A new information super-highway is developing, yet it’s not driven by a tech company. New pathways are forming in the research and manufacturing of probiotics. More roads are exploring the gut-brain axis. As the specific mechanisms of action supporting probiotics’ digestive health attributes are uncovered, so is more information about the potential for probiotics to influence other aspects of well-being, such as regulating mood and behavior. Enter psychobiotics, a new segment of probiotics aimed at supporting the gut-brain axis.
Advances in probiotic research—healthy microorganisms that help balance the flora in the gut—suggest the microbiota found within could be sending healthy signals to the brain and, in turn, the brain is sending healthy signals back to the gut. Think of psychobiotics as a 24/7 transit system full of tiny micro-workers moving in tandem to create the right balance of health and mood.
The introduction of psychobiotics is a needed category boost. Looking at SPINS' proprietary data for pre-/probiotics, the segment shows an overall 6% decline across the supplements/remedies departments for the 52 weeks ending Sept. 8, 2019 across natural, specialty gourmet and conventional multi-outlet retailers. The slowdown can be linked to increased competition from other upstarts in the fermented category like kombucha and other refrigerated functional beverages that are stealing consumer dollars away from traditional delivery methods.
If you’ve ever had a fluttering in your belly or felt like you should just “go with your gut,” experts say it’s the second brain found in your gut sending a message. This message could be the missing link between mood and digestion.
This “second brain” is technically the enteric nervous system (ENS) at work. The ENS is two thin layers of millions of nerve cells lining the gastrointestinal (GI) tract from the throat to rectum. It controls intestinal movement, fluid transport, blood flow and nutrient handling.
“The bacteria in the large intestine communicate with human epithelial cells, which signal the brain,”1 said Tom Laaman, Ph.D., director of technical sales, Specialty Enzymes & Probiotics. “The brain’s responses to infectious bacteria in the gut are influenced by these signals and control the body’s immune response.”
Psychobiotics are probiotics that, when ingested, may offer mental health benefits through interactions with intestinal bacteria.
“The most interesting recent developments in research indicate that mental health issues including depression and anxiety are also affected by the microbiome,” Laaman said. “Probiotics have been shown to ameliorate both depression and anxiety and can even improve ADHD behavior.”2
For example, nervousness or anxiety often go together with stomach distress. And for severe cases of anxiety, physicians routinely prescribe a drug that can ease the symptoms. But it’s the positioning of all-natural multi-strain and multi-function probiotics for these mental disorders that has led to new terminology such as psychobiotics to cover these expanded health benefits.
Psychobiotics are relatively new, with just a few rodent studies and some small human trials to date.3 Yet, several products have been introduced that support these therapeutic benefits.
According to Tom Vierhile, vice president of strategic insights, North America, Innova Market Insights, 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, though from a small base, he said.
An April 2019 Innova Market Insights report on the U.S. brain/mood new supplement product market found it expanded at a compound annual growth rate (CAGR) of 6.5% from 2013 to 2018.Only the digestive/liver new product health category grew faster, expanding at a 7.1% CAGR over the same period, when looking at launch growth.
“Although digestive and immune health positionings are still the core focus for probiotic supplements, 5% of all new (supplement) launches in 2018 also included brain/mood health claims (up from 2% in 2013),” the report stated.
This, Vierhile said, is a sign that this gut-brain axis trend is beginning to gain traction, and it should make noise in the future.
The category could certainly gain more legitimacy now that Canada’s Natural and Non-prescription Health Products Directorate granted the first and only probiotic health claim focusing on the gut-brain axis to Lallemand Health Solutions. The available language for Probio’Stick® (a combination of Lactobacillus helveticus Rosell®-52 and Bifidobacterium longum Rosell®-175 in a stick format) now also includes, “Helps to moderate general feelings of anxiety,” and “Promotes a healthy mood balance.”
So, what will drive consumer interest in, and ultimately products that support, these two brains working to achieve wellness? Experts point to a globally aware and health-conscious consumer, better strain selection, product diversity and, of course, media influences.
Growing consumer awareness
Consumers are more aware of the importance of gut health on the entire mind and body’s well-being, so the market is there, said Sabinsa’s worldwide president, Shaheen Mahjeed.
In 2019, Kerry Group surveyed 2,100 health-conscious U.S. consumers as part of its Global Consumer Survey. From the internal company survey, Kerry found:
- 62% of respondents said they were aware of probiotics
- 33% had used probiotics in the last six months
Among American consumers who are aware of probiotics, 79% of respondents said the promotion of good digestive health is the most important health benefit they seek in a product.
“So, there’s no reason to think that growth won’t continue,” said John Quilter, vice president and general manager, Kerry. “None of the trends driving the popularity of probiotics are showing signs of abating.”
Ralf Jaeger, managing member, Increnovo, and senior scientific advisor to Ashland, agreed, saying probiotics offer consumers meaningful, bite-sized messages like “stronger defenses’’ or ‘‘better immunity.” These, he pointed out, are benefits consumers can relate to rather than complex ingredients. Ashland is the official North American distributor of probiotics produced by Probiotical S.p.A. in Italy.
