Beyond Probiotics

ARTICLE SOURCE: https://wholefoodsmagazine.com/front-page/beyond-probiotics-pre-syn-post-and-psycho/

Julia Peterman
May 22, 2019

Catching up with Gut Science

Probiotics are a popular topic these days—Google Trends shows that searches for “probiotics” have doubled over the past five years. But they’re only the tip of the iceberg, and, according to Google Trends, the rest of the iceberg is way underwater. Prebiotics receive less than a tenth of the searches that probiotics do, and psychobiotics, postbiotics, and synbiotics all get the same number of searches: zero.

In this article, we’ll go through the science, so you can pass it on to curious customers. But because it’s difficult to talk about how these all fit together without talking about all of them at once, here’s a quick-and-dirty rundown:

• Probiotics are live bacteria that confer a benefit upon the person who ingests them; they live in our stomachs and help us digest food.
• Prebiotics are what the probiotics eat: They’re fibers that come from foods like chicory root, garlic, and Jerusalem artichokes.
• Synbiotics are compounds made up of a probiotic and a prebiotic that selectively favors said probiotic.
• Postbiotics are either dead probiotics or the metabolic byproducts of probiotics (1).
• Psychobiotics are pre- and probiotics that affect the gut-brain axis—i.e., those products that can aid in mood regulation (2).

That said, according to Ivan Wasserman, managing partner at Amin Talati Upadhye, Chicago, IL, these definitions aren’t regulated. “Probiotics have the best definition,” he says. “Key to that definition is that they’re alive and provide a health benefit. But the other terms aren’t defined by the FDA.” At the moment, it’s largely a non-issue—prebiotic is the only other term used regularly, and we’ll discuss how to identify those in this feature. The other terms are largely unknown to consumers, so Wasserman recommends that products labeled with these terms “devote some of that label space to an explanation.” In the meantime, it’s not a bad idea to tell your customers about them anyway, so that when these terms become more mainstream, your customers are already in-the-know.

Probiotics
We’ll start with the biggie. Probiotics are, as mentioned earlier, beneficial bacteria. The top use is as a digestive aid. Quantity is a well-known measure of quality, and, in some cases, a useful one: According to Jery Cochern, founder and president of R&D at Pure Essence, Las Vegas, NV, “Part of quality is quantity. With a total probiotic population of up to 100 trillion cultures in a healthy gut, 100 billion cultures are still only 1/1000th of that desired population. Those with visible signs of probiotic depletion should probably use very strong formulas. It is the only way to even begin to replenish that vast population in any kind of reasonable time frame.”

That said, quantity is just one measure of quality. Trisha Sugarek MacDonald, BS, MS, senior director of R&D and national educator at Bluebonnet Nutrition, Sugar Land, TX, notes that “science has shown that quantity should not always be the priority,” Sugarek Macdonald says. “It’s important to understand the quality of your probiotic, and each strain’s specific applications.” Other important things to look for, she says:

• Scientifically supported probiotic strains: A single probiotic may have many different strains, each of which perform different functions. This is related in a big way to postbiotics: Different bacteria produce different metabolites, which serve different purposes. So no, a probiotic formula intended to aid in sleep is not interchangeable with one intended to aid in immune health.
• DNA verification: “DNA identification is the only way to ensure that you’re getting the most effective probiotic strains,” Sugarek MacDonald maintains. “Not all strains are created equal.” She notes that Pasteur Institute is dedicated to the study of microorganisms and the characterization of the DNA sequence of each strain.
• Symbiotic probiotic strains: Probiotic strains can kill off other strains, Sugarek MacDonald notes, so not only is it important for the individual strains to be scientifically proven—the whole formula has to be tested to ensure that the strains inside are compatible with each other.
• Made to survive: Probiotics have to survive manufacturing and stomach acids. The manufacturer you buy from should be transparent about what methods were used to keep those probiotics viable.

Sid Shastri, product development manager at Kaneka North America LLC, based in Pasadena, TX, adds to this list the qualifier actual trial dosage. “It is not uncommon to find that a commercial probiotic product does not line up exactly with the amount and format of the strain that was utilized in the clinical trial,” he contends.

And when it comes to survival, Leah Nicolo, director of marketing at Enviromedica, Austin, TX, contends that spore-based organisms (SBO) are best: “Non-SBO probiotic supplements are made from fragile, lactic acid-based organisms that are killed off by acid, heat, and light. SBOs are inherently resilient, protected by a natural seed-like structure so they survive their journey from manufacturing to store shelves to the gut.”

John Deaton, VP of science & technology at Deerland Probiotics & Enzymes, notes that these spore-forming bacteria have a variety of benefits beyond their resilience. “B. subtilis and its relatives can persist in the GI tract, increase its numbers and then re-sporulate; block bacterial pathogens from colonizing, thereby maintaining a healthy probiotic community; communicate with intestinal cells to maintain healthy gut barrier function; and increase immune reaction of intestinal cells.”

And if you’re looking for a genome sequenced strain, DE111 B. subtilis is one. How can you be sure? “Through Deerland’s partnership with Cornell University,” Deaton says, “DE111® B. subtilis has been fully sequenced for safety and has been uploaded to GenBank, the National Institutes of Health genetic sequence database.” You can ask for proof, he says, that the strain has been uploaded to GenBank as one method of verification.

It’s also worth noting that, according to Wasserman, probiotics are unique ingredients on a strain level. “Each new strain needs to be individually declared GRAS,” he says. This makes sense on a scientific level, according to Shastri. “Strains refer to individuals of a given species that have specific traits that set them apart from other individuals from the same species,” he says. He uses Lactobacillus plantarum as an example: “We at Kaneka selected three very specific strains of L. plantarum that had the most potent effects on lipid metabolism and bile salt hydrolysis activity, which we use in Floradapt Cardio. Other strains don’t have the same lipid-modifying effects.”

Deaton concurs, and notes that this is another reason why genome-sequencing is so important. “It unlocks what each gene in the DNA genome does, how the genes interact and how the various parts of the genome are coordinated. By mapping out and revealing the DNA contained within the bacteria, we can identify any bad genes or antibiotic-resistant genes it may contain. The former may exert health issues while the latter is capable of being transferred between bacteria in the gut.”

This is how products with proprietary blends come to be: For instance, the Kyo-Dophilus Probiotics from Wakunaga are made with what the company calls “The Friendly Trio”: Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and B. longum MM-2. The trio has been shown to support digestion, allergy symptom, and a healthy microbiome—but other strains, even from the same genus and species, may not do the same.

None of this should be a problem if you’re ordering from a reputable manufacturer, but it is worth pointing out to any customers considering ordering from Amazon, where products aren’t necessarily vetted as stringently.

You also may want to consider talking to older customers about what probiotics can do for them: Andreas Koch, marketing director at Pure Essence, says that as we age, our microbiome naturally changes. “Research shows that aging, along with antibiotics, oral contraceptives, many prescription drugs, chlorinated water, and more can deplete the probiotic cultures that inhabit the human gut. Those 40 years or older typically have greater depletion than younger people.” He adds that a good balance would be around 53% Bifidobacterium and 47% Lactobacillus.

Speaking of antibiotics, they’re being prescribed more and more often, and can deplete the microbiome. Probiotics like Pure Essence’s Restore formula can come in handy here, too–and not just after the fact: “Some may ask if antibiotics negate the value of using probiotics,” Cochern says. “Undoubtedly, they diminish the value, but studies have shown that even a transient presence of probiotic supplementation provides benefits.”

