Admin
Today’s ingredients pack a wallop for digestion and gut health.
The Panel:
Ramona Billingslea, Marketing Manager, Betsy’s Health Foods, Spring, TX, www.betsyhealth.com
Jennifer Brix, ND, Health Educator, Natural Factors, Monroe, WA, https://naturalfactors.com
Gene Bruno, MS, MHS, RH(AHG), Vice President of Scientific and Regulatory Affairs, NutraScience Labs (Twinlab Consolidated Corporation), Farmingdale, NY, www.nutrasciencelabs.com and www.twinlab.com
Andrea Burton, Technical Advisor, ADM Protexin, Miami, FL, www.bio-kult.com, Protexin, Somerset, England, www.protexin.com
Justin Green, PhD, Director of Scientific Affairs, Cargill Health Technologies, Ankeny, IA, https://epicorimmune.com
Vicky Mak, Technical Writer, ChildLife Nutrition, El Segundo, CA, https://childlifenutrition.com
Len Monheit, CEO, Industry Transparency Center and Executive Director of the Global Prebiotic Association, Chicago, IL, https://itcstrategy.com
Anurag Pande, PhD, Vice President Scientific Affairs, Sabinsa, East Windsor, NJ, https://sabinsa.com
Ross Pelton, Director of Science & Education, Essential Formulas, Farmers Branch, TX, https://essentialformulas.com
Jodi Schneider, National Educator, Vibrant Health, Shelton, CT, https://vibranthealth.com
With the global digestive health market estimated value at $44.4 billion in 2022 and microbiome subcategories predicted to grow at a rate of 5.8 to 10 percent by 2027 to 2029, we could say that it’s much more than a gut feeling that the overall master category is indeed packing quite the market punch.
Here to help us sort it out is a distinguished panel of dietary supplement industry experts.
VR: What is the state of the market for digestive-health supplements and digestive-health-supportive functional foods and beverages?
Pande: The digestive market has shown healthy growth in sales over the last decade, largely thanks to studies on probiotic benefits and evolving science on the microbiome. We have seen a surge in the demand for digestive health supplements since the pandemic started. The current growth rate for the digestive health market is a healthy +5 percent CAGR and is likely to stay on course in the coming future, as more and more research is looking into beneficial aspects of a healthy microbiome on the whole body.
Green: Consumer interest in digestive health is on the rise as they learn more about the gut microbiome and its role in overall health and wellness. Research from FMCG Gurus finds nearly eight in 10 consumers recognize that link, up 10 percentage points since 2018.
Digestive health is a big part of the supplement space, and a category that’s delivered steady sales growth. But consumers also recognize their food and beverage choices have a significant impact on their digestive health. Research from HealthFocus International finds improving digestion is one of the top health benefits shoppers seek in their food and beverage purchases.
Monheit: While the market for probiotics has flattened, many companies in the supplement space have taken to co-formulation with prebiotics and now postbiotics. We’ve also seen the emergence of prebiotic functional foods and beverages (including tonics), especially with emerging science and the ability through innovation to formulate at lower dosages with newer prebiotics. Many of these are targeting digestive health, although some are more broad and non-specific, targeting overall microbiome health or inferring the immune benefit.
Burton: According to Grand View Research, the global digestive health supplements market size was estimated at $8.67 billion in 2018 and is anticipated to expand at a CAGR of 8.8 percent during 2019-2025 period. According to Mordor Intelligence, the United States digestive supplements market is projected to grow at a CAGR of 7.02 percent during the period 2022-2027.
It is suspected that COVID-19 has impacted the market which has witnessed a surge in demand for products that provide digestive and immune health. The high prevalence of gastrointestinal problems, such as heartburn, constipation and diarrhea, resulted in an increasing number of consumers seeking digestive supplements regularly. The shift toward preventive digestive health management practices, amid rising health care costs and the growing burden of lifestyle diseases, is a major factor driving the digestive health supplements market.
VR: Although microbiome (microbial) health is at the center of digestion, what does the market look like for prebiotics, probiotics, synbiotics and postbiotics?
Pelton: As to the global prebiotics market, analysts predict the global market for prebiotics will experience strong growth, going from $4.5 billion to an estimated $8.8 billion by 2027 for a CAGR of 9.9 percent.
The global synbiotics market is also expected to grow. It was valued at $0.80 billion in 2022 and growing at a CAGR of 8.20 percent from 2022 to 2030. The market is expected to reach $1.50 billion by 2030.
The global postbiotics market was valued at $ 9.5 million in 2022. Rising consumer awareness of the health benefits of postbiotics will fuel strong demand for postbiotic. This segment is expected to grow at CAGR of 11.5 percent to reach $28.3 billion by 2032.
Pande: The microbiome has definitely been center-stage for the digestive health category, and around this the market of probiotic, prebiotics, synbiotics and postbiotics has developed. Today for digestive health, the probiotics and family (prebiotic, postbiotic, synbiotic) are the most sought-after ingredients. Studies have shown positive correlation of probiotics consumption on digestive health as well as immune and other health benefits.
Studies have also shown that probiotic intake has improved the microflora and related digestive health, the benefits of prebiotic in combination with probiotic are now well documented with clinical studies. One good example is Sabinsa’s LactoWise and Lacto-Cran d’Or. These combinations have a common bacterial strain, LactoSpore MTCC 5856. Both LactoCran and LactoWise are unique as the prebiotic parts were studied specifically for growth of the probiotic component; this was first custom made prebiotic combination.
Burton: According to Fortune Business Insights, the global probiotics market, specifically, was valued at $48.88 billion in 2019 and is projected to rise to $94.48 billion by 2027. In 2021 the global probiotics market was valued by Coherent Market Insights at $54.9 billion in terms of revenue, exhibiting a CAGR of 6.9 percent during the forecast period (2022 to 2030). And in 2022, Market and Markets valued the global probiotics market at $57.8 billion. The Mordor Intelligence report suggests that probiotics are the driving force within the booming digestive health supplement category, followed by digestive enzymes.
Schneider: There is increased awareness that a healthy microbiome is necessary for our physical and mental health. Probiotics and prebiotics, postbiotics and synbiotics have been receiving an overwhelming amount of attention with continued growth in the market.
Monheit: The market for traditional prebiotics like inulin and FOS has increased but has been frustrated by lack of capacity. We’ve also seen the emergence of newer prebiotics such as resistant starch, polyphenols with prebiotic activity, XOS and AXOS to name a few.
Some new activity is being driven by consumer desire for the “synbiotic concept” and always looking for novelty, a portion of the consumer base is looking for postbiotics, supported by developers who are taking advantage of the lack of formulation restrictions compared to probiotics and also the emerging science base regarding these cell materials and metabolites of probiotics.
From a future-casting perspective, this broader “a healthier microbiome means a healthier you,” is a theme we think will continue to drive innovation, product positioning and market growth for years to come.
Green: Our research suggests all these health-supportive ingredients have a positive outlook. While consumers are most familiar with pre- and probiotics, awareness and interest in postbiotics is growing rapidly. Our latest consumer research finds nearly half of all consumers are aware of postbiotics, and a similar number are open to purchasing products made with them.
VR: Two-part question: 1, is the gut-brain axis connection informing a lot of formulating today? and 2, are retailers and consumers becoming more familiar with the concept?
Billingslea: I think that people are becoming more familiar with the concept. I know that when we’re explaining this concept to customers, we’re finding more and more who are already familiar with the idea. Our Betsy’s Basics Mood Formula probiotic is exactly in line with the concept of the gut-brain connection.
I think it’s important for people to learn about the connection between the heart and the gut, as well. All of this synergy in our body just underscores the growing need for all of us, regardless of how healthy we are or are not, to support our healthiest gut!
I have a personal investment in gut health because I was diagnosed with Crohn’s disease in 2020.
Bruno: While I have seen some product formulations informed by the gut-brain axis connection, I would not say that it is informing a lot of formulations. This is definitely an area of opportunity for brand owners. It is likely that retailers and consumers are becoming somewhat more familiar with the concept. That being said, if you conduct a Google search you will see the majority of hits on the topic are peer-reviewed and technical articles, not articles from the popular press (although there are a few). This suggests to me that many retailers and consumers are still not familiar with the concept.
Schneider: Consumers are more aware of the importance of gut health on the mind and body’s well-being. Brain/mood-targeted probiotic supplements are on the rise. It has been one of the fastest-growing sectors in the market over the past few years.
Monheit: Answering the second piece first, yes, retailers are beginning to understand the concept as are consumers, and let’s face it, mental wellness is the largest umbrella concern. The science behind gut-brain is still relatively early, but the connection and theoretical mechanisms are driving positioning if not outright innovation in formulation. The brain health category is one of the more experiential, so we are seeing some ingredient additions that are seeking to leverage this axis and connection.
Pelton: Industry interest in formulating products based on the gut-brain axis to support mental health is growing. Last year the Gut-Brain Axis 2021 summit brought together leading scientists, physicians and senior leaders to explore the potential insights into the microbiota–gut–brain axis, the human microbiome market that exhibits significant potential in the near future.
An example of the interest in this segment is the joint venture between industry giant Unilever and the gut microbiome company Holobiome with goal of discovering ingredients for food and drinks that target the gut-brain axis and improve mental well-being.
As to the gut-brain axis, retailers and consumers becoming more familiar the concept and are creating a greater demand for products that help improve mental health.
