An industry panel offers their insights.

The panel:

Abdul Alkayali, Vice President, Sales and Marketing, Longevity by Nature, Temecula, CA, www.longevitybynature.biz

Ramona Billingslea, Marketing Manager, Betsy’s Health Foods, Spring, TX, https://betsyhealth.com

Liz Cooper, Technical Advisor, Bio-Kult/ADM Protexin, Miami, FL, www.bio-kult.com

Slawek Gromadzki, MPh, Nutritionist, HealthAid America, Sunnyvale, CA, www.healthaidamerica.com

Neil Levin, CCN, DANLA, NOW, Senior Nutrition Education Manager, Bloomingdale, IL, www.nowfoods.com

Jay Levy, Director of Sales, Wakunaga of America, Co., Ltd., Mission Viejo, CA, https://kyolic.com

Ross Pelton, RPh, PhD, CCN, Director of Science & Education, Essential Formulas, Farmers Branch, TX, https://essentialformulas.com

Jodi Schneider, National Educator, Vibrant Health, Shelton, CT, https://vibranthealth.com

We now know that there is a bi-directional relationship between the brain and the gut, critically involving the vagus nerve, in this way connecting the 100 billion neurons in the brain with the 500 million neurons in the gut.

Since a rapidly growing body of science is being utilized to develop an ever-increasing range of gut-brain-axis-supportive products, we at Vitamin Retailer invited a panel of industry experts for their insights.

VR: How important is the gut-brain axis, and why?

Billingslea: As a person who lives with anxiety and depression, I understand all too well the connection between gut health and the brain. We live in a world that is moving too fast. The fast-paced lifestyle we live makes it difficult to eat the whole, organic foods that are required for one’s best gut health. Add to poor diet choices the toxins we encounter from the air and from things like plastics in our food supply, and you have the perfect storm to create the stressed-out majority of people dealing with the mental challenges bad gut health promotes.

Levin: It is passé to regard the gut and the brain as separate entities when both are directly connected within the nervous system via the vagus nerve. The so-called enteric nervous system consists of two thin layers containing more than one hundred million nerve cells lining the gastrointestinal (GI) tract all the way from the esophagus to the rectum. While the primary role of the enteric nervous system is to control digestive processes—everything from swallowing to the release of enzymes, to the movement of materials, and even the control of blood flow helping with nutrient absorption—its communication with the central nervous system (including the brain) also has meaningful results.

Alkayali: Spanning approximately 30 feet of tubular organs—encompassing the esophagus, stomach and intestines—that make up the GI tract serves as home to an interconnected community of thousands of microbial species, trillions of microbial cells and genes that influence virtually every facet of human health and wellness. Researchers have discovered profound associations between health and disease and microbiota composition and the functionality of these microorganisms. Specific gut microbial strains are believed to exert influence over metabolism, immune function, cardiovascular health, and—through the gut-brain axis—even mood and cognitive well-being.

Schneider: The gut-brain connection is a continuous loop. A good example of just how much our gut affects our brain is, that if we have pathogenic bacteria in the gut, those pathogens will create compounds that travel through the vagus nerve to the brain. In the brain, these compounds create panic, anxiety and stress. In turn, we develop symptoms like diarrhea or IBS from this feeling of anxiety or panic. Diarrhea sloughs off the beneficial bacteria in our gut, giving a chance for the parthenogenic bacteria to take over the real estate and multiply. This can create more panic or anxiety, which can also cause a leaky gut and more diarrhea, which creates a terrible loop because a leaky gut causes more anxiety, and so it goes.

Cooper: It is clear that the microbes which live in our gut play an important role in modulating the messages sent along the gut-brain axis. However, these messages can be disrupted in individuals who have an imbalance of beneficial and non-beneficial gut microbes, known as dysbiosis.

VR: What are the most critical nutritional ingredients to support both the gut and the brain? Give an example of a science-backed finished product that supports both.

Cooper: Bio-Kult Mind is one probiotic supplement that contains zinc as well as Bacillus subtilis PXN21, which has been found in an experimental study to not only prevent, but also reverse clumping of α-synuclein, a protein involved in neurodegenerative diseases such as Parkinson’s. In addition, Bio-Kult Mind contains grape and blueberry extract, consumption of which has been shown to improve episodic memory in healthy elderly individuals with lower levels of memory performance.

Levy: Probiotics, which are found in our Kyo-Dophilus line of products, can play a pivotal role in promoting a healthy gut microbiome while also influencing mental health. In one six-week trial, supplementing with probiotics reduced anxiety by 16 percent and stress levels by 20 percent. Another study found that probiotics significantly improved global mood along with reduced feelings of depression, tension, fatigue, confusion and anger in overweight and obese participants.

