations to multi-ingredient supplements that combine botanicals and biotics for long-term benefits and enzymes for tangible, short-term benefits.

The synergy between probiotics and enzymes is especially intuitive when we appreciate that probiotics work, in part, due to their own production and release of digestive enzymes into the gut. Ultimately, supplemental microbial enzymes help break down food and dietary fiber, enhance nutrient availability, and help reduce occasional gas and bloating.

Sadewasser: According to FMCG Gurus, 79 percent of consumers worldwide recognize the link between their immune and gastrointestinal health. Thus consumers are starting to seek out products that not only help their digestive/gut health, but they are looking for ones that help beyond the gut for overall health and wellness.

Vendrell: We’ve only scratched the surface of innovation in the digestive health market. A key sector in the wider dietary supplements arena, it has a market share of almost 8 percent. That makes it the fourth biggest market after energy and weight management, general health, and bone/joint health.

It holds huge potential for several reasons. Firstly, there is an increasing awareness of the interconnection between gut health and overall wellness, as well as an emerging knowledge of how to modulate the gut microbiome to unlock its digestive—and wider—health benefits. This unfolding wisdom is paving the way for a multitude of exciting opportunities in the field. At the same time, there has been an evident rise in digestive health concerns worldwide linked to aging, unhealthy dietary habits, lifestyle choices and improved diagnostic technologies.

NIE: Early in the 20th century, health products for digestion mainly consisted of bitters and digestive tonics. What sub-categories or types of ingredients are the biggest today, and why?

Riera: Our understanding of digestive health has evolved, and so has the range of ingredients and products available in the market. These products include probiotics to enrich the gut microbiota, prebiotics to promote the growth of probiotics, postbiotics and their metabolic byproducts. As the science in this area of gut health has progressed, there is now clinical research to substantiate the benefits of clinically tested products.

Walin: While products and categories may have changed over the past 100 years, the one thing that hasn’t changed is the consumer’s concern over their digestive wellness. One example is the $2.8 billion PPI (proton pump inhibitor) OTC (over-the-counter) category. PPI use can reduce digestive acid hydrolysis, artificially elevating stomach pH—potentially contributing to digestive issues.

BIO-CAT believes that the best type of ingredient to compensate for concerns like incomplete digestion from PPI use is enzyme supplementation. Digestive enzymes are proteins whose specific function is to break down macronutrients into smaller parts that can be absorbed. The market is poised for growth where products with substantiated science can deliver on claims.

Sadewasser: Today, we are starting to see the introduction of postbiotics into the digestive health category. Kemin offers BetaVia, a postbiotic, sourced from a proprietary beta 1,3 glucan that supports your immune health by supporting intestinal barrier integrity and a healthy microbiome.

Beyond the biotics, we also see botanicals, short chain fatty acids and digestive enzymes commonly used in the space. Kemin recently launched ButiShield, an encapsulated source of calcium butyrate that provides a controlled and sustained release in the gut of butyric acid. Produced using Kemin’s MicroPEARLS technology, ButiShield offers a low odor encapsulate to ease formulation and handling.

Alimonti: Old-school products like those were intended to stimulate salivation or digestion, whereas gut-health products today are more about supporting microbial balance and the health of intestinal mucosa.

Today’s gut health products are evolving rapidly as our understanding of the gut-brain axis increases. From cognitive health to oral health and skin health to weight management, biotics are giving us a wide variety of indications to address.

NIE: A common misconception is that in “the old times” people ate better but, in fact, old-time American diets were packed with lard and bereft of most vegetables. What are the eating patterns that are the primary contributors to today’s “epidemics” of microbiome imbalance and digestive unhealth?

Pande: Processed food wreaks havoc on the microbiome and digestive health. We are overfed and undernourished. Processed foods lack essential nutrients and, while they pack a good amount of calories, they fail miserably in simple ingredients like fiber. Fast food and processed food that suit the palette have drastically changed the health of Americans and brought us to widespread microbiome imbalance, as well as conditions like obesity and overweight.

Bush: It all comes down to one thing: sugar. Excessive sugar intake, especially fructose and sucrose, is highly correlated with metabolic diseases, fatty liver and cardiovascular disease. Both hyperglycemia and excessive sugar intake disrupt the intestinal barrier, increasing gut permeability and causing profound gut microbiota dysbiosis, which results in a disturbance in mucosal immunity that enhances infection susceptibility.

Riera: Kaneka Probiotics and AB-Biotic’s development model is based on the known scientific fact that people have lost microbial diversity in their gut flora. These lost bacteria are what we call, “Microbial old friends.”