Burton: While it is difficult to formulate products to support the brain directly, recent evidence clearly supports targeting the gut to benefit the brain, mental health and mood. Consumers understand that the digestive tract is very sensitive to our emotions (e.g., the feeling of butterflies when we’re feeling nervous) so they’re well aware of the link between the gut and the brain. Hopefully they are also beginning to understand that actually approximately 80-90 percent of the communication signals between the brain and gut via the vagus nerve move upwards, meaning they originate in the gut and relay messages back up to the brain, while only 10-20 percent of the messages are sent from the brain down to the gut.
VR: How important are glutamine and collagen for gut and intestinal health, respectively, and are more formulas including them?
Brix: L-glutamine and collagen play vital roles in supporting gut health. L-glutamine supplementation has been shown to support the gut lining, influence the gut microbiome and modulate gut inflammation. Research continues to unravel how collagen benefits the gut, but current studies indicate collagen has anti-inflammatory and antioxidant effects and may reduce leaky gut. Initial research also shows collagen supplementation may reduce bloating and improve bowel frequency. We should see more formulations integrating these two key nutrients for gut healing.
Monheit: Solnul recently presented results of clinical research on blood metabolite 5-Hydroxylysine and how Solnul helps reduce this marker of collagen degradation. We’re also seeing companies like U.K.-based Advance Biotics utilize collagen in their formulation—Advanced Biotics combines collagen, prebiotic (GOS) and a postbiotic. We haven’t seen collagen or glutamine reach mainstream yet though.
Burton: A 2021 report looked at the role of glutamine in supporting gut health and neuropsychiatric factors and it concluded that glutamine may offer a powerful adjunct as direct support for fundamental health maintenance, immune system function, microbiome balance, gut function and lower levels of gut inflammation as well as indirect nutritional support when addressing neuropsychiatric conditions.
However, it is important to take into account the complete medical picture of a person before recommending glutamine and anyone with a history of kidney disease, liver disease, Reye’s syndrome or cancer should not take glutamine. It should also not be used when taking certain medications such as antiseizure medications.
Bruno: Glutamine is fairly well established for its role in gut health. In gut physiology, glutamine promotes enterocyte proliferation, regulates tight junction proteins, suppresses pro-inflammatory signaling pathways, and protects cells against apoptosis and cellular stresses during normal and pathologic conditions.
Collagen supplementation also holds promise. However, research revealed that consumer awareness of collagen for digestive health is low (31.4 percent). Among subjects who completed a study using collagen for digestive health, 93 percent experienced a reduction in digestive symptoms, which included bloating.
Schneider: Glutamine is a major nutrient to maintain the intestinal barrier aiding in tight junctures. Depletion of glutamine has been shown to increase the risk of gut permeability. Glutamine may also improve digestion by strengthening the intestinal barrier; it may also reduce symptoms of IBS. Collagen can help alleviate mild digestive issues and bloating along with improving gut barrier function.
Both ingredients are beneficial to the health of the gut microbiome. It is important for formulas to look at the microbiome, as a whole, addressing the lining of the GI tract, not just probiotics and prebiotics. There are some formulas that contain all of these ingredients.
VR: What are the top 1–3 clinical science-backed ingredients to tackle heartburn and indigestion and/or promote healing? Do zinc carnosine and DGL licorice still make the list?
Pelton: DGL is very effective for many people with heartburn and GERD. For years, my No. 1 recommendation for heartburn and/or reflux is a product named Acid Block by Rx Vitamins. In addition to DGL, it also contains alginate. When these tablets are chewed and the alginate enters the stomach, it forms millions of tiny bubbles that float on the surface of the contents in the stomach. This creates a barrier that prevents stomach contents from refluxing up into the esophagus.
Pande: Heartburn, bloating, overfullness and gastric pain are symptoms caused by chronic indigestion or dyspepsia. Functional dyspepsia is referred to as non-ulcer dyspepsia. Digestive enzymes can be quite effective in managing these conditions.
One such proprietary blend of enzymes, Sabinsa’s DigeZyme was recently studied in humans for management of functional dyspepsia. Dosage of 50 mg three times a day was found to be effective in managing symptoms related to functional dyspepsia. While DGL is still used in the formulations for assisting heartburn, formulators and consumers are looking for new ingredients with scientifically backed benefits.
Bruno: A body of research certainly supports the use of zinc carnosine and DGL licorice for ulcers, but these nutraceuticals are less likely to have the same efficacy for general heartburn and indigestion.
Schneider: DGL is still a top ingredient for heartburn. Other well-studied ingredients are marshmallow root, slippery elm, chamomile and D-limonene.
Burton: A 2022 review of 16 human clinical trials into the effectiveness of nutritional ingredients on upper gastrointestinal conditions and symptoms suggests that melatonin and marine alginate appear promising for gastro-esophageal reflux disease symptoms (such as heartburn and indigestion). However, it recommends that more research and evidence for melatonin and marine alginate are needed to determine their effectiveness and the appropriate dose for each.
The report suggests that fenugreek, galactomannan, and zinc-l-carnosine also represent promising areas for further study. They also looked at aloe vera, papaya and licorice, but further investigation of each ingredient is needed to understand their specific effects in the gut.
Brix: Currently, the top science-backed ingredients to tackle heartburn and indigestion include mastic gum, zinc carnosine and ginger.
Mastic gum is known for its anti-inflammatory, antioxidant, and antimicrobial effects. The antibacterial activity of mastic gum against Helicobacter pylori (H. pylori) has been widely investigated. H. pylori has been implicated as an important factor in digestive concerns such as gastritis.
Zinc L-carnosine supports healthy inflammatory responses and helps to protect and heal the cell lining of the stomach and intestines, while ginger has a long history of relieving indigestion, heartburn and nausea.
Keep in mind that other ingredients—such as DGL, peppermint and demulcent herbs, such as marshmallow and slippery elm—[can] provide many benefits for these health concerns.
VR: What are the top one or two clinical science-backed finished products for digestive health?
Brix: The top science-backed finished products include Gastro-Assist and ReliefBiotic IB from Natural Factors. Gastro-Assist is a synergistic formula combining mastic gum, Bifidobacterium longum BB536, Saccharomyces boulardii, chamomile extract and zinc L-carnosine. Together, these key functional ingredients promote the health of the GI tract, help to encourage a healthy gut flora balance, and support the cells lining the stomach and intestines.
ReliefBiotic IB is an innovative formula featuring four probiotic strains shown to support healthy digestion and minimize occasional gastrointestinal disturbances, such as diarrhea, bloating and gas. This probiotic features Lactobacillus rhamnosus (R0011) and Lactobacillus helvetica (R0052), a probiotic combination backed by over 20 years of research and 22 clinical studies. It has been shown effective in supporting healthy intestinal flora balance after antibiotic use in children and adults. In addition, Bacillus subtilis (R0179) and Enterococcus faecium (R0026) provide further gastrointestinal support.
Monheit: On the finished product side, Olipop and Supergut both have substantial science and formulation expertise behind them. Both have proprietary science on the brand itself, innovation, flavor, convenience.
Pelton: Dr. Ohhira’s Probiotics is one of the top science-based products for digestive health. Common symptoms related to digestive health problems are gas, bloating, diarrhea, constipation, inflammation and pain. These symptoms are often caused by microbial imbalance in the GI tract, also known as dysbiosis.
A major paradigm shift is happening in microbiome science with the emerging understanding of the key role that postbiotic metabolites play in regulating the health of the microbiome ecosystem. Dr. Ohhira’s Probiotics are produced in a multi-year fermentation system that results in the production of over 500 postbiotic metabolites. Over 22,000 postbiotic metabolites have been identified thus far. Some of the key functions of postbiotic metabolites include anti-inflammatory activity, create a slightly acidic pH in the microbiome ecosystem, which inhibits the growth of pathogens and promotes the growth of probiotic bacteria, they send signals to the brain, which influence mood, appetite and satiety, and much more.
Direct delivery of postbiotic metabolites is a much faster, more effective way to reduce the symptoms of dysbiosis and improve overall digestive health compared to just administering probiotic bacteria. In order to be effective, probiotic bacteria must make postbiotic metabolites.
Pande: At Sabinsa, digestive health is one of the top areas of research interest. Digezyme, LactoSpore, LactoWise, LactoCran, Saberry and DGL are a few of Sabinsa’s ingredients backed by science and clinical studies. LactoSpore and DigeZyme definitely would rank as the top two products in this segment.
LactoSpore is a probiotic containing Bacillus coagulans MTCC 5856 strain bacteria, which is well researched and clinically studied for gut health. In the clinical studies, LactoSpore has also shown its beneficial effect on the gut brain axis, which is an area of great interest. One of the reasons why LactoSpore has been considered as a probiotic of choice is its low dosage is owing to its better viability than most of the other probiotic bacterial strains.
The bacillus strain in LactoSpore is a spore-forming strain, that protects itself from the low pH acid in gut during the gut transit. It also is protected from the manufacturing stress while making tablets, gummies or other formulations where it is exposed to both low pH and high temperature. Clinical studies on LactoSpore show that this strain of bacteria can support healthy microflora and support healthy digestive health overall. LactoSpore is also a GRAS (generally recognized as safe) ingredient, and couples with its stability under extreme conditions makes it a popular ingredient in functional foods and beverages.