Another nutrient—and one that doesn’t readily come to mind when talking about the gut-brain axis—is Kyolic Aged Garlic Extract (AGE). Although there is no one study that addresses both the gut and the brain, in one study of this specific supplement, Australian researchers report that AGE improved gut microbiota, evidenced by higher microbial richness and enhanced diversity with a marked increase in lactobacillus species after three months of supplementation. In another preliminary study, researchers found that AGE reduced inflammation in the brain and improved short-term memory. Other research suggests that AGE also protects neurotransmitters like serotonin and dopamine in the face of acute stress.

Alkayali: KollaJell from Longevity by Nature is a patented nutritional supplement containing a first-of-its-kind jellyfish collagen (types I, II and V) designed to support cognition and brain health. It is rich in all 20 essential and nonessential amino acids, including glutamate, serine and tryptophan. They are vital for serotonin production and central nervous system communication. These molecules are recognized by gut receptors and are known to modulate the enteric nervous system and intestinal inflammation. More research is needed to understand these gut-brain interactions. KollaJell’s essential amino acids regulate glucose and lipid metabolism and energy balance, increase mitochondrial biogenesis, and maintain immune homeostasis.

Gromadzki: HealthAid America’s MoodProbio helps to supplement consumers’ diets by increasing levels of beneficial bacteria, by supporting the immune system, by assisting in the absorption of nutrients within the gut, and by boosting mood via […] special strains of acidophilus and bifidobacteria. MoodProbio also contains fructo-oligosaccharides (FOS) a prebiotic added to help support the growth of good bacteria in the gastrointestinal tract.

SleepProbio consists of carefully selected ingredients such as magnesium, 5-HTP, ashwagandha, theanine, GABA, passionflower, L-taurine and probiotic strains. The product’s probiotic blend (3 billion CFUs) features B. longum, L. acidophilus, L. helveticus that may help increase serotonin, dopamine and GABA (each involved in mood, relaxation and restful sleep) carefully selected for a particular action on the body to support gut health, good mood and restful sleep.

Levin: Probiotics are an obvious choice of nutritional ingredients to support both the gut and the brain; they are actually biologics as opposed to nutrients, though that is a technical distinction.

NOW’s Probiotic-10 formulas have live bacterial cultures that affect both the gut and the brain. One of the key specific strains contributing to this duality is Lactobacillus paracasei Lpc-37 (also known as Lacticaseibacillus paracasei Lpc-37).

Billingslea: I have had some genetic testing done which has led me to studying Bob Lynch’s Dirty Genes book. Much of my troubles seem to be connected to my inability to methylate. I think there are some promising finds as scientists continue to understand our genetics as well as our diet and lifestyle.

For people with mental health challenges, we work to get them on basic nutrients: a good multi, magnesium, zinc, D3/K2, a probiotic and fish oil. We also favor adaptogens such as ashwagandha or holy basil.

VR: What are the best diets and foods to support the gut-brain axis? What has the best science?

Levin: The Mediterranean diet and other legume-based diets have been shown to not only support healthy aging, but also to contain numerous dietary constituents that enhance both brain and gut health. Omega-3 fatty acids supply components of the nerve and brain cells while supporting healthy inflammatory responses. The foods in these particular diets also are considered high fiber; not only aiding in bowel regularity but supplying fermentable material for gut bacteria to digest.

Gromadzki: Consumers should go on a plant-based whole and unrefined diet [that is] high in dietary fiber (whole grains, beans, vegetables, fruits, seeds, etc.). Every day take the most effective supplemental prebiotics (chlorella, spirulina, psyllium husk, inulin, GOS, FOS, etc.). They are most effective in boosting probiotics because they create alkaline environment in the gut and are high in excellent quality fiber which nourishes friendly bacteria.

VR: The trillions of microbes that live in your gut that also make other chemicals that affect how your brain works, such as butyrate, propionate and acetate. Why is this important?

Gromadzki: The gut bacteria-producing metabolites like these short-chain fatty acids (acetate, propionate and butyrate) are often reduced in individuals with diabetes, obesity and autoimmune conditions. For this reason, probiotics being able to increase short-chain fatty acids, are helpful in benefiting people with the mentioned above health problems.

Levin: The digestion of fiber and so-called ‘resistant starches’ by gut microbes produces short-chain fatty acids (SCFAs), which are important nourishment sources for the energy-hungry cells lining the intestines. Without both probiotic bacteria and their food sources, the intestinal wall could weaken, negatively affecting its barrier function, raising the risks of food sensitivities and immune challenges.