Moving beyond digestive health, probiotics are great for immune support—you already know this, but it’s worth repeating. “No matter what the specific disease condition is,” says Greg Cooper, director of business & product development with Jackson GI Medical/Prebiotin, Camp Hill, PA, “ultimately, the solution to illness brings us back to gut bacteria. As much as 80% of our entire immune system is in our gut! With the right balance of bacteria,” he notes, “we are protected from pathogens and illness throughout our system, whether the illness is asthma, bronchitis, or an ear ache.” Given a poor diet, the microbiota, Cooper says, “are no longer resilient or diverse enough to stimulate an effective immune response,” leading to gut dysbiosis and an increase in all disease conditions. Just as the immune system begins in the gut, your customers may find it useful to start their journey to immune health in the probiotics section.

Probiotics don’t end their usefulness there. Start thinking skin. Belle & Bella has a Skin Therapy product based on clinical studies—the probiotic strains and the number of CFUs in the product are clinically proven. “Our gut and our skin are the two largest organs of detoxification in our body,” says Alan Cheung, executive director at Belle+Bella, Lexington, MA. “If our gut is out of balance, it will manifest on our skin. This is known as the skin-gut axis.” The skin-gut axis was first proposed around 80 years ago, by John H. Stokes and Donald M. Pillsbury (3). It has been thoroughly validated since then: a 2008 study involving 13,215 Han adolescents found that gastrointestinal dysfunction was “an important risk factor for diseases of the sebaceous glands, correlated with their occurrence and development” (4). Customers looking for help with skincare woes might want to start with a probiotic.

There’s also oral health. We know about the bad bacteria that makes up plaque and creates bad breath; Why not think about good bacteria? And not the same good bacteria that resides in the gut, either: According to Shastri, “Bacteria which are good colonizers of the intestine can be poor colonizers in the oral cavity, and vice versa.” Kaneka provides Floradapt in a gum health formula, comprised of three clinically supported symbiotic strains. Shastri notes that, unlike digestive probiotics, probiotics intended for the oral microbiome “have to be released in the mouth and stay there, as bacterial translocation from the gut to the mouth is null.” Oral probiotics tend, therefore, to be chewable instead of swallowable: chewing gum or lozenges instead of capsules or soft gels.

Stratum Nutrition supplies Streptococcus salivarius K12, a good oral bacteria, as BLIS K12 to formulators, which can support oral health, as well as ear, nose, and throat health.

And while we tend to think of probiotics as an inside-out kind of thing, there’s nothing stopping them from being just an out kind of thing. Desert Essence is now selling a probiotic hand sanitizer—not postbiotic, probiotic. Christine Allmer, marketing director at Desert Essence, Hauppauge, NY, notes, “Good bacteria exist on our skin without damaging it and represent a system of protection that helps keep our skin in balance. There are communities of microorganisms on the skin, which—when balanced—help prevent the spread of germs.” Thus, she says, it makes sense to add these microbes to hand sanitizer: “Traditional hand sanitizers will kill most common harmful germs; however, in the process, they also kill the good bacteria which contributes to a microbiome imbalance, creating unhealthy, unbalanced skin.” The kefir probiotic used in their hand sanitizer, she says, helps support a healthy microbiome—and it’s food-safe, in case of oral contact.

When talking about probiotics with a customer, it’s useful to remind them that we didn’t always have supplements. A customer looking for a specific benefit might find supplements more useful, but functional foods can serve the same purpose: Feel Better Pops are made with whole fruits and GanedenBC30, for a summertime probiotic treat. For those just looking for a general boost, though, they can go through the grocery section. Sauerkraut and kimchi might not come with the precise strain and CFU count on the package, but they’re a good way to boost probiotic intake, as is yogurt. For those customers who have trouble with yogurt—the sugar count, the type of milk used—suggest homemade.

Homemade yogurt has several benefits. Cheung notes that it gives the maker total control: “The ingredients in yogurt should be “milk and cultures.” When you make your own, you can choose the type of milk you like, you can add fresh fruits, honey, or granola, and you can leave out the thickeners, preservatives, and artificial anything.” Because it’s fresh, too, it can have a higher probiotic count than ready-to-eat yogurt. An extra benefit includes sustainability: Homemade yogurt goes into a reusable container, reducing personal use of single-use plastic cups. Milk might not be the first thing your customers consider when they’re looking for more probiotics, but signs next to different types of milk suggesting that coconut milk would make sweeter yogurt or that almond milk brings a nutty flavor can plant that seed. Don’t worry about losing ready-to-eat yogurt sales—there will always be people without the time or inclination to go homemade.

Prebiotics
Ingesting good bacteria (or applying it!) is only half the battle: Bacteria need to eat. “A healthy microbiome,” says Ross Pelton, scientific director with Essential Formulas, Irving, TX, “requires two things: Probiotic bacteria and a diverse range of fiber-rich foods in the diet.” Anke Sentko, VP of regulatory affairs and nutrition communication at BENEO, Parsippany, NJ, specifies: “Prebiotics support digestive health and wellbeing by supporting good bacteria. They are food components that reach the large intestine and function there as preferred feed for a few specific beneficial microorganisms.”

Prebiotics are most commonly oligosaccharides—FOS, GOS, XOS, and inulin—but the definition also encompasses conjugated linoleic acid and polyunsaturated fatty acid, although they’re not as heavily researched in terms of prebiotic activity as oligosaccharides (5). And aside from that? “There are no other scientifically established prebiotics at this point in time,” Sentko says, “only potential candidates.”

Lauren Clardy, VP of branded ingredients at AIDP, City of Industry, CA, notes that this does, in fact, mean that no, fibers in fruits and vegetables do not necessarily have prebiotic benefits. “Prebiotics selectively grow the beneficial bacteria,” she emphasizes. Wasserman mentions that the definition also includes non-fibers. Prebiotic is not interchangeable with fiber.

Furthermore, while “beneficial bacteria” is usually considered to be species in the Bifidobacterium and Lactobacillus genera, those certainly are not the only ones: Just Thrive notes on their website that beneficial bacteria includes species like Akkermansia muciniphila, which promotes a healthy metabolism and fat loss, and Faecalibacterium prausnitzii, which can increase the production of butyrate (a short-chain fatty acid—check out the Postbiotic section for more information on that) and may support liver health.

The best source for inulin, XOS (xylooligosaccharides) and FOS (fructooligosaccharides) is chicory root, but they can be found in onions and garlic, too, among other foods. Sentko says chicory root fiber—the richest source of prebiotics; dried, it’s comprised of upwards of 67% inulin—has been demonstrated to increase Bifidobacteria in more than 30 human intervention studies, covering various ethnic groups, every age, different durations, and different intake levels. GOS (galactooligosaccharides) is found most in Jerusalem artichokes, and in smaller quantities in beans and lentils—but even in Jerusalem artichokes, it’s only 7.5% of the food’s weight.

It’s worth it to keep an eye on what falls into the prebiotic category. Just because oligosaccharides and the two acids are the only prebiotics we know of at the moment doesn’t mean they’ll always be the only ones. For instance: green banana flour is generally considered a prebiotic. It’s rich in resistant starch, which boosts digestive health and the microbiome in general. AIDP is now the official distributor for NuBana, so you can keep an eye out for green banana flour-fortified food and beverages to sell for general gut health.