Burton: A search for recent research shows that there have been 16,284 published studies on probiotics since the beginning of 2020. Where many probiotic companies buy in their bacteria strains, Bio-Kult Original is formulated with its own PXN strains, meaning the clinical research is based on the finished product opposed to the strains alone. Bio-Kult Original has been used in recent published studies such as the largest clinical study in IBS-D, migraine and most recently in low mood.
Schneider: I believe it is very important to look at the whole microbiological system. This means not only taking only probiotics, prebiotics, and postbiotics but also providing nutrients that support a healthy gastrointestinal lining and incorporating food-derived antioxidant compounds to aid in protection from intestinal oxidative stress and alleviate inflammation. Ingredients such as curcumin and boswellia, which are clinically backed, provide this protection.
Digestive Vibrance from Vibrant Health provides these ingredients and more making it a comprehensive formula supporting the entire microbiological system.
Mak: Depending on their children’s needs, parents may select the following two products offered by ChildLife Essentials to support their children’s digestive health. ChildLife Essentials has formulated both ChildBiotics Probiotics with Colostrum and LiveBiotics Immune & Digestive Support for healthy growth and development in children.
Both products consist of bioactive ingredients, such as probiotic strains Lactobacillus acidophilus DDS-1 and Bifidobacterium lactis UABla-12, that exhibit gut-supporting abilities as well as immunomodulatory effects. DDS-1 and UABla-12 have been clinically researched for their physiological interactions with the gut-immune axis. DDS-1, alone or with UABla-12, can modulate gut microbiota by increasing the relative abundance of beneficial bacteria and reducing levels of opportunistic bacteria. In addition to improving bowel habits, stomach discomfort, and quality of life, this combination of DDS-1 and UABla-12 can help promote healthy immune responses, reducing inflammation induced by environmental substances and supporting pediatric development.
ChildLife Essentials ensures that these pediatric dietary supplements contain only the highest-quality ingredients while committing to the top standards for an all-natural, clean and sustainably sourced brand for informed consumers.
Both ChildBiotics Probiotics with Colostrum and LiveBiotics Immune and Digestive Support are free of artificial colors, flavors and sweeteners and are formulated with delicious, kid-approved, natural fruit flavors. ChildBiotics Probiotics with Colostrum is made in a ready-to-mix powder form to add in food and drinks for infants and children to easily consume; this product blends the natural sweetness of fresh colostrum with a natural tropical orange flavor while providing a unique combination of health-promoting probiotics and first-milking colostrum in a single serving. LiveBiotics Immune & Digestive Support is free of the top nine allergens (wheat, fish, milk, peanuts, soy, tree nuts, shellfish, eggs and sesame), preservative-free, non-GMO, vegan and sugar-free; this product is naturally sweetened with a delicious natural berry flavor and formulated specifically for children beginning at age 1 year through their teen years. Both products are gluten-free and contain no egg, soy and wheat.
Billingslea: Our most popular gut health products are our Betsy’s Basics (store brand) probiotics. We have a variety of them to meet specific needs. Our 35 Billion and Women’s 50 Billion are our two most popular.
For digestion, our Betsy’s Basics Superzymes is the most popular enzyme. We also have our Betsy’s Basics Aloe Vera Plus: 1 cap equals 2 oz. of Fresh Organic Aloe, and the Plus includes marshmallow root and slippery elm bark. Betsy’s Basics Triphala is another must for digestion support. Our Betsy’s Basics Ginger and DGL products are also an important part of our gut health and digestion category.
Natural Factors Gastro-Assist is another popular product in this category.
VR: Prebiotics—carbohydrates, resistant starches, pectins, etc.—have become very popular. Please cite one or two of your favorite science-validated prebiotic ingredients or formulas.
Schneider: Pomegranate is a great prebiotic because it stimulates the growth of gut bacteria and is protective against degenerative diseases. Larch arabinogalactans are a great source of dietary fiber that stimulates the growth of beneficial bacteria along with support for digestive health.
Bruno: One downside to prebiotics is that several grams (5 or more) are typically required in order to provide clinical benefit. There is, however, one exception to this: PreticX branded xylooligosaccharide (XOS) from AIDP, which have been shown to provide prebiotic benefits with just a dose of about 1 g. This was demonstrated in a double-blind, randomized, placebo-controlled study in which XOS was tolerated without significant gastrointestinal side effects, and bifidobacterium counts increased significantly.
Burton: Beneficial lactobacilli and bifidobacteria are more efficient at fermenting these prebiotic foods than pathogenic strains (meaning they stimulate their growth) and produce a lot less (if any) gas during fermentation.
A 2022 study concluded that FOS supplementation could increase the number of colonic Bifidobacterium spp. while higher dose (7.5–15 g/d) and longer duration (>4 weeks) showed more distinct effects and was well tolerated.
However, initially, until levels of beneficial species are increased, prebiotics can cause bloating in some people so it’s best to introduce prebiotic foods or a prebiotic supplement gradually. Monheit: This category is more than just probiotics—prebiotics have gained traction because they meet the need to nurture and support the microbiome full stop. Also, new developments mean lower dosages, ease and convenience. Resistant starch like Solnul, GOS (Clasado’s Bimuno), Anagenix (Livaux) are some with strong clinical substantiation, and across the board the science is increasing in this category.
Pelton: Balance and diversity are critical for microbiome health. Taking large amounts of a prebiotic may be helpful. However, ingesting a large dose of a prebiotic actually works against balance and diversity. People should strive to eat small amounts of many different types of prebiotic foods daily. This promotes the growth of a diversity of probiotic bacteria, which in turn, will produce a diversity of health-regulating postbiotic metabolites.
VR: We know that probiotics are big—especially considering the gut-brain axis, and now also the gut-bone axis—briefly cite one or two of your favorite science-validated probiotic ingredients or formulas.
Burton: The probiotic supplement Bio-Kult Original was recently used in a study at the University of Oxford on low mood and emotional salience. This was a double-blind placebo-controlled trial in 70 people who were experiencing low mood, half were given a placebo and the other half were given the Bio-Kult probiotic blend. They were taking two capsules twice a day for a month and the participants reported their mood via a Patient Health Questionnaire for Depression. The result from the documentary showed a 20 percent improvement in mood for those in the placebo group versus a 50 percent improvement in mood in those taking Bio-Kult. The supplement group also reported a 50 percent improvement in their concentration.
In terms of the gut-bone axis, a 2020 review highlighted how modulation of the gut microbiota is an attractive therapeutic intervention to counteract bone loss. The review looked at iron, selenium, zinc, calcium and vitamin D along with prebiotics, probiotics, postbiotics and synbiotics and suggested these interventions should be explored further as useful adjuvant treatments for osteoporosis.
Pelton: I would call out Dr. Ohhira’s Probiotics, which contains probiotics, prebiotics, and most importantly, over 500 postbiotic metabolites.
Pande: LactoSpore that has undergone clinical studies for management of gut health with specific focus toward the gut brain axis-related health conditions. In two studies which included subjects with irritable bowel syndrome, LactoSpore was supplemented at 2 billion spores/day. Clinical results showed not only improvement in gut health—such as intestinal pain, and bloating, which are common occurrences in such patients—but also improvement in major depressive disorder, or in other words positive mood benefits. IBS is a gut-brain-axis-related health condition and improvement in the clinical parameters showed direct benefit of LactoSpore on gut-brain axis. All the studies on LactoSpore were carried out at 2 billion spores/day.
Brix: The gut is connected to everything, and new research is revealing that many axis exist throughout the body. In terms of the gut-brain axis, certain probiotic formulas have been shown to help moderate general feelings of anxiousness, promote a healthy mood balance and relieve stress-related gastrointestinal complications.
One double-blind, placebo-controlled, randomized, parallel group study of healthy adults who took 3 billion colony forming units of Bifidobacterium longum subsp. longum (R0175) and Lactobacillus helveticus (R0052), showed decreases in scores on two psychological distress tests. Average urinary levels of the stress hormone cortisol also decreased, and a follow-up study found that those with the lowest baseline cortisol levels had the most significant improvements in scores related to mood and feelings of anxiousness.
Mak: Lactobacillus rhamnosus LGG and Bifidobacterium animalis subsp. lactis BB-12 are well-known probiotic strains that have been clinically studied in infants and children. Administration of LGG in children has demonstrated fewer incidences, shorter episodes of loose and watery stools, and normal bowel habits. In relation to immune challenges related to respiratory health, LGG has been associated with fewer respiratory challenges and significantly fewer days with signs of respiratory discomfort. BB-12 was shown to be associated with softer and more frequent bowel movements, shorter and fewer episodes of loose stools, and overall regularity. In one clinical study, BB-12 supplementation among healthy, full-term infants resulted in better gut immune response. BB-12 may also reduce the duration of crying in fussy infants and thus significantly improve the quality of life for parents and caregivers. Based on these findings, ChildLife Essentials has formulated InfantBiotics Probiotic Drops with both proprietary probiotics LGG and BB-12 to reduce stomach discomfort and duration of loose stools in infants and children.
VR: Postbiotics must be part of the conversation, too, especially considering the newer entries geared to support digestive, immune, and skin health; briefly cite one or two of your favorite science-validated postbiotic ingredients or formulas.
Green: Each postbiotic is unique, based on the microorganism, the fermentation medium and method used, the post-fermentation process, and its ability to confer a health benefit on the host. Cargill’s postbiotic, EpiCor, is backed by over 75 years of fermentation expertise. It is made using baker’s yeast (Saccharomyces cerevisiae) that goes through a natural fermentation process, which creates a unique fingerprint of metabolites. After the fermentation process, it is gently dried using a proprietary heating process that kills off the yeast, while still preserving all the metabolites and functional compounds. Over a dozen published studies, including multiple human clinical trials, show that EpiCor postbiotic supports the gut microbiome, as well as immune health and nasal comfort.