The depletion of these “microbial old friends” has been linked to the development of synthetic chemicals found in the modern human diet, typically in processed foods. Many of these foods contain fillers, preservatives and artificial ingredients, all of which are detrimental to our gut flora.

We have spent years accumulating samples of different microbiomes in different parts of the world from populations who have preserved a traditional lifestyle. We have excelled in locating and isolating rare and beneficial strains.

Alimonti: While massive consumption of lard is not as common today, fast foods and processed foods do loom large in the U.S. diet, along with gargantuan consumption of sugar, high-fructose corn syrup and a range of nutritionally compromised food and beverage products. All of this contributes to today’s health landscape.

NIE: The market for berry-based supplements and berry/fruit-powder ingredients seems to be growing each month. Why is the market bursting with berries?

Bush: Berries are super popular in formulations for one simple reason: consumers equate them with wellness. In other words, if a formulation contains berries or berry ingredients, there is an immediate perceived health benefit. Period. What’s unfortunate is that many berries are not easy to get in fresh form or may not be particularly palatable. This is where berry ingredients and berry blends can be so beneficial.

Two berries of note, elderberry and aronia berry, fall into this category, especially for gut/digestive health. Neither are available fresh and if they were, they would be too tart or bitter to eat. Our ElderCraft and AroniaCraft extracts are a perfect addition for gut health formulas and formulate well in functional foods, beverages, and gummies.

NIE: As to why a growing number of Americans don’t produce a sufficient quantity of the proper digestive enzymes, it seems there are a number of causes. To what do you attribute today’s digestive enzyme shortfalls?

Vendrell: There are several factors involved, like aging, stress, medical conditions, medications, genetics and more—which are what make conditions linked to enzyme deficiencies so complex to identify and manage.

Take histamine intolerance as an example—a gastrointestinal condition associated with impaired dietary histamine metabolism, whereby histamine is not degraded properly in the body. Histamine intolerance affects up to 3 percent of the total global population—and rising. Yet it remains a largely unaddressed health issue. We want to change that.

Alimonti: A few factors come to mind. For one, most food products are processed in a way that destroys whatever natural enzymes in the foods would help us to digest them. A second point is that the levels of enzymes we have now are appropriate for our ancestral diets thousands of years ago but are not designed for the diets we eat today. Thirdly, since the pancreas in many people is overworked trying to produce insulin to cope with the sugar-saturated diets we have, it’s possible that the modern U.S. diet has compromised this organ’s ability to release digestive enzymes.

Brewster: Research shows that people with glucose intolerance have an unhealthy gut microbiome. Currently, there are approximately 98 million Americans with prediabetes—that’s one in three people, however, nearly 84 percent of them don’t realize they have it. It’s also estimated that 38 million Americans have diabetes. Diabetes is one of the most prevalent and expensive chronic conditions in the U.S., only behind cardiovascular disease and stroke. It accounts for $327 billion—every one in four health care dollars—in the U.S.

Four published clinical trials on our proprietary blend of citrus flavonoids, Eriomin, have shown that improving blood glucose levels, managing a healthy inflammatory response, and receiving strong antioxidant support can drastically improve glucose levels and support normal insulin sensitivity.

Walin: To understand the digestive enzyme shortfall amongst Americans, it helps to understand the dual contributions of human and gut microbial enzymes to digestion. Human “endogenous” enzymes are the digestive proteins encoded by the human genome, like gastric pepsin, which breaks down dietary proteins in the stomach, in addition to pancreatic lipase and amylases that break down dietary fats and carbohydrates, in the small intestine. Unfortunately, clinical observational studies dating back to the 1990s have demonstrated that human enzyme function begins to decline naturally with age when we enter our 40s. So, we can pin some of the digestive enzyme shortfall on aging.

Another major factor, though, is diet. Unfortunately, Americans on the whole do not eat sufficient dietary fiber to maintain robust and diverse gut microbiomes. There is apparently a gut microbial enzyme gap between unhealthy and healthy dietary patterns. This points to the potential of supplementing with oral biotics and microbial enzymes, along with dietary modification, to help bridge the gap to healthier gut microbiomes associated with high-fiber diets.

Pande: Understanding the gut-brain axis has helped us to manage conditions related to irritable bowels as well as managing depressive disorders that are linked to the irritable bowel.

LactoSpore, Sabinsa’s shelf-stable probiotic with patented strain of Bacillus coagulans MTCC 5856, has been clinically studied for managing both these gut-brain axis conditions. In fact, these studies led to approval of health claims in Canada for managing intestinal pain associated with irritable bowel syndrome (IBS) and managing healthy mood.