Enviromedica is looking for another prebiotic in riboflavin. According to Nicolo, “Riboflavin has been studied as a possible prebiotic whereby it mediates oxygen stress in the gut, allowing for successful proliferation of beneficial bacteria. However, it is a nutrient primarily absorbed in the small intestine, never making it to the lower intestine, where it can do the aforementioned work. Terraflora allows for riboflavin to be produced at the site of absorption.” Is it necessarily a prebiotic? The International Scientific Association for Probiotics and Prebiotics (ISAPP) doesn’t currently include it, but one day it might.

Another example of a possible prebiotic comes from Artemis International, Inc., Fort Wayne, IN. Melanie Bush, director of berry science at Artemis, notes that polyphenols—flavonoids high in antioxidants, one of which is the well-known compound resveratrol—have been shown in several studies to have the “ability to positively modulate the composition of the intestinal microbiota.” One 2012 study she cites showed that anthocyanins—a type of polyphenol that serves as the color pigment in berries—“have a prebiotic-like effect by increasing the population of beneficial gut bacteria like Bifidobacterium spp. and Clostridium coccoides, while inhibiting the growth of more detrimental bacteria like Bacteroides spp. and Clostridium histolyticum.”

That being said, the words “prebiotic-like” are key. Bush notes that “There are two schools of thought in the polyphenol-gut connection. The first is that the active compounds in flavonoid-rich berries are behaving similar to a prebiotic. The second mechanism of action involves the bacteria of the gut breaking down the larger flavonoid compounds in berries into more bioavailable metabolites that directly impact the related inflammatory pathways in the body.” Again, not what you’d recommend as a prebiotic, specifically—but a good recommendation for general gut health, and a good reason to keep an eye on the prebiotic category.

Prebiotics are a great choice for people looking to kick their digestive health up a notch. Clardy says that “Globally, many people suffer from a variety of digestive disorders such as bloating, constipation, acid reflux, and many others. Prebiotics have an advantage over probiotics and enzymes, in that they can address the whole spectrum of digestive health conditions.” The company’s PreticX, for instance, “selectively feeds beneficial bacteria, without feeding the bad bacteria, causing a favorable alteration in the gut microbiome.” Clardy notes that it has been shown to boost levels of Bifidobacteria and Bacteroidetes fragilis, two beneficial strains, and to decrease levels of non-beneficial bacteria, leading to a gut-wide reconditioning (6). Feeding good bacteria the food they need also means that they can properly produce postbiotics, responsible for many of the benefits received from probiotics.

Last but not least, if you happen to sell a food product fortified with prebiotics—or something like Uplift Food’s Daily Uplifter, a powdered supplement—you can tell your customers that prebiotics don’t affect the taste of food. In fact, according to Sentko, inulin and FOS can maintain or actually improve taste and texture. FOS, she says, “can be used in conjunction with high intensity sweeteners to help mask undesired off-tastes.” Inulin contributes to a creamy mouthfeel. And, of course, there’s an increase in dietary fiber, which, as Pelton notes, is the number one nutritional deficiency in America, making supplements or fortified foods a painless way of getting an important dietary component.

Synbiotics
“Synbiotics” refers to any supplement containing both a pre- and probiotic. It’s a good idea to take these: “Prebiotics function complimentary to, and possibly synergistically with, probiotics,” Sugarek MacDonald explains. “Preliminary data suggests that combinations of pre-and probiotics can provide a positive impact on gastrointestinal health above and beyond what each individual component can provide separately.” And what the two can provide, she says, is a necessary intervention: “Preliminary evidence is emerging that pre- and probiotics may be useful in conditions including inflammatory bowel disease, allergies, poor mineral absorption, and vaginal and urinary tract infections.”

More science is necessary, Sugarek MacDonald says, but it looks promising. Most of Bluebonnet’s probiotic products are synbiotics, containing FOS; Dr. Axe sells Gut Formula, another synbiotic. Synbiotics don’t yet have much science behind them, but you can probably hold your breath on this one—it won’t be long before they do.

Postbiotics
The definition of postbiotics is in flux. Wasserman notes that it can refer to dead and decomposing probiotics, but it often refers to the metabolic byproducts of beneficial bacteria. Fermented foods generally already contain these byproducts; otherwise, they’re created when probiotics digest prebiotics. Generally, a HABA product that says it’s “probiotic” or “probiotic-derived” actually contains postbiotics—of either definition—unless it says otherwise. When purchasing these kinds of products, request clarification from the manufacturer regarding the claim.

According to an infographic from Essential Formulas (7), there are five general types of postbiotics, as per the metabolic byproduct definition:

• Nutrients—B vitamins, vitamin K, various amino acids
• Antimicrobial peptides—Natural antibiotics that suppress the growth of bad bacteria
• Short chain fatty acids (SCFAs)—Optimize the pH balance in the GI tract and suppress pathogens
• Carbohydrate-active enzymes—Help probiotics digest fibers
• Hydrogen peroxide—Suppresses the growth of Candida and other yeasts

Different postbiotics are created by different bacteria, making diversity crucial. “Numerous studies have demonstrated that prebiotic fiber like Prebiotin is fermented in the colon,” says Cooper, “and increases the activity of bacteria that produce SCFAs, especially acetate, propionate, and butyrate. An increase of SCFA is associated with reduced disease risk.” Backing Cooper up, researchers in Brazil published findings in April listing sodium butyrate as a bioactive compound that affects gene expression—including genes related to the development of certain cancers (8).

Postbiotics do, of course, have uses not related to cancer. “Butyrate also helps to regulate the body’s energy homeostasis, helps to maintain the regulation of food intake, and energy expenditure,” Cooper says. In other words: SCFAs, particularly butyrate, help regulate energy. “When you are balanced, you process calories efficiently, helping your body to work at peak efficiency. Eat a diet with minimal prebiotic fiber, and you will have fewer SCFAs. You will eventually feel less energetic, and won’t be able to function as effectively.” Are your customers looking for help keeping their energy up during the day? Point them towards your digestive health section.

How about immune health? Bush cites a 2017 study that found that feeding Clostridium orbiscindens flavonoids caused it to produce desaminotyrosine (DAT), which in turn strengthened immunity. “The presence of DAT actually helped to protect against damage from influenza through augmentation of Type 1 Interferon signaling and a reduction of lung damage,” Bush says. “Additionally, treatment with antibiotics can worsen influenza because the resulting loss of the microbiota interrupts the production of bioactive metabolites like DAT.” Again—point immune health hunters towards your digestive health section.

And, of course, postbiotics have a day job: Just keeping the microbiome healthy. According to Essential Formulas’ website, postbiotics are what let us thrive: “A robust, naturally diverse microbiome will make all the postbiotics a body needs. However, when fewer families of bacteria are on board, the variety of postbiotics is also reduced—and our vitality suffers. Eating fermented natural foods supports our intestinal bacteria and delivers postbiotics that they have made during fermentation” (9).

People looking for a specific benefit might want to look into specific strains. For instance, Just Thrive’s probiotic contains Bacillus indicus HU36, which produces antioxidants right in the digestive system. Enviromedica’s Terraflora supplement produces riboflavin, right where the gut can benefit from it the most.

So while you’re talking up pre- and probiotics, don’t forget to educate your customers on the oft-forgot heroes: the variety of vitamins, minerals, enzymes, neurotransmitters, immune-signaling compounds, and SCFAs that probiotics produce after fermenting prebiotics.

It’s possible to buy supplements with postbiotics included, too, for an immediate health boost. Dr. Ohhira’s sells a probiotic supplement that includes a postbiotic concentrate. Audrey Ross, senior national educator at Country Life Vitamins, Hauppage, NY, notes that Country Life’s CognitiveBalance prebiotic supplement contains a whole food fermentate: prebiotics and postbiotics, which, along with the Cognivia and NeuroFactor in the supplement, boosts the brain starting in the gut.

