Probiotics Populate New Markets

Now that people are beginning to understand how good bacteria can contribute to good health, the demand for these live ingredients is rising. Probiotics have long been ingested either in yogurt or dietary supplements but, as has been the case when other popular ingredients hit the masses, customers want more choices. Sensitivities to certain aspects of processing, including temperature, have limited the types of finished products that could realistically deliver viable probiotic ingredients; however, emerging technologies are removing these obstacles and opening the market up for more interesting probiotic-containing goods.

To a 5-year old the world is filled with good guys and bad guys, and things are either one side or the other. In the world of bacteria, there are also good and bad strains, and the same simplicity of division applies. The more good guys there are and the fewer bad guys, the better the world isa theory that rings as true to a child as it does to probiotic science.

Its this simple message that has lured the public to learn about and consume more beneficial bacteria. Natural Marketing Institutes (NMI) 2008 Health and Wellness Trends Survey found awareness of the term probiotics in the general U.S. population skyrocketed in 2008 to 48 percent, up from 31 percent in 2007. This followed a 50-percent increase in 2007 from only 20 percent awareness in 2006.

Dannon capitalized early with its Activia yogurt, featuring a Bifidobacteria strain branded to reflect the ability of such probiotics to regulate digestion. Other companies launched similar yogurt products focused on probiotic content, and work was already underway to find some new applications for these probiotics beyond traditionally cultured foods.

Despite this push, consumers wont take just any probiotic-infused product. Euromonitor reported a cheese product featuring Krafts LiveActive probiotic ingredient drew little fanfare, because consumers shop for cheese in a special way, focusing on taste, texture, price and convenience, and they are not looking to pay extra for cheese with probiotics.

On the flip side, oral health products seem a good fit for probiotics. As any dentist worth his weight in white smiles will tell you, harmful bacteria are all over the mouth, gums and teeth, contributing to erosion of tooth enamel and periodontal disease. Among oral health products, gums and mints have enjoyed the largest growth, with functional gum climbing 10 percent between 2007 and 2008, for a total $5.7 billion market share.

In general, consumers tend to understand that harmful bacteria reside in the mouth, said Jeffrey Hillman, DMD, Ph.D., chief scientific officer for Oragenics, adding this awareness has been supported by products that claim to kill 99 percent of the germs that cause bad breath. What is now emerging in consumer education is the critical role good bacteria plays in maintaining and restoring optimal health.

Lactobacillus strains are effective against enamel-eroding bacteria, such as Streptococcus mutans , and many companies are already active in developing probiotic gums and mints with this family of probiotics. A sugar-free gum containing Lactobacillus reuteri (L. reuteri) is a recent offering from Swedish company BioGia. Also, Relief Mart offers Breath-Biotics, a mint containing a proprietary blend of L.reuteri, L. plantarum, L. rhamnosis and L.acidophilus that targets the bacteria that causes bad breath.

Nutraceutix Inc. also developed several probiotic breath mints designed for improved oral health, one of which is currently undergoing an academic medical center study. Tim Gamble, senior VP, sales and marketing, Nutraceutix, said the mints feature the companys LiveBac® processing, which improves shelf-life for probiotic tablets and caplets regardless of the particular strains involved, even at room temperature. They are expected to hit store shelves soon under national brands.

Similarly, Oragenics developed a mint (EvoraPlus®) featuring three probiotic strains designed to fight dental decay and bad breath. This breath mint contains the companys Probiora3 branded probiotic blendStreptococcus oralis (S. oralis KJ3), Streptococcus uberis (S. uberis KJ2) and Streptococcus rattus (S. rattus JH145).  

Hillman said probiotics for oral care is a new category and requires unique bacteria that are natural residents in healthy mouths. Although both sets of bacterial strains are classified as lactic acid bacteria, the bacteria in yogurt (and all gut probiotic products) are not residents of the oral cavity, and they won't hang around long in the mouth, he explained. Twenty-five years of data shown in studies prove that the specific organisms we patented as ProBiora3 have exerted a beneficial activity in the mouth.

Hillman also suggested a whitening effect, noting his companys trademarked strain of Streptococcus oralis binds to the surface of the teeth, crowding out harmful bacteria by competing for the same nutrients and surface spaces. In laboratory studies, the low-dose hydrogen peroxide produced by the S. oralis KJ3TM created a continuous whitening benefit that did not plateau over the duration of the study, he said, adding the ingredient also contains S. uberis KJ2 and S. rattus JH145.