“Those benefits can be felt and monitored by consumers during their daily bathroom routine,” Jaeger said.
Jaeger pointed out how the media can help impact consumer awareness, and thus widen the purchasing base. After Lactobacillus GG was introduced in the early 1990s, it took the company more than five years to get the acceptance of consumers by creating a health-promoting, good tasting product with a reasonable price, Jaeger said.
From there, he said the rest is history with scream queen Jamie Lee Curtis speaking openly on TV commercials about her regular bathroom trips. The commercials were a tipping point, as they moved probiotics into everyday conversation. It also gave way to showcasing new forms of probiotic products: functional foods and beverages.
Majeed contended the road to a healthy gut-brain axis is simple: Explain to consumers that they should start with and maintain a healthy gut microbiome. After all, he said, gut-brain axis health issues like irritable bowel syndrome (IBS) are hard to diagnose in the early stage, and medical practitioners often treat symptoms rather than underlying problem.
“The key is in using suitable strains that have well-established evidence for survival of probiotics in transit through the gut as well as clinical indications for health benefits in maintaining gut health,” Majeed said.
Emotional states might alter the normal intestinal microflora, causing small intestinal bacterial overgrowth (SIBO), increase intestinal permeability and contribute to systemic inflammation.4 SIBO is associated with depression and anxiety.5 Studies show the frequency of SIBO in patients with IBS is higher than that in a healthy population.6
Sabinsa’s patented Bacillus coagulans MTCC 5856 (LactoSpore) was part of a 90-day randomized, double-blind, placebo-controlled trial of 40 patients suffering from IBS and major depressive disorder (MDD).4 The trial resulted in notable improvements in levels of depression associated with IBS.
“This study can open a new treatment line for depression with respect to IBS, and related mood and anxiety problems,” said Majeed. However, brands must ensure they are following legal claims for the jurisdiction where their products sell.
Added Cristiana Piangiolino, Ph.D., market manager, Nutraceutical Roelmi HPC: “We have to consider the beneficial effect of probiotics not only from a strictly intestinal point of view, but [also] their capability to reach several body districts through different direct or indirect mechanisms.”
Piangiolo cited examples like the physical migration to proximal sites such as oral ingestion leading to vaginal colonization or by releasing post-biotic molecules with antimicrobial capacity, enhancing enzyme activity or boosting the body’s defense.
More research, like the ability to identify and confirm new specific strains that directly impact mood, will be a driving factor in category growth around gut-brain axis products.
“Research into the precise benefits individual strains impart, however, has allowed for condition-specific probiotic products to be developed and marketed, and that is what’s really energized the category,” said Sabinsa’s Majeed.
Quilter said the data will be key in meeting the needs of an “increasingly savvy audience.”
Highlighting Kerry survey results, he said “[Communicating research] is probably the single greatest challenge for the probiotics industry right now, especially when you consider that only 15% of people believe that nutrition and performance drinks deliver on their promised claims.”
The products that will make it to the end of the road, Quilter said, are “well-studied, branded probiotics, that easily convey a benefit-driven story that consumers can understand and trust. A strong branded functional ingredient should be backed by documented safety, efficacy and quality.”
DuPont is looking at probiotics to improve cognitive health, specifically stress relief, with its HOWARU® Calm. Mariah Saerndahl, global communications, dietary supplements, DuPont Nutrition & Biosciences said she believes the increased focus on microbiome research, and how the bacteria in the gut can affect the health of the body beyond digestive and immune functions (e.g., brain and weight management) will help sales tick upward.
“As this body of research grows, so does the demand for innovative probiotic products to support multiple areas of the body,” Saerndahl said.
New product and delivery innovation
Euromonitor International, in its October 2018 “Probiotic Supplements: Theories on Future Growth” report, said pill fatigue is another contributor to slow supplement category growth. The industry will need to get creative in how it delivers this new mental health benefit.
SPINS data highlighted pockets of growth—4.8% increase overall—in shelf-stable grocery items (e.g., pretzels, hot cereal, and baby and toddler food/snacks).
Functional food category growth led Sabinsa to have its LactoSpore® shelf stable probiotic self-affirmed GRAS (generally recognized as safe).
Similarly, Kerry’s GanedenBC30® (Bacillus coagulans GBI-30, 6086) is a spore-forming probiotic, making it more resistant to extremes of pH, heat, cold and pressure than vegetative probiotic cells, which allows for fortification of everyday foods and beverages.
New packaging technologies offer alternatives to standard capsules, leading to a wide range of delivery concepts:
- Twin-sticks or double-room sachets allow a consumer to combine probiotics with other traditionally non-compatible ingredients
- A probiotic breath spray might be used every day.
- Multiphasic vials, characterized by an absorption tube inside a cup containing probiotics to help reduce water activity and offer stability can be a one-shot solution for seniors and children.