Psychobiotics
Psychobiotics are defined as probiotics and prebiotics which, when ingested, confer mental health benefits through interactions with commensal gut bacteria. The term was defined as such in a 2016 review by Amar Sarkar et al.; Previously, the definition did not include prebiotics, according to a 2013 study by TG Dinan, C. Stanton, and JF Cryan (2, 10). This is a new concept, and it’s not set in stone—Sarkar et al. suggest that the
definition be expanded to include “any exogenous influence whose effect on the brain is bacterially-mediated,” or any outside factor that works on the brain through the gut.

Ross agrees that psychobiotics comprise more than just pre- and probiotics. “Vitamins, minerals, amino acids, polyphenols, and other metabolites all play a role in keeping a healthy gut microbiome. There are trillions of microbes in the gut that are responsible for keeping the bad bacteria at bay as well as making numerous chemicals that affect how the brain works. These signals get scrambled whenever there is an imbalance in the gut microbiome.” So yes—vitamins and minerals and more may play a role in keeping the brain healthy, but they do so by keeping the gut healthy. By, in other words, being psychobiotics.

While the term and the concept are new, the gut-brain axis isn’t. Jarrow makes a product containing probiotics and GABA to support the gut-brain axis; Natural Factors makes a Calm Biotic. The fact that scientists are still codifying what it means to be a psychobiotic doesn’t mean we’re only now getting psychobiotics on the market—it just means that products geared towards the concept are going to find their way onto your shelves.

Probiotic Science is On the Rise
This isn’t the last you’ll hear about the microbiome; We’re not even in the home stretch. On the most basic level, probiotics will keep being necessary—a report from Transparency Market Research (TMR) found that the probiotics market will expand at 8.3% CAGR during 2018-2026, anticipating that it’ll be valued at $12,753.4 million by the end of 2026 (11). Understanding of how antibiotics can affect the microbiome, TMR reports, will drive that growth. “Probiotics is a big category, and there’s a lot of excitement around it,” says Wasserman. “It’s second only to CBD in terms of consumer interest.”

Beyond that, scientists haven’t yet found a limit to what the microbiome can do and how we can manipulate it, and they’re not done searching. Bush mentioned that one area she’s excited about is the combination of synbiotics with antioxidants: “Preliminary studies suggest that the incorporation of antioxidant compounds along with a probiotic could have cumulative benefits. For example, to investigate the functional outcomes of incorporating antioxidant compounds into the human gut, Roberts et al. (2016) measured the impact of a prebiotic-probiotic-antioxidant blend on endotoxin levels in humans pre- and post-triathlon. The treatment blend reduced endotoxin levels both pre- and post-race, compared to the synbiotic alone.”

Nicolo is excited about other combinations. “EnergyBalance contains elevATP to support the production of ATP. The combination of unique ingredients in SleepBalance helps the microbiome facilitate the body’s ability to produce neurotransmitters and get them to where they need to go. It’s about balance and the ability for clear signals to be sent between the gut and the brain.”

Applications for probiotics will continue to evolve, too. Deerland suggests to its customers the use of DE111 in foods: “The idea is to create a desirable functional food,” Deaton says, “To take what was once a “no no” food and use its nutritive value to blend with probiotics, creating a guilt-free, nutritious treat.” Deerland uses chocolate as an ideal food to blend probiotics with. Why? As Deaton explains: “The bacteria that thrive toward the end of the digestive tract—like B. subtilis—ferment both the antioxidants and fiber in the cocoa. Combining probiotics like DE111 with chocolate multiplies the benefits the chocolate provides, such as supporting healthy blood flow.” Pills and capsules are all well and good—but chocolate might be where probiotics go next.

Keep an eye on this market, and on the science that’s expanding its reach. Make good use of helpful resources like the Global Prebiotic Association and the International Probiotics Association, there to help raise awareness and educate stakeholders. And keep an eye on WholeFoods—we’re keeping up with this, as we have been since the beginning. WF

REFERENCES

1. J.E. Aguilar-Toalá et al, “Postbiotics: An evolving term within the functional foods field,” Trends in Food Science & Technology, 75, 105-114(2018). https://www.sciencedirect.com/science/article/abs/pii/S0924224417302765
2. Amar Sarkar et al., “Psychobiotics and the Manipulation of Bacteria-Gut-Brain Signals,” Trends in Neurosciences, 39(11), 763-781(2016). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5102282/
3. Whitney P. Bowe and Alan C. Logan, “Acne vulgaris, probiotics and the gut-brain-skin axis—back to the future?” Gut Pathogens, 3(1), 2011. https://gutpathogens.biomedcentral.com/articles/10.1186/1757-4749-3-1
4. H. Zhang et al., “Risk factors for sebaceous gland diseases and their relationship to gastrointestinal dysfunction in Han adolescents,” The Journal of Dermatology, 35(9), 555-561(2008). https://www.ncbi.nlm.nih.gov/pubmed/18837699
5. Glenn R. Gibson et al, “Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics,” Nature Reviews Gastroenterology & Hepatology, 14, 491-502(2017). https://www.nature.com/articles/nrgastro.2017.75#ref4
6. Michael Crane, “Xylooligosaccharide Prebiotic Improves Gut Flora in Pre-Diabetic Subjects, Study Suggests,” Nutritional Outlook. Posted 1/30/16. Accessed 4/29/19. http://www.nutritionaloutlook.com/blood-sugar/xylooligosaccharide-prebiotic-improves-gut-flora-pre-diabetic-subjects-study-suggests
7. “Explaining Postbiotics,” EssentialFormulas.com. Infographic. Posted 4/2018. Accessed 4/29/2019. https://essentialformulas.com/wp-content/uploads/2018/04/Simple-Postbiotic-infogragh.pdf
8. WholeFoods Magazine Staff, “Study: Curcumin, Resveratrol Possible Anti-Cancer Compounds,” WholeFoodsMagazine.com. Posted 4/23/19. Accessed 4/29/19. https://wholefoodsmagazine.com/news/main-news/study-curcumin-resveratrol-possible-anti-cancer-compounds/
9. “What are Postbiotic Metabolites? The Unsung Heroes of Our Health,” EssentialFormulas.com. Accessed 4/29/19. https://essentialformulas.com/explaining-postbiotics/
10. T.G. Dinan, C. Stanton, J.F. Cryan, “Psychobiotics: a novel class of psychotropic,” Biological Psychiatry, 74(10), 720-726(2013). https://www.ncbi.nlm.nih.gov/pubmed/23759244
11. “Global Probiotics Market to Reach US$12,753.4 mn by 2026, Driven by Increasing Demand for Diet Supplements,” Transparency Market Research. Published 3/2019. Accessed 4/29/19. https://www.transparencymarketresearch.com/pressrelease/probiotics-market.htm
12. “Biofilm Bacteria,” MPKB.org. Last Modified 1/11/2019. Accessed 4/29/19. https://mpkb.org/home/pathogenesis/microbiota/biofilm
13. Meng-Xin Hu et al, “Probiotics Biofilm-Integrated Electrospun Nanofiber Membranes: A New Starter Culture for Fermented Milk Production,” Journal of Agricultural and Food Chemistry, 67(11) 3198-3208(2019). https://pubs.acs.org/stoken/presspac/presspac/full/10.1021/acs.jafc.8b05024

ARTICLE SOURCE: https://wholefoodsmagazine.com/front-page/beyond-probiotics-pre-syn-post-and-psycho/

Julia Peterman
May 22, 2019

Beyond Probiotics: Pre-, Syn-, Post-, and Psycho-

Catching up with Gut Science

Probiotics are a popular topic these days—Google Trends shows that searches for “probiotics” have doubled over the past five years. But they’re only the tip of the iceberg, and, according to Google Trends, the rest of the iceberg is way underwater. Prebiotics receive less than a tenth of the searches that probiotics do, and psychobiotics, postbiotics, and synbiotics all get the same number of searches: zero.