NIE: Increased understanding of the gut-brain axis has led to what recent advances in product development and innovation?

Sadewasser: With approximately 70 percent of the immune system located in the gut, we are seeing that maintaining good gut health is vital to supporting other areas of our health like our immune health. We are beginning to see products target more aspects of overall health and wellness, with the gut being an area of focus.

Riera: The increased understanding of the gut-brain axis has significantly influenced product development and innovation in the health and wellness industry. Consumers are realizing that there are products which can enhance their brain health and enrich their gut as well. For example, Kaneka Probiotic offers our patented strain L. plantarum DR7 designed for mood and stress support.

Walin: Product innovators are developing products such as probiotics that can affect serotonin production and the neurotransmitter gamma-aminobutyric acid (GABA). For example, BIO-CAT is screening their strain library for Bacillaceae strains that can produce serotonin, dopamine, and noradrenaline. Interestingly, the amount of these biogenic amines produced varies widely between strains.

Alimonti: It has been said that 80 percent of the communication signals between the brain and gut are from the gut to the brain. It’s also been found that supporting the microbiome with probiotics helps with several areas of cognitive and neural health. This is reflected in the development of products that address microbial balance for things like mood support and focus.

NIE: Welcome to the age of biotics! Prebiotics, probiotics, postbiotics and synbiotics—in a nutshell, what tips should manufacturers keep in mind?

Alimonti: Biotics are dynamic and there is a lot to consider. We always emphasize the importance of human clinical trials on multiple populations and age groups with strong stability data. We are particularly excited about the interaction between postbiotics and the immune system and how that impacts the microbiome.

For example, KT-11—a heat-sterilized, proprietary strain of Lactobacillus crispatus—supports oral health by inducing Secretory IgA activity.

L-92—produced from sterilized cells of a proprietary strain of Lactobacillus acidophilus—supports allergic response through the modulation of the Th1–Th2 balance.

LAC-Shield—a strain of heat-killed Lactobacillus paracasei—supports overall immune health by inducing interlukin-2, a type of cytokine that promotes the development of T regulatory cells.

Pande: While some of these subcategories are new, there is one common factor that needs to be looked into before choosing any of these ingredients: the strain.

Information and understanding the relevance of the strain of a bacteria chosen for a probiotic, postbiotic or symbiotic product is the most important part of product development. Bacterial strains of same species may differ in their properties, affecting their performance, stability and even their probiotic benefits.

Science on one strain cannot be extrapolated to another strain, so while choosing the probiotic, symbiotic, or postbiotic, it’s important to know the strain and science on the strain.

NIE: Pick one digestive-health product, and identify what is the latest, and most exciting, study supporting it.

Bush: A recent human clinical study from Reider et al. (2022) found that ElderCraft European Black Elderberry Extract induced profound changes in microbial diversity. It also caused a lasting increase of Akkermansia muciniphila, a particular gut microbe of interest for digestive health. This launches elderberry into a new functional category in addition to its well-known immune support properties.

Brewster: Our proprietary blend of citrus flavonoids branded Eriomin recently demonstrated its ability to produce short-chain fatty acids and help remove the “bad” bacteria for an improved microbiota. The double-blind, placebo-controlled human clinical trial demonstrated that Eriomin improved prediabetes microbiota and could attenuate intestinal dysbiosis with just 200 mg/day after 12 weeks of supplementation. Of additional importance, Eriomin decreased the study volunteers’ fasting blood glucose by 6.5 percent and increased GLP-1 incretin by 22 percent. GLP-1 promotes insulin production and removes glucose from the bloodstream, making this the most critical hormone in helping manage healthy blood glucose levels.

NIE: We know about lactose and gluten intolerance. Now, there are emerging digestive health ingredients that are geared to account for histamine intolerance. Please discuss.

Vendrell: Individuals with histamine intolerance usually present with DAO (diamine oxidase) enzyme deficiency or impaired DAO enzyme functionality (the enzyme responsible for degrading histamine from foods and beverages).

DAO supplementation can help to restore levels of the enzyme in the body, assisting the breakdown of histamine from foods and beverages in the small intestine and alleviating allergy-like effects (such as gastrointestinal issues, sneezing, runny nose or congestion of the nose, headache, abdominal pain, hives, itching, flushing and asthma). The recommended frequency of supplement intake varies from one-to-three times per day, depending on the individual’s sensitivity.