Bacteria Everywhere

Altered microflora balance in the body, which is home to more than 10¹⁴ bacteria, is associated with health problems and diseases. This is more well-known relative to the digestion system, which hosts more than 400 different bacterial species in the intestines, including both good and bad bacteria competing for receptor sites. The prevailing theory is the good bugs can crowd out the bad bugs from these receptors, decreasing the negative effects harmful bacteria can have. In the digestive tract, probiotic ingestion has translated to positive effects on diarrhea, inflammatory bowel disease (IBD), lactose indigestion, irritable bowel syndrome (IBS), H. pylori colonization (linked to ulcers) and colon cancer.

However, bacteria are all over the body, including the mouth, skin, reproductive organs and various membranes. Thus besides digestive ailments, probiotic supplementation has been associated with allergies, autism, arthritis, and various liver and kidney diseases.

Another area of health not often considered digestive is immunity, which is linked to gut health. The intestinal epithelial layer contains certain lymphoid tissue called lamina propria, which interacts with gut microflora. Recent research has shown probiotics can have positive effects on cold and flu symptoms, allergic rhinitis and pollen allergies. While not definitive, the study being done on probiotics in this are of health has been drawing attention from product developers and formulators.

In fact, if a good offense needs a strong defense, a top growth segment for probiotics may be in immune defense. Research is showing that probiotics can positively modify immune response, said Michael Shahani, director of operations for Nebraska Cultures. This is the newest and most exciting area of probiotic research.

Mike Bush, VP business development at Ganeden Biotech, said immune health and probiotics have been linked together for a long time in other parts of the world, such as in Asia and Europe. Danones Actimel is a well-regarded functional immune beverage product worldwide, he said, noting the immune benefits outside the United States have been recognized for a long time. Now companies are working hard to promote benefits outside of standard digestion. This effort involves consumer education, which we are taking part in along with other probiotic companies and the International Probiotic Association (IPA).

Isabelle Champié, human nutrition brand manager for Institut Rosell-Lallemand, agreed this is a strong area of probiotic growth, especially with the flu epidemic threatening. She said, An increasing number of scientific publication and clinical evidence advocate the role of probiotics in the prevention of certain infections (e. g. ProbioKid from Institut-Rosell Lallem reduces the occurrence of common infectious diseases in children during winter by 25 percent).

The most recent research on probiotics and immune health includes HOWARU®, from Danisco, a combination of Lactobacillus acidophilus NCFM® and Bifidobacterium lactis Bi-07 . Children ages 3 to 5 receiving either L. acidophilus alone or in combination with the B. lactis twice daily had reduced their fever incidence by 53 percent and 72.7 percent, respectively, after six months of supplementation. Also, coughing was reduced by 41.4 percent and 62.1 percent, and runny noses were lessened by 28.2 percent and 58.5percent.¹

Lesser-known Bacillus coagulans GBI-30 (as GanedenBC30®, from Ganeden Biotech Inc.) may impact T-cell response to certain viral respiratory infections, according to recent research published in Postgraduate Medicine.² Researchers noted significantly increased T-cell production of TNF-alpha in response to exposure to both adenovirus and influenza A (H3N2 Texas strain).

In 2006, researchers at the North American Research Conference on Complementary and Integrative Medicine, Edmonton, reported on their study that showed probiotic tablets (Immunobiotix, from Nutraceutix Inc.) were shown to enhance phagocytosis by monocytes and neutrophils in a healthy adult human population.

Another recent trial found probiotics may stave off pneumonia. The study from the University Hospital in Lund, Sweden, found the bacterial strain Lactobacillus plantarum 299 is just as effective as antiseptics in protecting intubated, critically ill patients from ventilator-associated pneumonia (VAP), which occurs when harmful bacteria from the mouth, throat or breathing tube are inhaled into the lungs.³

The theory behind the immune effects of probiotics has focused on the stimulation of innate immune response and increasing pathogenic resistance, as evidenced by a slew of trials on many different strains of probiotics, especially Lactobacilli.^4,5,6,7

Additional Health Frontiers

While the industry awaits more definitive results on various probiotic strains and actions in immune health, there are newer frontiers being explored. Rosell reported other potential areas of health include inflammatory diseases, cholesterol reduction and certain anti-aging properties. Another exciting area already recognized by animal health experts, is stress management, with growing evidence on the interactions of the microbiota with the brain-gut axis, Champié said, noting her companys ProbioStick product was proven to be effective in reducing the gastrointestinal symptoms linked to stress in chronic stress sufferers.⁸ More recently, an animal study showed this probiotic preparation displayed an anxiolytic-like effect and was able to reduce signs of anxiety, she added. Such effect had never been previously described with probiotics and offers promises for new applications, including prevention of post-myocardial infarction depression.