Human clinical research has shown that EpiCor postbiotic helps positively modulate beneficial bacterial populations and, in model studies, may support short chain fatty acid production, effects that highlight how the ingredient can play an important part supporting the gut microbiome.
EpiCor postbiotic was first established in the supplement space, but our application scientists have found it’s a good fit for functional foods and beverages, too. Its recommended dose is just 500 mg per day, making it easy to formulate into a wide array of functional products, including gummies, nutrition bars and beverage shots.
Burton: A favorite postbiotic is heat-treated Bifidobacterium longum ES1 bacterial strain which has been shown to have the capacity to protect against oxidative damage, as well as inhibit bacterial colonization, by activating biological pathways related to our innate immune function.
Due to its anti-inflammatory/antioxidant profile, this strain has also been used in probiotic formulations shown to improve symptomatology derived from atopic dermatitis, psoriasis, and asthenozoospermia—conditions which are related to damaged intestinal integrity.
Pelton: Butyrate is a critically important postbiotic metabolite. It has anti-inflammatory activity, it is the primary agent that supplies energy to colonic epithelial cells, and it enhances intestinal barrier function and mucosal immunity. Phenyllactic acid is a postbiotic metabolite that is produced by Enterococcus faecalis TH10. It has been shown to exert antifungal and antibacterial activity, especially against MRSA.
Monheit: We’re fans of LBiome from Stratum and Immuse from Kyowa Hakko.
Pande: Recently Sabinsa launched an innovative postbiotic preparation from its patented probiotic strain Bacillus coagulans MTCC 5856. This postbiotic, ImmunoSpore, has been studied for its immune boosting activity as well as anti-inflammatory activity. It was found that ImmunoSpore can upregulate the expression of inducible form of nitric oxide synthase (iNOS) that can improve the immune defense against pathogens. ImmunoSpore has been standardized to contains 15 billion inactivated spores.
Bruno: I like a postbiotic commercially known as Immuno-LP20 (by Mitsubishi). Research shows supplementation with 50 mg augments acquired immunity, especially Th1-related immune functions in healthy subjects, thereby improving the health-related QOL. Likewise, 50 mg of Immuno-LP20 was found to stimulate type I interferon (IFN) in humans given an influenza vaccine. This same dose was found to decrease upper respiratory tract infection incidence in healthy subjects, likely through augmentation of immunity. In addition, daily intake of Immuno-LP20 improved inflammation and lipid metabolism (including decreases of total cholesterol, and LDL cholesterol) in subjects at risk of inflammation.
VR: We know that synbiotics typically combine prebiotics and postbiotics, but there are also emerging finished products that combine prebiotics, probiotics and postbiotics, in some cases along with botanical complements. Please cite your one or two science-backed favorites.
Pande: Two of the synbiotic combinations that we manufacture as customized products are LactoWise and LactoCran. With these products we change the way synbiotics are formulated. The selection of prebiotic for any probiotic is an important process, as each bacterium may have different nutritional needs for growth. The prebiotic part of these formulations was screened for stability and their prebiotic activity against standard prebiotic fibers to [ensure a] high-performing synbiotic combination. Lactowise and LactoCran both show high stability and are sought after as synbiotic combinations containing clinically studied probiotic.
Pelton: Dr. Ohhira’s Probiotics, which contains probiotics, prebiotics and postbiotic metabolites. Interestingly enough, it is not really “new,” but has been on the market in the U.S. for over 23 years! The research and development of the product by Dr. Ohhira started over 40 years ago using traditional Japanese fermentation techniques in strict accordance with most advanced pharmaceutical standards and has led to the product being one of the most trusted and proven formulas throughout the world. Dr. Ohhira’s Probiotics has been studied extensively over that time period with published results in numerous professional journals (most often under the Japanese name for the product OM-X).
Monheit: Ritual Synbiotic+ and Seed DS-01 Daily Synbiotic are formulations with prebiotics, probiotics and postbiotics that have solid science behind them.
VR: What ingredients (or product types) were not mentioned but you would like to shine a spotlight on?
Burton: Beta-glucans are a group of fibers that are suggested to exhibit a wide range of potential health benefits; including immune support, weight management, cardiovascular support, mood support and overall improved wellbeing. Beta-glucans are fermented by intestinal bacteria, potentially altering the composition of the gut microbiota, favoring species that exhibit beneficial compounds; with immunomodulatory, anti-tumor, anti-microbial and anti-oxidant properties.
Beta-glucans may also be helpful in managing inflammation as described in a 2020 randomized controlled trial in 31 healthy adult males and females. Individuals took 250 mg of yeast beta-glucans or placebo for 13 days while taking part in a prolonged bout of heated treadmill exercise. Concentrations of pro-inflammatory cells in the intervention group were significantly lower than the placebo group.
Pelton: Glutathione is one of the most important multi-tasking compounds in biology. It is the most prevalent antioxidant in humans, it plays key roles in detoxification, it is critical for immune function and it expresses powerful anti-viral activity.
A unique strain of probiotic bacteria named Lactobacillus fermentum ME-3 synthesizes substantial amounts of glutathione. Thus, glutathione is a postbiotic metabolite produced by ME-3. Human clinical trials reveal that people taking ME-3 gain numerous important health benefits including reduced levels of oxidized LDL-cholesterol, lower levels of free radical production, a 26 percent increase in total antioxidant activity, and 49 percent increase in the ratio between reduced to oxidized glutathione. Animal studies report a reduction in glycation and improved insulin sensitivity.
Brix: There are two areas that I think deserve attention. The first we didn’t touch on is supplements for small intestinal bacterial overgrowth (SIBO). With SIBO, no matter how much fiber, prebiotics, probiotics, or postbiotics you use, it typically won’t be eradicated until an antibacterial protocol is followed. In fact, certain probiotics and prebiotics can really exacerbate symptoms of bloating and bowel changes, so herbal extracts and oils from herbs such as oregano, peppermint, barberry and garlic, as well as specific enzymes, are used to help eliminate the cause of this very common condition.
The second is bacteriophages. Bacteriophages are viruses and are the most abundant member of the gut virobiota. Evidence is mounting that they may provide protective immunomodulating and anti-inflammatory activity. Although we are a way off from supplementing with viral material, understanding the role of the virobiome is exciting and unearthing further intricacies of gut health.
VR: Where do you see the digestive health, microbial health or the combined categories evolving?
Green: Given how foundational digestive and microbial health is to overall well-being, we expect demand for products that support gut health to continue their upward trajectory. In particular, we see plenty of upside for postbiotics. Our proprietary research finds half of U.S. shoppers are familiar with postbiotics—a great start for this relative newcomer to the consumer space. As we continue to invest to build consumer awareness for the category and our ingredient, EpiCor postbiotic, we expect this number will continue to grow.
Pande: The digestive health category is definitely going to stay strong, it is quite possible that microbiome related category will diversify from digestive health to immune, sports, cognitive health, as studies on microbiome are expanding understanding of the effect of the gut microbes on all these areas apart from digestive health.
Pelton: I believe that interest in digestive health and microbial health will grow substantially in the coming years as people learn more about the critical role the gut microbiome plays in regulating many aspects of health. I have written an article titled “The Microbiome Theory of Aging,” which has been accepted for publication in a medical journal. The article explains why microbial imbalance and microbiome dysfunction cause intestinal permeability (leaky gut), which results in many health problems and the acceleration of biological aging.
Burton: The next few years will see interesting and exciting developments in the microbial health market with companies investigating novel ways of providing probiotics to consumers. A study in September 2022 looked at whether it could be beneficial to intervene in environments within which children live to ensure exposure to more varied microbes at a young age. The study investigated whether it was possible to enhance gut microbial diversity and richness in children through environmental interventions by looking at the environments of day care and nursery facilities as a source of microbial exposures at this crucial time of life.
The study was the first of its kind—it was a placebo-controlled, double-blind study on the effect of environmental exposures on gut microbiota diversity and immune parameters in young children. Playground sandboxes at day care centers in Finland were used as sources of environmental microbial exposure with some sandboxes being placebos and some having a microbial powder added to them. Researchers measured the composition of gut and skin microbiota, as well as blood immune markers. Altogether, 26 children ages 3–5 participated in supervised play for 20 minutes in the morning and afternoon for two weeks.
The results showed that the microbially enriched sandboxes enhanced both the bacterial richness and diversity of the children’s skin bacterial community and this enhancement was not seen in the placebo group children. The authors also found that the daily exposure to higher microbial biodiversity resulted in positive differences in immune response. Therefore, the researchers concluded that environmental microbiota may contribute to child health, and that adding microbiological diversity to everyday living environments may support immunoregulation.
This poses an exciting new possibility. Will we start to see environmental probiotics (such as probiotic toys, bedding or playgrounds) being developed in the future?
VR: Is there anything else you would like to add?
Pelton: Postbiotic metabolites are the new frontier in microbiome science. For decades, companies have been creating and marketing products with one or multiple stains of probiotic bacteria. However, a substantial shift is beginning to take place. The food, cosmetic and natural products industry are committing more money to develop products based on postbiotic metabolites. In general, postbiotics are easier to transport than probiotic bacteria. In addition to being are more stable during transportation, postbiotics have a longer shelf life than probiotics. Since postbiotics do not contain live organisms, they pose less health risks than probiotics.