In this article, we’ll go through the science, so you can pass it on to curious customers. But because it’s difficult to talk about how these all fit together without talking about all of them at once, here’s a quick-and-dirty rundown:

• Probiotics are live bacteria that confer a benefit upon the person who ingests them; they live in our stomachs and help us digest food.
• Prebiotics are what the probiotics eat: They’re fibers that come from foods like chicory root, garlic, and Jerusalem artichokes.
• Synbiotics are compounds made up of a probiotic and a prebiotic that selectively favors said probiotic.
• Postbiotics are either dead probiotics or the metabolic byproducts of probiotics (1).
• Psychobiotics are pre- and probiotics that affect the gut-brain axis—i.e., those products that can aid in mood regulation (2).

That said, according to Ivan Wasserman, managing partner at Amin Talati Upadhye, Chicago, IL, these definitions aren’t regulated. “Probiotics have the best definition,” he says. “Key to that definition is that they’re alive and provide a health benefit. But the other terms aren’t defined by the FDA.” At the moment, it’s largely a non-issue—prebiotic is the only other term used regularly, and we’ll discuss how to identify those in this feature. The other terms are largely unknown to consumers, so Wasserman recommends that products labeled with these terms “devote some of that label space to an explanation.” In the meantime, it’s not a bad idea to tell your customers about them anyway, so that when these terms become more mainstream, your customers are already in-the-know.

Probiotics
We’ll start with the biggie. Probiotics are, as mentioned earlier, beneficial bacteria. The top use is as a digestive aid. Quantity is a well-known measure of quality, and, in some cases, a useful one: According to Jery Cochern, founder and president of R&D at Pure Essence, Las Vegas, NV, “Part of quality is quantity. With a total probiotic population of up to 100 trillion cultures in a healthy gut, 100 billion cultures are still only 1/1000th of that desired population. Those with visible signs of probiotic depletion should probably use very strong formulas. It is the only way to even begin to replenish that vast population in any kind of reasonable time frame.”

That said, quantity is just one measure of quality. Trisha Sugarek MacDonald, BS, MS, senior director of R&D and national educator at Bluebonnet Nutrition, Sugar Land, TX, notes that “science has shown that quantity should not always be the priority,” Sugarek Macdonald says. “It’s important to understand the quality of your probiotic, and each strain’s specific applications.” Other important things to look for, she says:

• Scientifically supported probiotic strains: A single probiotic may have many different strains, each of which perform different functions. This is related in a big way to postbiotics: Different bacteria produce different metabolites, which serve different purposes. So no, a probiotic formula intended to aid in sleep is not interchangeable with one intended to aid in immune health.
• DNA verification: “DNA identification is the only way to ensure that you’re getting the most effective probiotic strains,” Sugarek MacDonald maintains. “Not all strains are created equal.” She notes that Pasteur Institute is dedicated to the study of microorganisms and the characterization of the DNA sequence of each strain.
• Symbiotic probiotic strains: Probiotic strains can kill off other strains, Sugarek MacDonald notes, so not only is it important for the individual strains to be scientifically proven—the whole formula has to be tested to ensure that the strains inside are compatible with each other.
• Made to survive: Probiotics have to survive manufacturing and stomach acids. The manufacturer you buy from should be transparent about what methods were used to keep those probiotics viable.

Sid Shastri, product development manager at Kaneka North America LLC, based in Pasadena, TX, adds to this list the qualifier actual trial dosage. “It is not uncommon to find that a commercial probiotic product does not line up exactly with the amount and format of the strain that was utilized in the clinical trial,” he contends.

And when it comes to survival, Leah Nicolo, director of marketing at Enviromedica, Austin, TX, contends that spore-based organisms (SBO) are best: “Non-SBO probiotic supplements are made from fragile, lactic acid-based organisms that are killed off by acid, heat, and light. SBOs are inherently resilient, protected by a natural seed-like structure so they survive their journey from manufacturing to store shelves to the gut.”

John Deaton, VP of science & technology at Deerland Probiotics & Enzymes, notes that these spore-forming bacteria have a variety of benefits beyond their resilience. “B. subtilis and its relatives can persist in the GI tract, increase its numbers and then re-sporulate; block bacterial pathogens from colonizing, thereby maintaining a healthy probiotic community; communicate with intestinal cells to maintain healthy gut barrier function; and increase immune reaction of intestinal cells.”

And if you’re looking for a genome sequenced strain, DE111 B. subtilis is one. How can you be sure? “Through Deerland’s partnership with Cornell University,” Deaton says, “DE111® B. subtilis has been fully sequenced for safety and has been uploaded to GenBank, the National Institutes of Health genetic sequence database.” You can ask for proof, he says, that the strain has been uploaded to GenBank as one method of verification.

It’s also worth noting that, according to Wasserman, probiotics are unique ingredients on a strain level. “Each new strain needs to be individually declared GRAS,” he says. This makes sense on a scientific level, according to Shastri. “Strains refer to individuals of a given species that have specific traits that set them apart from other individuals from the same species,” he says. He uses Lactobacillus plantarum as an example: “We at Kaneka selected three very specific strains of L. plantarum that had the most potent effects on lipid metabolism and bile salt hydrolysis activity, which we use in Floradapt Cardio. Other strains don’t have the same lipid-modifying effects.”

Deaton concurs, and notes that this is another reason why genome-sequencing is so important. “It unlocks what each gene in the DNA genome does, how the genes interact and how the various parts of the genome are coordinated. By mapping out and revealing the DNA contained within the bacteria, we can identify any bad genes or antibiotic-resistant genes it may contain. The former may exert health issues while the latter is capable of being transferred between bacteria in the gut.”

This is how products with proprietary blends come to be: For instance, the Kyo-Dophilus Probiotics from Wakunaga are made with what the company calls “The Friendly Trio”: Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and B. longum MM-2. The trio has been shown to support digestion, allergy symptom, and a healthy microbiome—but other strains, even from the same genus and species, may not do the same.

None of this should be a problem if you’re ordering from a reputable manufacturer, but it is worth pointing out to any customers considering ordering from Amazon, where products aren’t necessarily vetted as stringently.

You also may want to consider talking to older customers about what probiotics can do for them: Andreas Koch, marketing director at Pure Essence, says that as we age, our microbiome naturally changes. “Research shows that aging, along with antibiotics, oral contraceptives, many prescription drugs, chlorinated water, and more can deplete the probiotic cultures that inhabit the human gut. Those 40 years or older typically have greater depletion than younger people.” He adds that a good balance would be around 53% Bifidobacterium and 47% Lactobacillus.

Speaking of antibiotics, they’re being prescribed more and more often, and can deplete the microbiome. Probiotics like Pure Essence’s Restore formula can come in handy here, too–and not just after the fact: “Some may ask if antibiotics negate the value of using probiotics,” Cochern says. “Undoubtedly, they diminish the value, but studies have shown that even a transient presence of probiotic supplementation provides benefits.”