"There is basic research underway on the role that probiotic bacteria play in the expression of different genesthis is exciting because it would involve many health conditions," said S.K. Dash, Ph.D., president of UAS Labs. "There are studies underway on the gut-brain connection and the possibility that probiotic bacteria may have a role to play; again, this may result in new health implications."

Ulrik R. Søndergaard, corporate communications at Chr. Hansen, noted two merging areas of health for probiotics are womens health, including the maintenance of vaginal microbiota; and infant health, specifically general microflora balance via infant formulas. Further, Chr. Hansen and the University of Copenhagen are collaborating on a groundbreaking weight management research project dubbed Prosat, developing scientifically documented probiotics that promote satiety and can be used in food and nutraceutical applications. The probiotics will target slightly overweight to standard weight individuals who want to maintain a healthy weight balance.

Overcoming Formulation Challenges

Looking through the research reports reveals a mixture of results on health, but the positive actions of probiotics are tied to specific strains at specific doses. Thus, the primary goal with any probiotic product is to deliver the right bacteria in ideal numbers to the right place in the body. It may seem a simple goal, but these beneficial microbes face a number of challenges that can destroy and disarm them. Foremost among these challengers is heat, which can have an adverse effect on any probiotic. For this reason most early probiotic products were refrigerated, including dairy products.

On its journey to absorption into the consumers body, a probiotic ingredient must face adverse conditions in handling, storage and processing; once the finished product is made, there are shelf-life issues followed by the harsh environment of the stomach (acid). To help improve survival of the probiotic along this perilous journey, companies have developed various technologies that safeguard the beneficial bacteria from manufacturing through to absorption.

At its most basic, a probiotic supplement avoids any processing that involves harsh heat, oxygen or moisture, and is enteric-coated for safe passage through the stomach. However, this does not allow for innovative applications beyond simple refrigerated supplements. Several multi-layer and release technologies have improved delivery in these areas. Despite the popularity of capsules in the U.S. market, there is worldwide demand for tablets, so Chr. Hansen employed the Probio-tec matrix that protects the probiotic during passage through the stomach. The bacteria in these tablets are also protected during the production process. Chr. Hansen's Probio-Tec® strains have documented effect, documented stability, proven safety and multiple applications, Søndergaard confirmed. Documented stability means that we provide stability data from raw material to packed consumer product at relevant storage conditions. Additionally, we ensure adequate cell count correlating to clinical documentation.

BioBeads® from Natrol take a three-layer approach protecting and controlling probiotics at distinct stages, including shelf-life/storage, ingestion and release point in the intestines. The outermost layer of the bead ensures at least 18 months of shelf life, while the middle layer shields the ingredients from stomach acid, and the innermost layer breaks down in the intestines to release the product.

This is similar to the True Delivery Technology used in Enzymatic Therapys Pearls probiotic supplement. As the company explains it, the inner layer consists of a paste of probiotic bacteria suspended in a protective oil suspension; the middle layer protects from air, moisture and heat; and the outer layer is the patented gelatin pearl that protects the entire product from stomach acid. It only dissolves in the alkaline confines of the small intestine. As a result, the company touts the product is stable for up to 18 months without the need for refrigeration.

Another multilayer approach was taken by Nutraceutix, which employs two complementary technologies to ensure longer shelf life and controlled release. Its BIO-tract® technology features a unique reaction; when the product comes into contact with stomach fluids, it forms a layer that protects the ingredients from gastric acid then releases the ingredients in the intestines over a period of time controlled by customization of the design. For probiotic ingredients, this technology can be paired with the companys Live Bac® technology, which it designed to help manufacturers meet label claim even at their products expiration date. The company said this patented tableting process ensures the probiotic ingredients are far less susceptible to harsh environmental factors than normal probiotics. "In the case of safe, natural traditional probiotics, shelf-life is a function of significant manufacturing expertise and specialized processing that only a few contract manufacturers and private label companies can claim to possess," Gamble said.

Most of these technologies are tailored and ideal for use in making finished supplement products, but some other technologies are helping probiotics make inroads to functional foods and beverages.

Lallemand offers a patented microencapsulation technology specially developed to improve probiotics survival in stressful conditions (gastric acidity, pressure, high temperature, etc.). Called Probiocap, this technological platform has contributed to innovative food supplements formatssuch as dietary supplements in stick format)but also food applications have been made possible, such as the first probiotic chocolate launched in Europe with Barry Callebaut, which is now also sold in health foods stores in America. Probiocap enables manufacturers to apply probiotic s in various food matrixes, even those which require long shelf life at room or chilled temperature, while retaining good viability, said James Kopp, Sr., vice president of Lallemand Nutritional Food Ingredients, who noted cereals bars, cereals, biscuits and diet meal replacements are additional ideal food applications.