It often takes a long time for new scientific ideas to become accepted. For example, it took decades for Newton’s laws of physics and Einstein’s Theory of Relativity to be accepted. The postbiotic revolution is underway. Postbiotic metabolites regulate the microbiome ecosystem. Multiple factors can cause microbial imbalance in the GI tract (antibiotics, poor diets, stress), which causes intestinal permeability, many health problems and the acceleration of biological aging.
Dr. Ohhira’s Probiotics, with over 500 postbiotic metabolites, is one of the best products to help create and maintain a healthy microbiome. VR
Extra! Extra!
Today’s ingredients pack a wallop for digestion and gut health.
The Panel:
With the global digestive health market estimated value at $44.4 billion in 2022 and microbiome subcategories predicted to grow at a rate of 5.8 to 10 percent by 2027 to 2029, we could say that it’s much more than a gut feeling that the overall master category is indeed packing quite the market punch.
Here to help us sort it out is a distinguished panel of dietary supplement industry experts.
VR: What is the state of the market for digestive-health supplements and digestive-health-supportive functional foods and beverages?
Pande: The digestive market has shown healthy growth in sales over the last decade, largely thanks to studies on probiotic benefits and evolving science on the microbiome. We have seen a surge in the demand for digestive health supplements since the pandemic started. The current growth rate for the digestive health market is a healthy +5 percent CAGR and is likely to stay on course in the coming future, as more and more research is looking into beneficial aspects of a healthy microbiome on the whole body.
Green: Consumer interest in digestive health is on the rise as they learn more about the gut microbiome and its role in overall health and wellness. Research from FMCG Gurus finds nearly eight in 10 consumers recognize that link, up 10 percentage points since 2018.
Digestive health is a big part of the supplement space, and a category that’s delivered steady sales growth. But consumers also recognize their food and beverage choices have a significant impact on their digestive health. Research from HealthFocus International finds improving digestion is one of the top health benefits shoppers seek in their food and beverage purchases.
Monheit: While the market for probiotics has flattened, many companies in the supplement space have taken to co-formulation with prebiotics and now postbiotics. We’ve also seen the emergence of prebiotic functional foods and beverages (including tonics), especially with emerging science and the ability through innovation to formulate at lower dosages with newer prebiotics. Many of these are targeting digestive health, although some are more broad and non-specific, targeting overall microbiome health or inferring the immune benefit.
Burton: According to Grand View Research, the global digestive health supplements market size was estimated at $8.67 billion in 2018 and is anticipated to expand at a CAGR of 8.8 percent during 2019-2025 period. According to Mordor Intelligence, the United States digestive supplements market is projected to grow at a CAGR of 7.02 percent during the period 2022-2027.
It is suspected that COVID-19 has impacted the market which has witnessed a surge in demand for products that provide digestive and immune health. The high prevalence of gastrointestinal problems, such as heartburn, constipation and diarrhea, resulted in an increasing number of consumers seeking digestive supplements regularly. The shift toward preventive digestive health management practices, amid rising health care costs and the growing burden of lifestyle diseases, is a major factor driving the digestive health supplements market.
VR: Although microbiome (microbial) health is at the center of digestion, what does the market look like for prebiotics, probiotics, synbiotics and postbiotics?
Pelton: As to the global prebiotics market, analysts predict the global market for prebiotics will experience strong growth, going from $4.5 billion to an estimated $8.8 billion by 2027 for a CAGR of 9.9 percent.
The global synbiotics market is also expected to grow. It was valued at $0.80 billion in 2022 and growing at a CAGR of 8.20 percent from 2022 to 2030. The market is expected to reach $1.50 billion by 2030.
The global postbiotics market was valued at $ 9.5 million in 2022. Rising consumer awareness of the health benefits of postbiotics will fuel strong demand for postbiotic. This segment is expected to grow at CAGR of 11.5 percent to reach $28.3 billion by 2032.
Pande: The microbiome has definitely been center-stage for the digestive health category, and around this the market of probiotic, prebiotics, synbiotics and postbiotics has developed. Today for digestive health, the probiotics and family (prebiotic, postbiotic, synbiotic) are the most sought-after ingredients. Studies have shown positive correlation of probiotics consumption on digestive health as well as immune and other health benefits.
Studies have also shown that probiotic intake has improved the microflora and related digestive health, the benefits of prebiotic in combination with probiotic are now well documented with clinical studies. One good example is Sabinsa’s LactoWise and Lacto-Cran d’Or. These combinations have a common bacterial strain, LactoSpore MTCC 5856. Both LactoCran and LactoWise are unique as the prebiotic parts were studied specifically for growth of the probiotic component; this was first custom made prebiotic combination.
Burton: According to Fortune Business Insights, the global probiotics market, specifically, was valued at $48.88 billion in 2019 and is projected to rise to $94.48 billion by 2027. In 2021 the global probiotics market was valued by Coherent Market Insights at $54.9 billion in terms of revenue, exhibiting a CAGR of 6.9 percent during the forecast period (2022 to 2030). And in 2022, Market and Markets valued the global probiotics market at $57.8 billion. The Mordor Intelligence report suggests that probiotics are the driving force within the booming digestive health supplement category, followed by digestive enzymes.
Schneider: There is increased awareness that a healthy microbiome is necessary for our physical and mental health. Probiotics and prebiotics, postbiotics and synbiotics have been receiving an overwhelming amount of attention with continued growth in the market.
Monheit: The market for traditional prebiotics like inulin and FOS has increased but has been frustrated by lack of capacity. We’ve also seen the emergence of newer prebiotics such as resistant starch, polyphenols with prebiotic activity, XOS and AXOS to name a few.
Some new activity is being driven by consumer desire for the “synbiotic concept” and always looking for novelty, a portion of the consumer base is looking for postbiotics, supported by developers who are taking advantage of the lack of formulation restrictions compared to probiotics and also the emerging science base regarding these cell materials and metabolites of probiotics.
From a future-casting perspective, this broader “a healthier microbiome means a healthier you,” is a theme we think will continue to drive innovation, product positioning and market growth for years to come.
Green: Our research suggests all these health-supportive ingredients have a positive outlook. While consumers are most familiar with pre- and probiotics, awareness and interest in postbiotics is growing rapidly. Our latest consumer research finds nearly half of all consumers are aware of postbiotics, and a similar number are open to purchasing products made with them.
VR: Two-part question: 1, is the gut-brain axis connection informing a lot of formulating today? and 2, are retailers and consumers becoming more familiar with the concept?
Billingslea: I think that people are becoming more familiar with the concept. I know that when we’re explaining this concept to customers, we’re finding more and more who are already familiar with the idea. Our Betsy’s Basics Mood Formula probiotic is exactly in line with the concept of the gut-brain connection.
I think it’s important for people to learn about the connection between the heart and the gut, as well. All of this synergy in our body just underscores the growing need for all of us, regardless of how healthy we are or are not, to support our healthiest gut!
I have a personal investment in gut health because I was diagnosed with Crohn’s disease in 2020.
Bruno: While I have seen some product formulations informed by the gut-brain axis connection, I would not say that it is informing a lot of formulations. This is definitely an area of opportunity for brand owners. It is likely that retailers and consumers are becoming somewhat more familiar with the concept. That being said, if you conduct a Google search you will see the majority of hits on the topic are peer-reviewed and technical articles, not articles from the popular press (although there are a few). This suggests to me that many retailers and consumers are still not familiar with the concept.
Schneider: Consumers are more aware of the importance of gut health on the mind and body’s well-being. Brain/mood-targeted probiotic supplements are on the rise. It has been one of the fastest-growing sectors in the market over the past few years.
Monheit: Answering the second piece first, yes, retailers are beginning to understand the concept as are consumers, and let’s face it, mental wellness is the largest umbrella concern. The science behind gut-brain is still relatively early, but the connection and theoretical mechanisms are driving positioning if not outright innovation in formulation. The brain health category is one of the more experiential, so we are seeing some ingredient additions that are seeking to leverage this axis and connection.
Pelton: Industry interest in formulating products based on the gut-brain axis to support mental health is growing. Last year the Gut-Brain Axis 2021 summit brought together leading scientists, physicians and senior leaders to explore the potential insights into the microbiota–gut–brain axis, the human microbiome market that exhibits significant potential in the near future.
An example of the interest in this segment is the joint venture between industry giant Unilever and the gut microbiome company Holobiome with goal of discovering ingredients for food and drinks that target the gut-brain axis and improve mental well-being.
As to the gut-brain axis, retailers and consumers becoming more familiar the concept and are creating a greater demand for products that help improve mental health.
Burton: While it is difficult to formulate products to support the brain directly, recent evidence clearly supports targeting the gut to benefit the brain, mental health and mood. Consumers understand that the digestive tract is very sensitive to our emotions (e.g., the feeling of butterflies when we’re feeling nervous) so they’re well aware of the link between the gut and the brain. Hopefully they are also beginning to understand that actually approximately 80-90 percent of the communication signals between the brain and gut via the vagus nerve move upwards, meaning they originate in the gut and relay messages back up to the brain, while only 10-20 percent of the messages are sent from the brain down to the gut.
VR: How important are glutamine and collagen for gut and intestinal health, respectively, and are more formulas including them?