Moving beyond digestive health, probiotics are great for immune support—you already know this, but it’s worth repeating. “No matter what the specific disease condition is,” says Greg Cooper, director of business & product development with Jackson GI Medical/Prebiotin, Camp Hill, PA, “ultimately, the solution to illness brings us back to gut bacteria. As much as 80% of our entire immune system is in our gut! With the right balance of bacteria,” he notes, “we are protected from pathogens and illness throughout our system, whether the illness is asthma, bronchitis, or an ear ache.” Given a poor diet, the microbiota, Cooper says, “are no longer resilient or diverse enough to stimulate an effective immune response,” leading to gut dysbiosis and an increase in all disease conditions. Just as the immune system begins in the gut, your customers may find it useful to start their journey to immune health in the probiotics section.

Probiotics don’t end their usefulness there. Start thinking skin. Belle & Bella has a Skin Therapy product based on clinical studies—the probiotic strains and the number of CFUs in the product are clinically proven. “Our gut and our skin are the two largest organs of detoxification in our body,” says Alan Cheung, executive director at Belle+Bella, Lexington, MA. “If our gut is out of balance, it will manifest on our skin. This is known as the skin-gut axis.” The skin-gut axis was first proposed around 80 years ago, by John H. Stokes and Donald M. Pillsbury (3). It has been thoroughly validated since then: a 2008 study involving 13,215 Han adolescents found that gastrointestinal dysfunction was “an important risk factor for diseases of the sebaceous glands, correlated with their occurrence and development” (4). Customers looking for help with skincare woes might want to start with a probiotic.

There’s also oral health. We know about the bad bacteria that makes up plaque and creates bad breath; Why not think about good bacteria? And not the same good bacteria that resides in the gut, either: According to Shastri, “Bacteria which are good colonizers of the intestine can be poor colonizers in the oral cavity, and vice versa.” Kaneka provides Floradapt in a gum health formula, comprised of three clinically supported symbiotic strains. Shastri notes that, unlike digestive probiotics, probiotics intended for the oral microbiome “have to be released in the mouth and stay there, as bacterial translocation from the gut to the mouth is null.” Oral probiotics tend, therefore, to be chewable instead of swallowable: chewing gum or lozenges instead of capsules or soft gels.

Stratum Nutrition supplies Streptococcus salivarius K12, a good oral bacteria, as BLIS K12 to formulators, which can support oral health, as well as ear, nose, and throat health.

And while we tend to think of probiotics as an inside-out kind of thing, there’s nothing stopping them from being just an out kind of thing. Desert Essence is now selling a probiotic hand sanitizer—not postbiotic, probiotic. Christine Allmer, marketing director at Desert Essence, Hauppauge, NY, notes, “Good bacteria exist on our skin without damaging it and represent a system of protection that helps keep our skin in balance. There are communities of microorganisms on the skin, which—when balanced—help prevent the spread of germs.” Thus, she says, it makes sense to add these microbes to hand sanitizer: “Traditional hand sanitizers will kill most common harmful germs; however, in the process, they also kill the good bacteria which contributes to a microbiome imbalance, creating unhealthy, unbalanced skin.” The kefir probiotic used in their hand sanitizer, she says, helps support a healthy microbiome—and it’s food-safe, in case of oral contact.

When talking about probiotics with a customer, it’s useful to remind them that we didn’t always have supplements. A customer looking for a specific benefit might find supplements more useful, but functional foods can serve the same purpose: Feel Better Pops are made with whole fruits and GanedenBC30, for a summertime probiotic treat. For those just looking for a general boost, though, they can go through the grocery section. Sauerkraut and kimchi might not come with the precise strain and CFU count on the package, but they’re a good way to boost probiotic intake, as is yogurt. For those customers who have trouble with yogurt—the sugar count, the type of milk used—suggest homemade.

Homemade yogurt has several benefits. Cheung notes that it gives the maker total control: “The ingredients in yogurt should be “milk and cultures.” When you make your own, you can choose the type of milk you like, you can add fresh fruits, honey, or granola, and you can leave out the thickeners, preservatives, and artificial anything.” Because it’s fresh, too, it can have a higher probiotic count than ready-to-eat yogurt. An extra benefit includes sustainability: Homemade yogurt goes into a reusable container, reducing personal use of single-use plastic cups. Milk might not be the first thing your customers consider when they’re looking for more probiotics, but signs next to different types of milk suggesting that coconut milk would make sweeter yogurt or that almond milk brings a nutty flavor can plant that seed. Don’t worry about losing ready-to-eat yogurt sales—there will always be people without the time or inclination to go homemade.

Prebiotics
Ingesting good bacteria (or applying it!) is only half the battle: Bacteria need to eat. “A healthy microbiome,” says Ross Pelton, scientific director with Essential Formulas, Irving, TX, “requires two things: Probiotic bacteria and a diverse range of fiber-rich foods in the diet.” Anke Sentko, VP of regulatory affairs and nutrition communication at BENEO, Parsippany, NJ, specifies: “Prebiotics support digestive health and wellbeing by supporting good bacteria. They are food components that reach the large intestine and function there as preferred feed for a few specific beneficial microorganisms.”

Prebiotics are most commonly oligosaccharides—FOS, GOS, XOS, and inulin—but the definition also encompasses conjugated linoleic acid and polyunsaturated fatty acid, although they’re not as heavily researched in terms of prebiotic activity as oligosaccharides (5). And aside from that? “There are no other scientifically established prebiotics at this point in time,” Sentko says, “only potential candidates.”

Lauren Clardy, VP of branded ingredients at AIDP, City of Industry, CA, notes that this does, in fact, mean that no, fibers in fruits and vegetables do not necessarily have prebiotic benefits. “Prebiotics selectively grow the beneficial bacteria,” she emphasizes. Wasserman mentions that the definition also includes non-fibers. Prebiotic is not interchangeable with fiber.

Furthermore, while “beneficial bacteria” is usually considered to be species in the Bifidobacterium and Lactobacillus genera, those certainly are not the only ones: Just Thrive notes on their website that beneficial bacteria includes species like Akkermansia muciniphila, which promotes a healthy metabolism and fat loss, and Faecalibacterium prausnitzii, which can increase the production of butyrate (a short-chain fatty acid—check out the Postbiotic section for more information on that) and may support liver health.

The best source for inulin, XOS (xylooligosaccharides) and FOS (fructooligosaccharides) is chicory root, but they can be found in onions and garlic, too, among other foods. Sentko says chicory root fiber—the richest source of prebiotics; dried, it’s comprised of upwards of 67% inulin—has been demonstrated to increase Bifidobacteria in more than 30 human intervention studies, covering various ethnic groups, every age, different durations, and different intake levels. GOS (galactooligosaccharides) is found most in Jerusalem artichokes, and in smaller quantities in beans and lentils—but even in Jerusalem artichokes, it’s only 7.5% of the food’s weight.

It’s worth it to keep an eye on what falls into the prebiotic category. Just because oligosaccharides and the two acids are the only prebiotics we know of at the moment doesn’t mean they’ll always be the only ones. For instance: green banana flour is generally considered a prebiotic. It’s rich in resistant starch, which boosts digestive health and the microbiome in general. AIDP is now the official distributor for NuBana, so you can keep an eye out for green banana flour-fortified food and beverages to sell for general gut health.