Also aiding probiotics infiltration of the food market is a unique and inherent biological defense central to GanedenBC30. This is a gram-positive, spore-forming bacterium that, once germinated, produces L+ lactic acid, supporting good bacteria in the gut. As a spore-forming bacterium, the bacterial cell inside is a hardened structure, or spore, similar to a seed. The company explained this spore protects the cells genetic material from numerous environmental threats, including the heat and pressure of manufacturing processes and the acid and bile it is exposed to in the stomach. After reaching the safety of the small intestine, the spore germinates and produces new vegetative cells or good bacteria. This self-preserving probiotic is self-affirmed GRAS (generally recognized as safe) for use in foods and beverages requires no refrigeration and can have up to a two-year shelf life, according to Ganeden.

Weve been able to do things like hot soup, Bush said. We are in the process of working with a company that is launching a probiotic hot tea. Heat and probiotics dont normally get along, so for us its opened up the market.

Bush further noted the ability to ferment this probiotic and use its metabolites made topical, personal care applications possible. This is one of the first technologies we came out with, he said. It allows us to use the supernatant of our probiotic, the extracellular material that is produced by probiotic during a fermentation process that has some interesting antifungal and antiviral properties.

Still, this biological technology is inherent and special to this particular Bacillus strain. As Shahani pointed out, most probiotics still struggle in baked products, food bars or other food items that are extruded hot and under pressure, unrefrigerated drinks, hot drinks or hot food. Even Bush conceded there are still products with extreme processing that are too harsh for probiotic stability and survivability. There are other product ideas where weve seen challenges, but were able to work internally or with great industry partners to come up with a solution to what appeared to be unsolvable manufacturing issues, Bush said, noting a new venture with a partner on a thin strip product that dissolves quickly in the mouth. Its really hard to get probiotic into those things and keep them stable; its a pretty brutal cooking process.

Shahani added some other recent innovations helping various probiotics reach new applications include processing at lower temperatures, processing in a dry environment, and stabilization techniques that can help the bacteria survive under adverse conditions.

Despite some of the inroads probiotics have made in the area of functional food, Bruno Delattre, business manager Lal Foods, reiterated the importance of well-made raw materials being used in these delivery technologies. Most of all, we must keep in mind that the intrinsic properties of the selected probiotic strains, as well as every step of the production and lyophilization process, are key to probiotic stability and survival, he said. By constantly optimizing the lyophilization and formulation of our freeze-dried probiotic strains, we are able to develop various some specific food applications such as ice creams, fresh fruit juices and fresh vegetables applications

"Much of the strength of a probiotic starts with the strain of the organismsome strains are more resistant to heat, moisture, oxygen, acid and bile than othersthe L. acidophilus DDS-1 strain is particularly tough," Dash said, who noted UAS Labs uses stabilization technology to keep the organisms viable in different systems. He added a low water-activity environment can help to extend shelf life, as can flushing packages with nitrogen to keep out oxygen, and adding probiotic post-heat and pressure stages to limit the effects of temperature. 

Combination Trends

The differing opinions about single- versus multiple-strain formulas will persist until research decides the debate one way or another. However, one combination trend that is seeing convincing results is the pairing of probiotics with probiotics. Also called synbiotics, these combinations are based on the mechanism of probiotics feeding on prebiotics for enhanced survivability.

One such pair from Danone, a combination of galacto- and fructo-oligosaccharides (as Immunofortis®) and Bifidobacterium breve M-16V, was found to inhibit protein-induced allergic response in an animal study.⁹ The researchers noted the sensitization used in the study mimics the human route of sensitization.

Promising research, new delivery technologies and educational marketing are the primary drivers of this rising wave of innovation in probiotic applications. In the end the important goal is to get consumers to take their probiotics every day, whether in a tried-and-true supplement form or a clever new functional food or beverage. As long as they get the right amount of the specific strain proven to have a specific health effect, all in a protective and stable delivery form, formulators will have met their goal.

References on the next page...

"Probiotics Populate New Markets" References

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3. Klarin B et al. Use of the probiotic Lactobacillus plantarum 299 to reduce pathogenic bacteria in the oropharynx of intubated patients: a randomised controlled open pilot study. Crit Care. 2008;12(6):R136.

 4. Ramakrishna BS. Probiotic-induced changes in the intestinal epithelium: implications in gastrointestinal disease. Trop Gastroenterol. 2009 Apr-Jun;30(2):76-85.

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