Brix: L-glutamine and collagen play vital roles in supporting gut health. L-glutamine supplementation has been shown to support the gut lining, influence the gut microbiome and modulate gut inflammation. Research continues to unravel how collagen benefits the gut, but current studies indicate collagen has anti-inflammatory and antioxidant effects and may reduce leaky gut. Initial research also shows collagen supplementation may reduce bloating and improve bowel frequency. We should see more formulations integrating these two key nutrients for gut healing.
Monheit: Solnul recently presented results of clinical research on blood metabolite 5-Hydroxylysine and how Solnul helps reduce this marker of collagen degradation. We’re also seeing companies like U.K.-based Advance Biotics utilize collagen in their formulation—Advanced Biotics combines collagen, prebiotic (GOS) and a postbiotic. We haven’t seen collagen or glutamine reach mainstream yet though.
Burton: A 2021 report looked at the role of glutamine in supporting gut health and neuropsychiatric factors and it concluded that glutamine may offer a powerful adjunct as direct support for fundamental health maintenance, immune system function, microbiome balance, gut function and lower levels of gut inflammation as well as indirect nutritional support when addressing neuropsychiatric conditions.
However, it is important to take into account the complete medical picture of a person before recommending glutamine and anyone with a history of kidney disease, liver disease, Reye’s syndrome or cancer should not take glutamine. It should also not be used when taking certain medications such as antiseizure medications.
Bruno: Glutamine is fairly well established for its role in gut health. In gut physiology, glutamine promotes enterocyte proliferation, regulates tight junction proteins, suppresses pro-inflammatory signaling pathways, and protects cells against apoptosis and cellular stresses during normal and pathologic conditions.
Collagen supplementation also holds promise. However, research revealed that consumer awareness of collagen for digestive health is low (31.4 percent). Among subjects who completed a study using collagen for digestive health, 93 percent experienced a reduction in digestive symptoms, which included bloating.
Schneider: Glutamine is a major nutrient to maintain the intestinal barrier aiding in tight junctures. Depletion of glutamine has been shown to increase the risk of gut permeability. Glutamine may also improve digestion by strengthening the intestinal barrier; it may also reduce symptoms of IBS. Collagen can help alleviate mild digestive issues and bloating along with improving gut barrier function.
Both ingredients are beneficial to the health of the gut microbiome. It is important for formulas to look at the microbiome, as a whole, addressing the lining of the GI tract, not just probiotics and prebiotics. There are some formulas that contain all of these ingredients.
VR: What are the top 1–3 clinical science-backed ingredients to tackle heartburn and indigestion and/or promote healing? Do zinc carnosine and DGL licorice still make the list?
Pelton: DGL is very effective for many people with heartburn and GERD. For years, my No. 1 recommendation for heartburn and/or reflux is a product named Acid Block by Rx Vitamins. In addition to DGL, it also contains alginate. When these tablets are chewed and the alginate enters the stomach, it forms millions of tiny bubbles that float on the surface of the contents in the stomach. This creates a barrier that prevents stomach contents from refluxing up into the esophagus.
Pande: Heartburn, bloating, overfullness and gastric pain are symptoms caused by chronic indigestion or dyspepsia. Functional dyspepsia is referred to as non-ulcer dyspepsia. Digestive enzymes can be quite effective in managing these conditions.
One such proprietary blend of enzymes, Sabinsa’s DigeZyme was recently studied in humans for management of functional dyspepsia. Dosage of 50 mg three times a day was found to be effective in managing symptoms related to functional dyspepsia. While DGL is still used in the formulations for assisting heartburn, formulators and consumers are looking for new ingredients with scientifically backed benefits.
Bruno: A body of research certainly supports the use of zinc carnosine and DGL licorice for ulcers, but these nutraceuticals are less likely to have the same efficacy for general heartburn and indigestion.
Schneider: DGL is still a top ingredient for heartburn. Other well-studied ingredients are marshmallow root, slippery elm, chamomile and D-limonene.
Burton: A 2022 review of 16 human clinical trials into the effectiveness of nutritional ingredients on upper gastrointestinal conditions and symptoms suggests that melatonin and marine alginate appear promising for gastro-esophageal reflux disease symptoms (such as heartburn and indigestion). However, it recommends that more research and evidence for melatonin and marine alginate are needed to determine their effectiveness and the appropriate dose for each.
The report suggests that fenugreek, galactomannan, and zinc-l-carnosine also represent promising areas for further study. They also looked at aloe vera, papaya and licorice, but further investigation of each ingredient is needed to understand their specific effects in the gut.
Brix: Currently, the top science-backed ingredients to tackle heartburn and indigestion include mastic gum, zinc carnosine and ginger.
Mastic gum is known for its anti-inflammatory, antioxidant, and antimicrobial effects. The antibacterial activity of mastic gum against Helicobacter pylori (H. pylori) has been widely investigated. H. pylori has been implicated as an important factor in digestive concerns such as gastritis.
Zinc L-carnosine supports healthy inflammatory responses and helps to protect and heal the cell lining of the stomach and intestines, while ginger has a long history of relieving indigestion, heartburn and nausea.
Keep in mind that other ingredients—such as DGL, peppermint and demulcent herbs, such as marshmallow and slippery elm—[can] provide many benefits for these health concerns.
VR: What are the top one or two clinical science-backed finished products for digestive health?
Brix: The top science-backed finished products include Gastro-Assist and ReliefBiotic IB from Natural Factors. Gastro-Assist is a synergistic formula combining mastic gum, Bifidobacterium longum BB536, Saccharomyces boulardii, chamomile extract and zinc L-carnosine. Together, these key functional ingredients promote the health of the GI tract, help to encourage a healthy gut flora balance, and support the cells lining the stomach and intestines.
ReliefBiotic IB is an innovative formula featuring four probiotic strains shown to support healthy digestion and minimize occasional gastrointestinal disturbances, such as diarrhea, bloating and gas. This probiotic features Lactobacillus rhamnosus (R0011) and Lactobacillus helvetica (R0052), a probiotic combination backed by over 20 years of research and 22 clinical studies. It has been shown effective in supporting healthy intestinal flora balance after antibiotic use in children and adults. In addition, Bacillus subtilis (R0179) and Enterococcus faecium (R0026) provide further gastrointestinal support.
Monheit: On the finished product side, Olipop and Supergut both have substantial science and formulation expertise behind them. Both have proprietary science on the brand itself, innovation, flavor, convenience.
Pelton: Dr. Ohhira’s Probiotics is one of the top science-based products for digestive health. Common symptoms related to digestive health problems are gas, bloating, diarrhea, constipation, inflammation and pain. These symptoms are often caused by microbial imbalance in the GI tract, also known as dysbiosis.
A major paradigm shift is happening in microbiome science with the emerging understanding of the key role that postbiotic metabolites play in regulating the health of the microbiome ecosystem. Dr. Ohhira’s Probiotics are produced in a multi-year fermentation system that results in the production of over 500 postbiotic metabolites. Over 22,000 postbiotic metabolites have been identified thus far. Some of the key functions of postbiotic metabolites include anti-inflammatory activity, create a slightly acidic pH in the microbiome ecosystem, which inhibits the growth of pathogens and promotes the growth of probiotic bacteria, they send signals to the brain, which influence mood, appetite and satiety, and much more.
Direct delivery of postbiotic metabolites is a much faster, more effective way to reduce the symptoms of dysbiosis and improve overall digestive health compared to just administering probiotic bacteria. In order to be effective, probiotic bacteria must make postbiotic metabolites.
Pande: At Sabinsa, digestive health is one of the top areas of research interest. Digezyme, LactoSpore, LactoWise, LactoCran, Saberry and DGL are a few of Sabinsa’s ingredients backed by science and clinical studies. LactoSpore and DigeZyme definitely would rank as the top two products in this segment.
LactoSpore is a probiotic containing Bacillus coagulans MTCC 5856 strain bacteria, which is well researched and clinically studied for gut health. In the clinical studies, LactoSpore has also shown its beneficial effect on the gut brain axis, which is an area of great interest. One of the reasons why LactoSpore has been considered as a probiotic of choice is its low dosage is owing to its better viability than most of the other probiotic bacterial strains.
The bacillus strain in LactoSpore is a spore-forming strain, that protects itself from the low pH acid in gut during the gut transit. It also is protected from the manufacturing stress while making tablets, gummies or other formulations where it is exposed to both low pH and high temperature. Clinical studies on LactoSpore show that this strain of bacteria can support healthy microflora and support healthy digestive health overall. LactoSpore is also a GRAS (generally recognized as safe) ingredient, and couples with its stability under extreme conditions makes it a popular ingredient in functional foods and beverages.
Burton: A search for recent research shows that there have been 16,284 published studies on probiotics since the beginning of 2020. Where many probiotic companies buy in their bacteria strains, Bio-Kult Original is formulated with its own PXN strains, meaning the clinical research is based on the finished product opposed to the strains alone. Bio-Kult Original has been used in recent published studies such as the largest clinical study in IBS-D, migraine and most recently in low mood.
Schneider: I believe it is very important to look at the whole microbiological system. This means not only taking only probiotics, prebiotics, and postbiotics but also providing nutrients that support a healthy gastrointestinal lining and incorporating food-derived antioxidant compounds to aid in protection from intestinal oxidative stress and alleviate inflammation. Ingredients such as curcumin and boswellia, which are clinically backed, provide this protection.
Digestive Vibrance from Vibrant Health provides these ingredients and more making it a comprehensive formula supporting the entire microbiological system.