Enviromedica is looking for another prebiotic in riboflavin. According to Nicolo, “Riboflavin has been studied as a possible prebiotic whereby it mediates oxygen stress in the gut, allowing for successful proliferation of beneficial bacteria. However, it is a nutrient primarily absorbed in the small intestine, never making it to the lower intestine, where it can do the aforementioned work. Terraflora allows for riboflavin to be produced at the site of absorption.” Is it necessarily a prebiotic? The International Scientific Association for Probiotics and Prebiotics (ISAPP) doesn’t currently include it, but one day it might.

Another example of a possible prebiotic comes from Artemis International, Inc., Fort Wayne, IN. Melanie Bush, director of berry science at Artemis, notes that polyphenols—flavonoids high in antioxidants, one of which is the well-known compound resveratrol—have been shown in several studies to have the “ability to positively modulate the composition of the intestinal microbiota.” One 2012 study she cites showed that anthocyanins—a type of polyphenol that serves as the color pigment in berries—“have a prebiotic-like effect by increasing the population of beneficial gut bacteria like Bifidobacterium spp. and Clostridium coccoides, while inhibiting the growth of more detrimental bacteria like Bacteroides spp. and Clostridium histolyticum.”

That being said, the words “prebiotic-like” are key. Bush notes that “There are two schools of thought in the polyphenol-gut connection. The first is that the active compounds in flavonoid-rich berries are behaving similar to a prebiotic. The second mechanism of action involves the bacteria of the gut breaking down the larger flavonoid compounds in berries into more bioavailable metabolites that directly impact the related inflammatory pathways in the body.” Again, not what you’d recommend as a prebiotic, specifically—but a good recommendation for general gut health, and a good reason to keep an eye on the prebiotic category.

Prebiotics are a great choice for people looking to kick their digestive health up a notch. Clardy says that “Globally, many people suffer from a variety of digestive disorders such as bloating, constipation, acid reflux, and many others. Prebiotics have an advantage over probiotics and enzymes, in that they can address the whole spectrum of digestive health conditions.” The company’s PreticX, for instance, “selectively feeds beneficial bacteria, without feeding the bad bacteria, causing a favorable alteration in the gut microbiome.” Clardy notes that it has been shown to boost levels of Bifidobacteria and Bacteroidetes fragilis, two beneficial strains, and to decrease levels of non-beneficial bacteria, leading to a gut-wide reconditioning (6). Feeding good bacteria the food they need also means that they can properly produce postbiotics, responsible for many of the benefits received from probiotics.

Last but not least, if you happen to sell a food product fortified with prebiotics—or something like Uplift Food’s Daily Uplifter, a powdered supplement—you can tell your customers that prebiotics don’t affect the taste of food. In fact, according to Sentko, inulin and FOS can maintain or actually improve taste and texture. FOS, she says, “can be used in conjunction with high intensity sweeteners to help mask undesired off-tastes.” Inulin contributes to a creamy mouthfeel. And, of course, there’s an increase in dietary fiber, which, as Pelton notes, is the number one nutritional deficiency in America, making supplements or fortified foods a painless way of getting an important dietary component.

Synbiotics
“Synbiotics” refers to any supplement containing both a pre- and probiotic. It’s a good idea to take these: “Prebiotics function complimentary to, and possibly synergistically with, probiotics,” Sugarek MacDonald explains. “Preliminary data suggests that combinations of pre-and probiotics can provide a positive impact on gastrointestinal health above and beyond what each individual component can provide separately.” And what the two can provide, she says, is a necessary intervention: “Preliminary evidence is emerging that pre- and probiotics may be useful in conditions including inflammatory bowel disease, allergies, poor mineral absorption, and vaginal and urinary tract infections.”

More science is necessary, Sugarek MacDonald says, but it looks promising. Most of Bluebonnet’s probiotic products are synbiotics, containing FOS; Dr. Axe sells Gut Formula, another synbiotic. Synbiotics don’t yet have much science behind them, but you can probably hold your breath on this one—it won’t be long before they do.

Postbiotics
The definition of postbiotics is in flux. Wasserman notes that it can refer to dead and decomposing probiotics, but it often refers to the metabolic byproducts of beneficial bacteria. Fermented foods generally already contain these byproducts; otherwise, they’re created when probiotics digest prebiotics. Generally, a HABA product that says it’s “probiotic” or “probiotic-derived” actually contains postbiotics—of either definition—unless it says otherwise. When purchasing these kinds of products, request clarification from the manufacturer regarding the claim.

According to an infographic from Essential Formulas (7), there are five general types of postbiotics, as per the metabolic byproduct definition:

• Nutrients—B vitamins, vitamin K, various amino acids
• Antimicrobial peptides—Natural antibiotics that suppress the growth of bad bacteria
• Short chain fatty acids (SCFAs)—Optimize the pH balance in the GI tract and suppress pathogens
• Carbohydrate-active enzymes—Help probiotics digest fibers
• Hydrogen peroxide—Suppresses the growth of Candida and other yeasts

Different postbiotics are created by different bacteria, making diversity crucial. “Numerous studies have demonstrated that prebiotic fiber like Prebiotin is fermented in the colon,” says Cooper, “and increases the activity of bacteria that produce SCFAs, especially acetate, propionate, and butyrate. An increase of SCFA is associated with reduced disease risk.” Backing Cooper up, researchers in Brazil published findings in April listing sodium butyrate as a bioactive compound that affects gene expression—including genes related to the development of certain cancers (8).

Postbiotics do, of course, have uses not related to cancer. “Butyrate also helps to regulate the body’s energy homeostasis, helps to maintain the regulation of food intake, and energy expenditure,” Cooper says. In other words: SCFAs, particularly butyrate, help regulate energy. “When you are balanced, you process calories efficiently, helping your body to work at peak efficiency. Eat a diet with minimal prebiotic fiber, and you will have fewer SCFAs. You will eventually feel less energetic, and won’t be able to function as effectively.” Are your customers looking for help keeping their energy up during the day? Point them towards your digestive health section.

How about immune health? Bush cites a 2017 study that found that feeding Clostridium orbiscindens flavonoids caused it to produce desaminotyrosine (DAT), which in turn strengthened immunity. “The presence of DAT actually helped to protect against damage from influenza through augmentation of Type 1 Interferon signaling and a reduction of lung damage,” Bush says. “Additionally, treatment with antibiotics can worsen influenza because the resulting loss of the microbiota interrupts the production of bioactive metabolites like DAT.” Again—point immune health hunters towards your digestive health section.

And, of course, postbiotics have a day job: Just keeping the microbiome healthy. According to Essential Formulas’ website, postbiotics are what let us thrive: “A robust, naturally diverse microbiome will make all the postbiotics a body needs. However, when fewer families of bacteria are on board, the variety of postbiotics is also reduced—and our vitality suffers. Eating fermented natural foods supports our intestinal bacteria and delivers postbiotics that they have made during fermentation” (9).

People looking for a specific benefit might want to look into specific strains. For instance, Just Thrive’s probiotic contains Bacillus indicus HU36, which produces antioxidants right in the digestive system. Enviromedica’s Terraflora supplement produces riboflavin, right where the gut can benefit from it the most.

So while you’re talking up pre- and probiotics, don’t forget to educate your customers on the oft-forgot heroes: the variety of vitamins, minerals, enzymes, neurotransmitters, immune-signaling compounds, and SCFAs that probiotics produce after fermenting prebiotics.

It’s possible to buy supplements with postbiotics included, too, for an immediate health boost. Dr. Ohhira’s sells a probiotic supplement that includes a postbiotic concentrate. Audrey Ross, senior national educator at Country Life Vitamins, Hauppage, NY, notes that Country Life’s CognitiveBalance prebiotic supplement contains a whole food fermentate: prebiotics and postbiotics, which, along with the Cognivia and NeuroFactor in the supplement, boosts the brain starting in the gut.