Pelton: Intestinal permeability allows lipopolysaccharides (LPS) and other intestinal toxins to enter systemic circulation, which causes chronic inflammation, which damages the body and accelerates biological aging. This sequence of events has been explained in a paper titled “The Microbiome Theory of Aging.”

Cooper: SCFAs are metabolites which are produced by bacteria as a result of fermentation of fiber from our diet. One of these SCFAs, butyrate, has been shown to cross the blood brain barrier (BBB) where it helps to regulate the activity of certain brain cells thereby impacting brain development and behavior change.

VR: Gut microbes play an important role in your immune system and inflammation; please elaborate.

Pelton: If gut microbes are ‘fed’ a diversity of dietary fibers and polyphenols, they will produce a diversity of postbiotic metabolites that regulate the health of the gut microbiome ecosystem. It is estimated that 70 percent of the body’s immune cells are in the GI tract. Hence, a healthy gut is essential for a healthy immune system.

The intestinal tract is also a major source of inflammation, due to bacterial imbalance, which is caused by bad diets, antibiotics and numerous other factors.

Cooper: Many inflammatory processes have been found to stem from poor gut health. This is not surprising, as 70 percent of our immune cells (which play a role in the inflammatory response) reside within the lining of the gut and are supported by our beneficial gut bacteria. The gut microbiome, which consists of trillions of microorganisms that live in the intestines, doesn’t simply reduce inflammation but also helps the immune system to deliver a healthy balanced immune response and assists the body in returning to normal by supporting immune function throughout the body.

Levin: Research over the past 20 years has promoted the new idea that the appendix is a lymph-rich section of the intestines intended for exactly that purpose: both a boot camp for immune cells and a rebooting system for beneficial bacteria. While not absolutely essential for immunity, in healthy people the appendix does play a role in immune capability and function. Following that model, studies provide a more detailed picture of the communication between the gut microbiome and regulatory T-cells in the immune system. The gut microbiome also affects other immune cells such as natural killer T-cells by modulating their phenotypes and functions, such as activation by antigens.

Schneider: SCFAs, the main metabolites produced in the colon by bacterial fermentation of dietary fibers and resistant starch, are speculated to play a key role in neuro-immunoendocrine regulation in the hypothalamus, which is responsible for signals that control the production of hormonal output. VR: Gut bacteria that affect the brain, along with mood and stress, are often referred to as “psychobiotics.” Please elaborate.

Schneider: A psychobiotic is used to describe the commensal bacteria that play a role in the gut-brain axis and support brain health.

The gut produces 50–60 percent of the “feel good” hormones such as GABA, serotonin, and dopamine. When we are stressed, the limbic part of our brain acts as though we are having a life-or-death threat. This stress causes bowel irregularity which lowers the gut’s diversity and makes it difficult to produce these feel-good hormones that calm us down.

Psychobiotics are specific strains of probiotics that are shown to, directly and indirectly, produce positive effects on neuronal functions by colonizing the intestinal flora. Psychobiotics are generally considered to involve the hypothalamic-pituitary-adrenal axis, intestinal permeability, and inflammation.

I would recommend Zen Biome by Microbiome Labs.

Cooper: While still in their infancy, the hope is that psychobiotic products can be tailored to support a range of psychological and mental health issues. One such product is Bio-Kult Everyday, containing 14 different strains of live bacteria, which have been used in a variety of human clinical trials, an important aspect for deciding upon a supplement.

VR: Talk about the linkage between gut health and skin health.

Gromadzki: When harmful microbes are present in the body, this triggers the immune system to jump into action to fight back. The battle produces inflammation. Taking probiotics topically, internally or both is thought to calm that inflammatory response and reduce the incidence of acne and other inflammatory skin conditions.

HealthAid SkinProbio is a unique formulation containing a superior blend of 35 billion CFUs with carefully selected nine different probiotic strains, each one carefully selected for a particular action on the body to support skin health. It is also fortified with a prebiotic (FOS) to further benefit skin and help stimulate the proliferation and survival of beneficial bacteria.

Schneider: The first thing to do is to heal your intestinal lining and support your gut health with a good probiotic that includes ingredients that also help heal the gastrointestinal lining. The next thing you need is omega-3 fats. Your skin is so critically dependent on omega-3 fats for health. Also, make sure your nutritional levels are good. Lots of nutrients play a role in skin health like zinc. If zinc is low, for example, it can contribute to eczema, acne, and other rashes. Vitamin D plays a huge role in things like psoriasis and acne. So, get a good multivitamin, good fish oil and good vitamin D3. It is also good to get your blood circulation going along with exercise and sweating, which will help remove toxins.

I recommend Trilogy and Vibrant Health from Vibrant Health.

VR: What about prebiotics, postbiotics and synbiotics? Where do they fit in here?