‘Biotics’ choices expand wellness options
Several more “-biotics” are making their way into the mainstream lexicon for their role in driving more personalized nutritional benefits. A blend of pre- and probiotics, synbiotics, delivers both the beneficial microorganism and the substrate required by the probiotic to multiply inside human intestine.
Prebiotics can help ensure beneficial nutrients make it to the gut. They are non-digestible fiber that stimulate the growth of probiotics, so it arrives alive and intact. These supplements are said to be useful for people with conditions like IBS and diabetes. Earlier this year, Nutrition Business Journal data showed synbiotic supplement sales reached US$5.66 billion in 2017, representing 19%growth from 2016. Synbiotic supplements are projected to achieve $8.81 billion in sales by 2020.
Roelmi HPC’s “-biotics” research is focused on the gut-brain-skin axis. The company investigated the effect of its probiotics on reducing skin discomfort. Preliminary, unpublished clinical study results demonstrated that SynBalance® ProBeautyShield (Lactobacillus plantarum PBS067, Lactobacillus rhamnosus LRH020, Lactobacillus reuteri PBS072) probiotic complex can counteract atopic skin-related discomfort and positively impact quality of life. According to Roelhmi, this outcome holds promise of probiotics’ influence on skin health.
According to Jaeger, probiotics have also been identified for specific age groups (e.g., children, adults aged 40 and older, and seniors) and gender-specific issues (e.g., women's health).
“One additional area of innovation is to understand and use probiotics to improve the absorption of certain key nutrients in food or supplements, resulting in an overall improvement of corresponding benefits (e.g., improved amino acid absorption from protein, increasing selenium absorption, etc.),” Jaeger said.
Promoting the consumer benefits of psychobiotics has its challenges. Specialty Enzymes’ Laaman cautioned that more precise human clinical research needs to be done to fully support and drive home findings on improved mental health.
“High level research eventually will really pinpoint ideal microorganism combinations to achieve maximum health,” Laaman said. “The ultimate goal will be to take a person with no anxiety and depression issues, and naturally create an elevated level of calmness and hopefulness.”
Instead of the probiotic working to ameliorate a disorder that started in the brain, the gut-brain axis goes to fix a problem that started in the gut yet affected the brain. For example, he said antibiotics can cause emotional issues because of the disruption of the normal flora in the gut.7 Lamaan pointed to Specialty Enzymes’ B. clausii, a staple Bacilli with a strong resistance to antibiotics.8 He said it can help maintain healthy microflora even during antibiotic use. ProbioSEB CSC3 is a combination probiotic consisting of B. clausii, B. subtilis and B. coagulans.
All three of these spore formers, he said, are highly shelf stable and stable in the high-acid environment of the stomach. In fact, a recent unpublished human clinical trial conducted by Specialty Enzymes and Probiotics found that B. coagulans resulted in statistically significant lower levels of anxiety, Lamaan said.
Similarly, Piangiolino said several studies are ongoing or about to be published regarding the connection between intestinal dysbiosis and the onset of psychological distresses.
As the specific mechanisms of action supporting probiotics’ digestive health attributes are uncovered, so too is more information about the potential for probiotics to influence other aspects of well-being.
- Kaelberer M, Bohórquez D. “The now and then of gut-brain signaling.” Brain Res. 2018 Aug 15;1693(Pt B):192-196. DOI: 10.1016/j.brainres.2018.03.027.
- Dolan K et al. “Probiotics and Disease: A Comprehensive Summary-Part 1, Mental and Neurological Health.” Integr Med (Encinitas). 2016 Oct;15(5):46-58.
- Cheng L et al. “Psychobiotics in mental health, neurodegenerative and neurodevelopmental disorders. J Food Drug Anal. 2019 Jul;27(3):632-648. DOI: 10.1016/j.jfda.2019.01.002.
- Stokes J, Pillsbury D. “The effect on the skin of emotional and nervous states: I II. Theoretical and practical consideration of a gastro-intestinal mechanism.” Arch. Derm. Syphilol. 1930, 22: 962–993.
- Addolorato G et al. “State and trait anxiety and depression in patients affected by gastrointestinal diseases: psychometric evaluation of 1641 patients referred to an internal medicine outpatient setting.” Int J Clin Pract. 2008 Jul;62(7):1063-9. DOI: 10.1111/j.1742-1241.2008.01763.x.
- Vaillancourt, J. “Ending the war metaphor: the changing agenda for unraveling the host-microbe relationship. Regulating pre- and probiotics: A U.S. FDA perspective.” Institute of Medicine of the National Academies. National Academies Press; Washington, DC: 200 p. 229-237.
- Lurie I et al. “Antibiotic exposure and the risk for depression, anxiety, or psychosis: a nested case-control study.” J Clin Psychiatry. 2015 Nov;76(11):1522-8. DOI: 10.4088/JCP.15m09961.
- A. Abbrescia et al. “Antibiotic Sensitivity of Bacillus clausii Strains in Commercial Preparation.” Curr Med Chem. 2014 Dec; 1(2): 102–110. DOI: 10.2174/2212707002666150128195631