Psychobiotics
Psychobiotics are defined as probiotics and prebiotics which, when ingested, confer mental health benefits through interactions with commensal gut bacteria. The term was defined as such in a 2016 review by Amar Sarkar et al.; Previously, the definition did not include prebiotics, according to a 2013 study by TG Dinan, C. Stanton, and JF Cryan (2, 10). This is a new concept, and it’s not set in stone—Sarkar et al. suggest that the
definition be expanded to include “any exogenous influence whose effect on the brain is bacterially-mediated,” or any outside factor that works on the brain through the gut.

Ross agrees that psychobiotics comprise more than just pre- and probiotics. “Vitamins, minerals, amino acids, polyphenols, and other metabolites all play a role in keeping a healthy gut microbiome. There are trillions of microbes in the gut that are responsible for keeping the bad bacteria at bay as well as making numerous chemicals that affect how the brain works. These signals get scrambled whenever there is an imbalance in the gut microbiome.” So yes—vitamins and minerals and more may play a role in keeping the brain healthy, but they do so by keeping the gut healthy. By, in other words, being psychobiotics.

While the term and the concept are new, the gut-brain axis isn’t. Jarrow makes a product containing probiotics and GABA to support the gut-brain axis; Natural Factors makes a Calm Biotic. The fact that scientists are still codifying what it means to be a psychobiotic doesn’t mean we’re only now getting psychobiotics on the market—it just means that products geared towards the concept are going to find their way onto your shelves.

Probiotic Science is On the Rise
This isn’t the last you’ll hear about the microbiome; We’re not even in the home stretch. On the most basic level, probiotics will keep being necessary—a report from Transparency Market Research (TMR) found that the probiotics market will expand at 8.3% CAGR during 2018-2026, anticipating that it’ll be valued at $12,753.4 million by the end of 2026 (11). Understanding of how antibiotics can affect the microbiome, TMR reports, will drive that growth. “Probiotics is a big category, and there’s a lot of excitement around it,” says Wasserman. “It’s second only to CBD in terms of consumer interest.”

Beyond that, scientists haven’t yet found a limit to what the microbiome can do and how we can manipulate it, and they’re not done searching. Bush mentioned that one area she’s excited about is the combination of synbiotics with antioxidants: “Preliminary studies suggest that the incorporation of antioxidant compounds along with a probiotic could have cumulative benefits. For example, to investigate the functional outcomes of incorporating antioxidant compounds into the human gut, Roberts et al. (2016) measured the impact of a prebiotic-probiotic-antioxidant blend on endotoxin levels in humans pre- and post-triathlon. The treatment blend reduced endotoxin levels both pre- and post-race, compared to the synbiotic alone.”

Nicolo is excited about other combinations. “EnergyBalance contains elevATP to support the production of ATP. The combination of unique ingredients in SleepBalance helps the microbiome facilitate the body’s ability to produce neurotransmitters and get them to where they need to go. It’s about balance and the ability for clear signals to be sent between the gut and the brain.”

Applications for probiotics will continue to evolve, too. Deerland suggests to its customers the use of DE111 in foods: “The idea is to create a desirable functional food,” Deaton says, “To take what was once a “no no” food and use its nutritive value to blend with probiotics, creating a guilt-free, nutritious treat.” Deerland uses chocolate as an ideal food to blend probiotics with. Why? As Deaton explains: “The bacteria that thrive toward the end of the digestive tract—like B. subtilis—ferment both the antioxidants and fiber in the cocoa. Combining probiotics like DE111 with chocolate multiplies the benefits the chocolate provides, such as supporting healthy blood flow.” Pills and capsules are all well and good—but chocolate might be where probiotics go next.

Keep an eye on this market, and on the science that’s expanding its reach. Make good use of helpful resources like the Global Prebiotic Association and the International Probiotics Association, there to help raise awareness and educate stakeholders. And keep an eye on WholeFoods—we’re keeping up with this, as we have been since the beginning. WF

REFERENCES

1. J.E. Aguilar-Toalá et al, “Postbiotics: An evolving term within the functional foods field,” Trends in Food Science & Technology, 75, 105-114(2018). https://www.sciencedirect.com/science/article/abs/pii/S0924224417302765
2. Amar Sarkar et al., “Psychobiotics and the Manipulation of Bacteria-Gut-Brain Signals,” Trends in Neurosciences, 39(11), 763-781(2016). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5102282/
3. Whitney P. Bowe and Alan C. Logan, “Acne vulgaris, probiotics and the gut-brain-skin axis—back to the future?” Gut Pathogens, 3(1), 2011. https://gutpathogens.biomedcentral.com/articles/10.1186/1757-4749-3-1
4. H. Zhang et al., “Risk factors for sebaceous gland diseases and their relationship to gastrointestinal dysfunction in Han adolescents,” The Journal of Dermatology, 35(9), 555-561(2008). https://www.ncbi.nlm.nih.gov/pubmed/18837699
5. Glenn R. Gibson et al, “Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics,” Nature Reviews Gastroenterology & Hepatology, 14, 491-502(2017). https://www.nature.com/articles/nrgastro.2017.75#ref4
6. Michael Crane, “Xylooligosaccharide Prebiotic Improves Gut Flora in Pre-Diabetic Subjects, Study Suggests,” Nutritional Outlook. Posted 1/30/16. Accessed 4/29/19. http://www.nutritionaloutlook.com/blood-sugar/xylooligosaccharide-prebiotic-improves-gut-flora-pre-diabetic-subjects-study-suggests
7. “Explaining Postbiotics,” EssentialFormulas.com. Infographic. Posted 4/2018. Accessed 4/29/2019. https://essentialformulas.com/wp-content/uploads/2018/04/Simple-Postbiotic-infogragh.pdf
8. WholeFoods Magazine Staff, “Study: Curcumin, Resveratrol Possible Anti-Cancer Compounds,” WholeFoodsMagazine.com. Posted 4/23/19. Accessed 4/29/19. https://wholefoodsmagazine.com/news/main-news/study-curcumin-resveratrol-possible-anti-cancer-compounds/
9. “What are Postbiotic Metabolites? The Unsung Heroes of Our Health,” EssentialFormulas.com. Accessed 4/29/19. https://essentialformulas.com/explaining-postbiotics/
10. T.G. Dinan, C. Stanton, J.F. Cryan, “Psychobiotics: a novel class of psychotropic,” Biological Psychiatry, 74(10), 720-726(2013). https://www.ncbi.nlm.nih.gov/pubmed/23759244
11. “Global Probiotics Market to Reach US$12,753.4 mn by 2026, Driven by Increasing Demand for Diet Supplements,” Transparency Market Research. Published 3/2019. Accessed 4/29/19. https://www.transparencymarketresearch.com/pressrelease/probiotics-market.htm
12. “Biofilm Bacteria,” MPKB.org. Last Modified 1/11/2019. Accessed 4/29/19. https://mpkb.org/home/pathogenesis/microbiota/biofilm
13. Meng-Xin Hu et al, “Probiotics Biofilm-Integrated Electrospun Nanofiber Membranes: A New Starter Culture for Fermented Milk Production,” Journal of Agricultural and Food Chemistry, 67(11) 3198-3208(2019). https://pubs.acs.org/stoken/presspac/presspac/full/10.1021/acs.jafc.8b05024