Levy: recent studies suggest that pro- and prebiotics may modulate the gut-brain axis and lower the incidence of some neurological conditions such as depression, anxiety, and even Alzheimer’s disease. Some probiotic supplements also include prebiotics. These products, which are known as synbiotics, have been shown to improve both the microbiome and gut immunity, while having the potential to support mental health. Adding an appropriate prebiotic to clinically studied probiotic strains creates a revolutionary solution to conveniently and effectively improve both the user’s digestive health and their immune response. Such a solution can be found in our Kyo-Dophilus Pro+ Synbiotic.

Levin: Synbiotics are simply combinations of probiotics and prebiotics. This is actually quite common in probiotic formulas, but it is important to know that the amount by weight of prebiotics that are effective will vary by the type. For example, it typically takes several grams of a FOS or inulin product to have the desired effect, while less than two grams of a type like XOS can be equally effective. So, it will be rare that the amount of prebiotic added to a synbiotic formula will be a clinically effective dose, though any amount may be somewhat helpful. It is also unusual that a probiotic formula containing a base of prebiotics will be labeled as a synbiotic formula; that term is not in general use on product labels.

NOW does offer products with XOS: a standalone powder that we call ‘Prebiotic Bifido Boost,’ which I add to my smoothies, and a ‘Probiotic-10 & Bifido Boost’ in veg capsules.

Gromadzki: Postbiotics are byproducts of natural probiotic bacteria fermentation. Postbiotics help growth and survival of good bacteria in the gut, help reduce inflammation, mimic effects of probiotics, kill pathogens, regulate hormone and insulin levels, and boost immunity. They are regarded as a good addition to probiotic supplements.

VR: What about good bacteria and energy metabolism?

Levin: Gut probiotics can actually generate short-chain fatty acids (SCFAs) by fermenting resistant starches and fiber that are normally not digested in the small intestine to be available for general energy in our bodies. This creates a sparing effect where these fermentation products (SCFAs) in the large intestine can supply energy to the gut cells to maintain the integrity of their barrier function. This supports immunity and tolerance to foods, as well. All of these processes in the body are energetic, and the ability to directly supply food sources to these energy-hungry gut cells allows more of the body’s energy to go to other needs including the heart, brain, metabolism, repairs and immunity. L-glutamine is another potential energy source for these cells in the gut, but it is also an alternate energy source for the brain; this is an example of the potential sparing effect of supplying energy to gut cells via fermentation of prebiotics rather than needing to use other types of nutrients for that purpose.

Cooper: A healthy gut lining is particularly important for the absorption of many nutrients from food that are required for energy metabolism. Low levels of inflammation in the gut caused by pathogenic overgrowth, or leaky gut can also have a negative effect on energy levels.

VR: How can retailers break down these complicated concepts and connections for their customers?

Billingslea: We work to educate our customers on diet and lifestyle factors as needed. As a retailer, I feel that we are limited by the products we have available. We have to work with what we have. That’s one reason it’s always so exciting to see our knowledge grow about things like our genetics and our microbiome and the kinds of products to support our nutritional needs manufacturers develop accordingly.

Most customers seem pretty familiar with the gut-brain connection when we bring it up, which certainly helps make our job of explaining things to them much easier.

Levy: While a knowledgeable staff member may be able to quickly simplify the concepts of probiotics (the benefits of having more “good” bacteria than “bad” bacteria take up real estate in the gut) and prebiotics (the fibers that feed your good bacteria), a more in-depth explanation can be difficult at a retail level. However, educational booklets, handouts and blog posts do an excellent job of helping consumers understand their gut microbiome and the gut-brain axis, as well as how supplementation can help to optimize both. Wakunaga has these resources readily available to retailers and on their website at kyolic.com and at probiotics.com.

VR: What are your projections as to products and the market potential for gut-brain-axis-supportive nutrition?

Levin: This is an emerging and growing part of the probiotic supplement category. As time passes, we will see more and more studies showing the relationship of specific probiotic strains to benefits beyond gut health. The direct physical connection between nerve cells in the GI tract and nerve cells in the central nervous system is the mechanism by which the observed connection between mood and digestion occurs. I expect to see an expanding list of trademarked and patented probiotic strains that have supporting science to affect mood, memory and other functions previously attributed solely to the brain.

Cooper: According to some sources, the global market for psychobiotic supplements in particular is expected to expand from over $140 million in 2023 to almost $202 million by 2033. The growth and market share in North America is particularly significant, estimating a CAGR (compound annual growth rate) of 11 percent between 2021 and 2028, as awareness of and investment in these products grows, alongside an increasing prevalence of mental health disorders.VR

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