Mak: Depending on their children’s needs, parents may select the following two products offered by ChildLife Essentials to support their children’s digestive health. ChildLife Essentials has formulated both ChildBiotics Probiotics with Colostrum and LiveBiotics Immune & Digestive Support for healthy growth and development in children.
Both products consist of bioactive ingredients, such as probiotic strains Lactobacillus acidophilus DDS-1 and Bifidobacterium lactis UABla-12, that exhibit gut-supporting abilities as well as immunomodulatory effects. DDS-1 and UABla-12 have been clinically researched for their physiological interactions with the gut-immune axis. DDS-1, alone or with UABla-12, can modulate gut microbiota by increasing the relative abundance of beneficial bacteria and reducing levels of opportunistic bacteria. In addition to improving bowel habits, stomach discomfort, and quality of life, this combination of DDS-1 and UABla-12 can help promote healthy immune responses, reducing inflammation induced by environmental substances and supporting pediatric development.
ChildLife Essentials ensures that these pediatric dietary supplements contain only the highest-quality ingredients while committing to the top standards for an all-natural, clean and sustainably sourced brand for informed consumers.
Both ChildBiotics Probiotics with Colostrum and LiveBiotics Immune and Digestive Support are free of artificial colors, flavors and sweeteners and are formulated with delicious, kid-approved, natural fruit flavors. ChildBiotics Probiotics with Colostrum is made in a ready-to-mix powder form to add in food and drinks for infants and children to easily consume; this product blends the natural sweetness of fresh colostrum with a natural tropical orange flavor while providing a unique combination of health-promoting probiotics and first-milking colostrum in a single serving. LiveBiotics Immune & Digestive Support is free of the top nine allergens (wheat, fish, milk, peanuts, soy, tree nuts, shellfish, eggs and sesame), preservative-free, non-GMO, vegan and sugar-free; this product is naturally sweetened with a delicious natural berry flavor and formulated specifically for children beginning at age 1 year through their teen years. Both products are gluten-free and contain no egg, soy and wheat.
Billingslea: Our most popular gut health products are our Betsy’s Basics (store brand) probiotics. We have a variety of them to meet specific needs. Our 35 Billion and Women’s 50 Billion are our two most popular.
For digestion, our Betsy’s Basics Superzymes is the most popular enzyme. We also have our Betsy’s Basics Aloe Vera Plus: 1 cap equals 2 oz. of Fresh Organic Aloe, and the Plus includes marshmallow root and slippery elm bark. Betsy’s Basics Triphala is another must for digestion support. Our Betsy’s Basics Ginger and DGL products are also an important part of our gut health and digestion category.
Natural Factors Gastro-Assist is another popular product in this category.
VR: Prebiotics—carbohydrates, resistant starches, pectins, etc.—have become very popular. Please cite one or two of your favorite science-validated prebiotic ingredients or formulas.
Schneider: Pomegranate is a great prebiotic because it stimulates the growth of gut bacteria and is protective against degenerative diseases. Larch arabinogalactans are a great source of dietary fiber that stimulates the growth of beneficial bacteria along with support for digestive health.
Bruno: One downside to prebiotics is that several grams (5 or more) are typically required in order to provide clinical benefit. There is, however, one exception to this: PreticX branded xylooligosaccharide (XOS) from AIDP, which have been shown to provide prebiotic benefits with just a dose of about 1 g. This was demonstrated in a double-blind, randomized, placebo-controlled study in which XOS was tolerated without significant gastrointestinal side effects, and bifidobacterium counts increased significantly.
Burton: Beneficial lactobacilli and bifidobacteria are more efficient at fermenting these prebiotic foods than pathogenic strains (meaning they stimulate their growth) and produce a lot less (if any) gas during fermentation.
A 2022 study concluded that FOS supplementation could increase the number of colonic Bifidobacterium spp. while higher dose (7.5–15 g/d) and longer duration (>4 weeks) showed more distinct effects and was well tolerated.
However, initially, until levels of beneficial species are increased, prebiotics can cause bloating in some people so it’s best to introduce prebiotic foods or a prebiotic supplement gradually. Monheit: This category is more than just probiotics—prebiotics have gained traction because they meet the need to nurture and support the microbiome full stop. Also, new developments mean lower dosages, ease and convenience. Resistant starch like Solnul, GOS (Clasado’s Bimuno), Anagenix (Livaux) are some with strong clinical substantiation, and across the board the science is increasing in this category.
Pelton: Balance and diversity are critical for microbiome health. Taking large amounts of a prebiotic may be helpful. However, ingesting a large dose of a prebiotic actually works against balance and diversity. People should strive to eat small amounts of many different types of prebiotic foods daily. This promotes the growth of a diversity of probiotic bacteria, which in turn, will produce a diversity of health-regulating postbiotic metabolites.
VR: We know that probiotics are big—especially considering the gut-brain axis, and now also the gut-bone axis—briefly cite one or two of your favorite science-validated probiotic ingredients or formulas.
Burton: The probiotic supplement Bio-Kult Original was recently used in a study at the University of Oxford on low mood and emotional salience. This was a double-blind placebo-controlled trial in 70 people who were experiencing low mood, half were given a placebo and the other half were given the Bio-Kult probiotic blend. They were taking two capsules twice a day for a month and the participants reported their mood via a Patient Health Questionnaire for Depression. The result from the documentary showed a 20 percent improvement in mood for those in the placebo group versus a 50 percent improvement in mood in those taking Bio-Kult. The supplement group also reported a 50 percent improvement in their concentration.
In terms of the gut-bone axis, a 2020 review highlighted how modulation of the gut microbiota is an attractive therapeutic intervention to counteract bone loss. The review looked at iron, selenium, zinc, calcium and vitamin D along with prebiotics, probiotics, postbiotics and synbiotics and suggested these interventions should be explored further as useful adjuvant treatments for osteoporosis.
Pelton: I would call out Dr. Ohhira’s Probiotics, which contains probiotics, prebiotics, and most importantly, over 500 postbiotic metabolites.
Pande: LactoSpore that has undergone clinical studies for management of gut health with specific focus toward the gut brain axis-related health conditions. In two studies which included subjects with irritable bowel syndrome, LactoSpore was supplemented at 2 billion spores/day. Clinical results showed not only improvement in gut health—such as intestinal pain, and bloating, which are common occurrences in such patients—but also improvement in major depressive disorder, or in other words positive mood benefits. IBS is a gut-brain-axis-related health condition and improvement in the clinical parameters showed direct benefit of LactoSpore on gut-brain axis. All the studies on LactoSpore were carried out at 2 billion spores/day.
Brix: The gut is connected to everything, and new research is revealing that many axis exist throughout the body. In terms of the gut-brain axis, certain probiotic formulas have been shown to help moderate general feelings of anxiousness, promote a healthy mood balance and relieve stress-related gastrointestinal complications.
One double-blind, placebo-controlled, randomized, parallel group study of healthy adults who took 3 billion colony forming units of Bifidobacterium longum subsp. longum (R0175) and Lactobacillus helveticus (R0052), showed decreases in scores on two psychological distress tests. Average urinary levels of the stress hormone cortisol also decreased, and a follow-up study found that those with the lowest baseline cortisol levels had the most significant improvements in scores related to mood and feelings of anxiousness.
Mak: Lactobacillus rhamnosus LGG and Bifidobacterium animalis subsp. lactis BB-12 are well-known probiotic strains that have been clinically studied in infants and children. Administration of LGG in children has demonstrated fewer incidences, shorter episodes of loose and watery stools, and normal bowel habits. In relation to immune challenges related to respiratory health, LGG has been associated with fewer respiratory challenges and significantly fewer days with signs of respiratory discomfort. BB-12 was shown to be associated with softer and more frequent bowel movements, shorter and fewer episodes of loose stools, and overall regularity. In one clinical study, BB-12 supplementation among healthy, full-term infants resulted in better gut immune response. BB-12 may also reduce the duration of crying in fussy infants and thus significantly improve the quality of life for parents and caregivers. Based on these findings, ChildLife Essentials has formulated InfantBiotics Probiotic Drops with both proprietary probiotics LGG and BB-12 to reduce stomach discomfort and duration of loose stools in infants and children.
VR: Postbiotics must be part of the conversation, too, especially considering the newer entries geared to support digestive, immune, and skin health; briefly cite one or two of your favorite science-validated postbiotic ingredients or formulas.
Green: Each postbiotic is unique, based on the microorganism, the fermentation medium and method used, the post-fermentation process, and its ability to confer a health benefit on the host. Cargill’s postbiotic, EpiCor, is backed by over 75 years of fermentation expertise. It is made using baker’s yeast (Saccharomyces cerevisiae) that goes through a natural fermentation process, which creates a unique fingerprint of metabolites. After the fermentation process, it is gently dried using a proprietary heating process that kills off the yeast, while still preserving all the metabolites and functional compounds. Over a dozen published studies, including multiple human clinical trials, show that EpiCor postbiotic supports the gut microbiome, as well as immune health and nasal comfort.
Human clinical research has shown that EpiCor postbiotic helps positively modulate beneficial bacterial populations and, in model studies, may support short chain fatty acid production, effects that highlight how the ingredient can play an important part supporting the gut microbiome.
EpiCor postbiotic was first established in the supplement space, but our application scientists have found it’s a good fit for functional foods and beverages, too. Its recommended dose is just 500 mg per day, making it easy to formulate into a wide array of functional products, including gummies, nutrition bars and beverage shots.