Notably, as well as lowering histamine levels, DAO supplementation does not induce the same negative side effects often experienced with antihistamines—like drowsiness, dry mouth and eyes, dizziness and headaches. With this in mind, DAO-based solutions are creating new opportunities to diversify product offerings and craft formulations that go beyond merely relieving the allergy-like effects to actively aiding histamine digestion.

Bioiberica’s DAOgest is a premium digestive health ingredient providing a high-quality DAO enzyme to manage histamine digestion. It is effective at a dose of 4.2 mg per serving.

Walin: BIO-CAT has focused its research and product development on the largest segments impacting the greatest number of U.S. consumers. These segments are led by lactose (12 percent), non-celiac gluten sensitivity (6 percent), closely followed by bean/legume. Histamine intolerance, although recently gaining attention, impacts an estimated 1 to 3 percent of the population, and is currently on BIO-CAT’s roadmap.

NIE: Very briefly discuss the latest and greatest innovation—in harvesting, processing, product development, delivery technology or something else.

Riera: We are very excited to offer our spore probiotic, Kaneka Probiotics Unique IS-2. The robust and stable nature of this spore makes it appropriate for many different finished formats. This allows for more creativity in developing a product, so companies can reach more consumers. Many people are experiencing “pill fatigue” and would like to take their supplements in new and improved ways. Kaneka Probiotic’s Unique IS-2 can withstand harsh manufacturing conditions and be utilized in water-based liquids, beverages, gummies, free-form powder, baked goods and more.

Sadewasser: Kemin’s ButiShield, an encapsulated source of calcium butyrate providing butyric acid, utilizes MicroPEARLS technology to deliver a low-odor encapsulate that is easier to formulate with and handle. The MicroPEARLS encapsulation technology allows for sustained and controlled release of butyric acid in the gastrointestinal tract. This proprietary spray-freezing technology helps to mask the typical odor of butyrate allowing for a low-odor source of calcium butyrate.

Bush: There are many innovations and improvements to the ways in which we currently manufacture ingredients and finished products. For instance, gummies are finally being made with less sugar. Also, brands are seeking out ingredients with minimal processing and less environmentally caustic manufacturing processes.

Artemis was one of the early suppliers of minimally processed standardized extracts with a strong sustainability story long before sustainability became what it is today. Using a completely physical membrane extraction process versus an ethanolic extraction makes our extracts clean and highly sustainable, and we use the entire berry in the process. We call it our “no material left behind” process. Waste is minimal and any spent material is repurposed for other uses. It’s a perfect sustainability story.

NIE: In a paragraph or two, what one branded ingredient do manufacturers need to be aware of and why?

Pande: LactoSpore is Sabinsa’s probiotic of strain Bacillus coagulans MTCC5856. B. coagulans changed the landscape of probiotics in dietary supplements and functional foods. One of the major advantages with this bacteria is its resilience under harsh conditions since it makes a protein sheath around itself and stays dormant to survive. This allows formulations like kombucha, gummies, candies and even coffee and baked goods to contain probiotics.

Bush: ElderCraft is definitely a brand name that formulators will want to remember. Even end users who are trying to make informed decisions in the supplement and functional food industries can seek it out by name to know the product they are buying has quality and studied functionality.

ElderCraft European Black Elderberry extract is supported by multiple clinical studies in immune support and the related category of digestive health. What also sets it apart is the controlled supply chain and gentle extraction process that retains more of the original fruit matrix while concentrating important bioactives.

Brewster: Eriomin should absolutely be on a brand manufacturer’s mind due to the four published clinical studies demonstrating its impact on prediabetes and improved gut health. This blend of citrus flavonoids is unlike other blood glucose management ingredients due to its multi-functional, integrated approach to prediabetes, which we know to impact gut health significantly. Eriomin’s triple-pronged functionality has been proven to support healthy blood glucose levels and increase insulin production by naturally boosting GLP-1, maintaining a healthy inflammation response, promoting strong antioxidant activity, and increasing the growth of beneficial bacteria associated with glycemic metabolism.

Vendrell: Recent studies have demonstrated that DAOgest plus vitamin C has the greatest histamine degrading activity compared to other DAO products on the market. Combining vitamin C with our DAO solution boosts the enzymatic activity of the DAO enzyme; increasing the histamine degrading capacity of the formulation and consequent histamine breakdown. With this in mind, bringing this combination of ingredients to market could be a game-changer for consumers with histamine intolerance.

Alimonti: Our portfolio includes a wide variety of clinically validated biotics that meet a number of highly relevant indications at this time: women’s health, infant health, mood support, weight management, immune support, oral health, skin health and more. NIE

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