Burton: A favorite postbiotic is heat-treated Bifidobacterium longum ES1 bacterial strain which has been shown to have the capacity to protect against oxidative damage, as well as inhibit bacterial colonization, by activating biological pathways related to our innate immune function.
Due to its anti-inflammatory/antioxidant profile, this strain has also been used in probiotic formulations shown to improve symptomatology derived from atopic dermatitis, psoriasis, and asthenozoospermia—conditions which are related to damaged intestinal integrity.
Pelton: Butyrate is a critically important postbiotic metabolite. It has anti-inflammatory activity, it is the primary agent that supplies energy to colonic epithelial cells, and it enhances intestinal barrier function and mucosal immunity. Phenyllactic acid is a postbiotic metabolite that is produced by Enterococcus faecalis TH10. It has been shown to exert antifungal and antibacterial activity, especially against MRSA.
Monheit: We’re fans of LBiome from Stratum and Immuse from Kyowa Hakko.
Pande: Recently Sabinsa launched an innovative postbiotic preparation from its patented probiotic strain Bacillus coagulans MTCC 5856. This postbiotic, ImmunoSpore, has been studied for its immune boosting activity as well as anti-inflammatory activity. It was found that ImmunoSpore can upregulate the expression of inducible form of nitric oxide synthase (iNOS) that can improve the immune defense against pathogens. ImmunoSpore has been standardized to contains 15 billion inactivated spores.
Bruno: I like a postbiotic commercially known as Immuno-LP20 (by Mitsubishi). Research shows supplementation with 50 mg augments acquired immunity, especially Th1-related immune functions in healthy subjects, thereby improving the health-related QOL. Likewise, 50 mg of Immuno-LP20 was found to stimulate type I interferon (IFN) in humans given an influenza vaccine. This same dose was found to decrease upper respiratory tract infection incidence in healthy subjects, likely through augmentation of immunity. In addition, daily intake of Immuno-LP20 improved inflammation and lipid metabolism (including decreases of total cholesterol, and LDL cholesterol) in subjects at risk of inflammation.
VR: We know that synbiotics typically combine prebiotics and postbiotics, but there are also emerging finished products that combine prebiotics, probiotics and postbiotics, in some cases along with botanical complements. Please cite your one or two science-backed favorites.
Pande: Two of the synbiotic combinations that we manufacture as customized products are LactoWise and LactoCran. With these products we change the way synbiotics are formulated. The selection of prebiotic for any probiotic is an important process, as each bacterium may have different nutritional needs for growth. The prebiotic part of these formulations was screened for stability and their prebiotic activity against standard prebiotic fibers to [ensure a] high-performing synbiotic combination. Lactowise and LactoCran both show high stability and are sought after as synbiotic combinations containing clinically studied probiotic.
Pelton: Dr. Ohhira’s Probiotics, which contains probiotics, prebiotics and postbiotic metabolites. Interestingly enough, it is not really “new,” but has been on the market in the U.S. for over 23 years! The research and development of the product by Dr. Ohhira started over 40 years ago using traditional Japanese fermentation techniques in strict accordance with most advanced pharmaceutical standards and has led to the product being one of the most trusted and proven formulas throughout the world. Dr. Ohhira’s Probiotics has been studied extensively over that time period with published results in numerous professional journals (most often under the Japanese name for the product OM-X).
Monheit: Ritual Synbiotic+ and Seed DS-01 Daily Synbiotic are formulations with prebiotics, probiotics and postbiotics that have solid science behind them.
VR: What ingredients (or product types) were not mentioned but you would like to shine a spotlight on?
Burton: Beta-glucans are a group of fibers that are suggested to exhibit a wide range of potential health benefits; including immune support, weight management, cardiovascular support, mood support and overall improved wellbeing. Beta-glucans are fermented by intestinal bacteria, potentially altering the composition of the gut microbiota, favoring species that exhibit beneficial compounds; with immunomodulatory, anti-tumor, anti-microbial and anti-oxidant properties.
Beta-glucans may also be helpful in managing inflammation as described in a 2020 randomized controlled trial in 31 healthy adult males and females. Individuals took 250 mg of yeast beta-glucans or placebo for 13 days while taking part in a prolonged bout of heated treadmill exercise. Concentrations of pro-inflammatory cells in the intervention group were significantly lower than the placebo group.
Pelton: Glutathione is one of the most important multi-tasking compounds in biology. It is the most prevalent antioxidant in humans, it plays key roles in detoxification, it is critical for immune function and it expresses powerful anti-viral activity.
A unique strain of probiotic bacteria named Lactobacillus fermentum ME-3 synthesizes substantial amounts of glutathione. Thus, glutathione is a postbiotic metabolite produced by ME-3. Human clinical trials reveal that people taking ME-3 gain numerous important health benefits including reduced levels of oxidized LDL-cholesterol, lower levels of free radical production, a 26 percent increase in total antioxidant activity, and 49 percent increase in the ratio between reduced to oxidized glutathione. Animal studies report a reduction in glycation and improved insulin sensitivity.
Brix: There are two areas that I think deserve attention. The first we didn’t touch on is supplements for small intestinal bacterial overgrowth (SIBO). With SIBO, no matter how much fiber, prebiotics, probiotics, or postbiotics you use, it typically won’t be eradicated until an antibacterial protocol is followed. In fact, certain probiotics and prebiotics can really exacerbate symptoms of bloating and bowel changes, so herbal extracts and oils from herbs such as oregano, peppermint, barberry and garlic, as well as specific enzymes, are used to help eliminate the cause of this very common condition.
The second is bacteriophages. Bacteriophages are viruses and are the most abundant member of the gut virobiota. Evidence is mounting that they may provide protective immunomodulating and anti-inflammatory activity. Although we are a way off from supplementing with viral material, understanding the role of the virobiome is exciting and unearthing further intricacies of gut health.
VR: Where do you see the digestive health, microbial health or the combined categories evolving?
Green: Given how foundational digestive and microbial health is to overall well-being, we expect demand for products that support gut health to continue their upward trajectory. In particular, we see plenty of upside for postbiotics. Our proprietary research finds half of U.S. shoppers are familiar with postbiotics—a great start for this relative newcomer to the consumer space. As we continue to invest to build consumer awareness for the category and our ingredient, EpiCor postbiotic, we expect this number will continue to grow.
Pande: The digestive health category is definitely going to stay strong, it is quite possible that microbiome related category will diversify from digestive health to immune, sports, cognitive health, as studies on microbiome are expanding understanding of the effect of the gut microbes on all these areas apart from digestive health.
Pelton: I believe that interest in digestive health and microbial health will grow substantially in the coming years as people learn more about the critical role the gut microbiome plays in regulating many aspects of health. I have written an article titled “The Microbiome Theory of Aging,” which has been accepted for publication in a medical journal. The article explains why microbial imbalance and microbiome dysfunction cause intestinal permeability (leaky gut), which results in many health problems and the acceleration of biological aging.
Burton: The next few years will see interesting and exciting developments in the microbial health market with companies investigating novel ways of providing probiotics to consumers. A study in September 2022 looked at whether it could be beneficial to intervene in environments within which children live to ensure exposure to more varied microbes at a young age. The study investigated whether it was possible to enhance gut microbial diversity and richness in children through environmental interventions by looking at the environments of day care and nursery facilities as a source of microbial exposures at this crucial time of life.
The study was the first of its kind—it was a placebo-controlled, double-blind study on the effect of environmental exposures on gut microbiota diversity and immune parameters in young children. Playground sandboxes at day care centers in Finland were used as sources of environmental microbial exposure with some sandboxes being placebos and some having a microbial powder added to them. Researchers measured the composition of gut and skin microbiota, as well as blood immune markers. Altogether, 26 children ages 3–5 participated in supervised play for 20 minutes in the morning and afternoon for two weeks.
The results showed that the microbially enriched sandboxes enhanced both the bacterial richness and diversity of the children’s skin bacterial community and this enhancement was not seen in the placebo group children. The authors also found that the daily exposure to higher microbial biodiversity resulted in positive differences in immune response. Therefore, the researchers concluded that environmental microbiota may contribute to child health, and that adding microbiological diversity to everyday living environments may support immunoregulation.
This poses an exciting new possibility. Will we start to see environmental probiotics (such as probiotic toys, bedding or playgrounds) being developed in the future?
VR: Is there anything else you would like to add?
Pelton: Postbiotic metabolites are the new frontier in microbiome science. For decades, companies have been creating and marketing products with one or multiple stains of probiotic bacteria. However, a substantial shift is beginning to take place. The food, cosmetic and natural products industry are committing more money to develop products based on postbiotic metabolites. In general, postbiotics are easier to transport than probiotic bacteria. In addition to being are more stable during transportation, postbiotics have a longer shelf life than probiotics. Since postbiotics do not contain live organisms, they pose less health risks than probiotics.
It often takes a long time for new scientific ideas to become accepted. For example, it took decades for Newton’s laws of physics and Einstein’s Theory of Relativity to be accepted. The postbiotic revolution is underway. Postbiotic metabolites regulate the microbiome ecosystem. Multiple factors can cause microbial imbalance in the GI tract (antibiotics, poor diets, stress), which causes intestinal permeability, many health problems and the acceleration of biological aging.
Dr. Ohhira’s Probiotics, with over 500 postbiotic metabolites, is one of the best products to help create and maintain a healthy microbiome. VR
Extra! Extra!
