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The Proliferation of Probiotics

Probiotics Probiotics

Funny how obscure terms sometimes take root and bloom in the consciousness of the masses. Take probiotics for example. It’s not an understatement to assert that only a decade ago, not many consumers were aware of the word, much less wanting to use them. Oh, and not many probiotics products were readily available.

Now, if a retailer was so inclined, it could have a probiotics department full of supplements, foods, beverages and now, even personal/body care. According to Colorado-based Sterling-Rice Group’s Natural Nine 2017 Natural Food Megatrend, “Probiotics may become the next megatrend. Consumers are increasingly aware of the correlation between digestive and overall health, and as new science drives shelf-stable snacking innovations and supports products claims, the U.S. probiotics segment is expected to continue to grow at double-digit rates annually.”

In 2015, according to data supplied by Sterling-Rice Group, the global market for probiotic products reached $41 billion, and this is expected to rise to $75 billion in 2025. One of the reasons for the growth, we can assuredly surmise is the continual launch of attractive products. As examples, provided by the Sterling-Rice Group:

• Farmhouse Culture Kraut Krisps featuring 1 billion CFUS per serving of Bacillus coagulans GBI-030 6086, available in five flavors.

• Wildbrine Sriracha contains 35 to 60 billion CFUs per bottle of this fermented and raw food, available in two flavors.

• Harmless Coconut Probiotics is a non-dairy coconut drink that offers 12.5 billion CFUs L. acidophilus, B. lactis, S. thermophilus, L. casei, L. bulgaricus, B. bifidum, L. rhamnosus, B. coagulans GBI-30 6086, and is available in four flavors.

• Also new by way of Italy is Innovia Probiotic Nectar Liquid Fiber probiotic microshot, with 8 billion CFUs of L. paracasei CNCM 1-1572 LP-DG\.

Ingredient suppliers that focus on manufacturing and researching probiotics are collectively accelerating their rate of clinical investigations that reveal and/or substantiate targeted use, as well as obtaining patents and more. It cannot be overstated that probiotics is a richly invigorated category that has yet to reach its full potential.

Chr. Hansen, headquartered in Denmark, has announced its partnership with Prota Therapeutics, an innovator of immunotherapies that focuses on food allergies, to investigate Chr. Hansen’s probiotic strain LGG, in a Phase III clinical trial to develop a treatment for peanut allergy, a potentially fatal allergy affecting a growing number of people. It is estimated that globally, up to 250 million people suffer from food allergies, an increase of 350 percent over the past 20 years. Specifically, approximately three million Americans have peanut allergy, the most common cause of anaphylaxis. The global market for peanut allergy therapeutics, according to the company, will reach approximately $10 billion by 2025.

The overall goal is to reprogram the immune system’s response to peanuts then develop a tolerance through a new form of immunotherapy treatment combining LGG (Lactobacillus rhamnosus) with targeted doses of proprietary formulations of peanut protein, developed by Prota Therapeutics.

Building upon earlier trials conducted at the Murdoch Children’s Research Institute, Prota Therapeutics is progressing toward a large-scale Phase III clinical trial, under a U.S. Investigational New Drug Application (IND) and this will also be one of the first Phase III clinical trials with a live microorganism.

According to Dr. Suzanne Lipe, CEO at Prota Therapeutics, the objective is to commercialize a medicinal product using a new pharmaceutical grade therapeutic dosage form for treating peanut allergy, and to explore indications for treating other food allergies. “An effective therapy to treat peanut allergies is now a realistic target. Together with our proprietary peanut protein formulation, we aim to progress this through to commercialization of a treatment for peanut allergies,” she said.

In a 2017 published study in the Journal of Probiotics & Health, researchers have found that consumption of Georgia-based Deerland Enzymes and Probiotics’ probiotic strain DE111 can improve occasional constipation and/or diarrhea in healthy individuals. In the 105-day study, 50 participants took either 1 billion CFU DE111 (B. subtilis) a day, or a placebo and their stools were scored based on the Bristol Stool Chart index. The results of the study showed a reduction of alternating constipation and diarrhea for the participants taking DE111 when compared to placebo. The proportion of normal stools (types 3 and 4) increased from 54 to 64 percent in the DE111 group, while the proportion of normal stools decreased from 56 to 48 percent in the placebo group. DE111 is a genome sequenced and clinically tested strain of Bacillus subtilis, a probiotic spore that supports digestive and immune health.

Athletes appear to be able to benefit from probiotics, as well, according to a 2016 study. Dr. Ralf Jäger, FISSN, CISSN; consultant, Pharmachem Laboratories Inc. a division of Ashland, New Jersey, explained that this showed that a combination of two encapsulated, anti-inflammatory probiotic strains, Bifidobacterium breve BR03 and Streptococcus thermophilus FP4, helped reduce the negative side effects of muscle-damaging exercise. Probiotic supplementation increased performance, reduced exercise-induced inflammation and increased range-of-motion, directly linking probiotic supplementation to sports specific benefits.

“Athletes are different than non-athletes when it comes to their gut microbiota, as studies have linked exercise and increased protein intake to a more diverse microbiome,” he said. Athletes have also more metabolically active bacteria, matching the activity level of the host. Athletes use sports nutrition primarily to improve performance or recovery. While probiotics have been linked to improved immune and gut health in athletes, until this study, no benefit of probiotic supplementation on performance had been reported.”

Patents are being granted for probiotics (and prebiotics), which underscores the rate of innovation in this dietary supplement category. Demonstrating that IBS (irritable bowel syndrome) remains a center target for probiotic research, Sabinsa Corporation’s (New Jersey) LactoSpore was granted a U.S. patent approving the use of Lactospore (Bacillus coagulans MTCC 5856) as a therapy for the management of IBS. Patent No. US9579352 states that when used as a dietary supplement along with regular treatment, LactoSpore can manage IBS symptoms of abdominal pain and distension, constipation and loose stools. A 2016 published human clinical trial suggested that Lactospore alleviated clinical symptoms of IBS in participants.

Deerland Enzymes and Probiotics received a notice of allowance for its U.S. patent application directed to prebiotic compositions comprising bacteriophages, namely Deerland’s branded prebiotic, PreforPro. “In our research and development, we’ve found that the prebiotic effect of bacteriophage is superior to traditional prebiotic ingredients,” said John Deaton, vice president of science and technology at Deerland. “It works at much smaller doses and much quicker.”

Despite all the strides in proving MOA and efficacy, probiotics need to be effective in delivery, notably in capsule form, which still dominates the market due to convenience and simplicity.

“Stability is a key issue for most probiotics,” asserted Arthur Radcliffe, manager of business development, New Jersey-based Capsugel-Lonza. He explained that the delivery form must be able to prevent premature activation by controlling moisture exposure before ingestion and timed, targeted delivery to the intestines where they work best. Stability of tableted probiotics are compromised from the pressure and heat from the process. Transportation and storage issues—such as length of time, temperature fluctuation and exposure to moisture—can put probiotics in other delivery forms at risk for degradation or early activation. In addition, most probiotics are acid-sensitive, so as they transition through the stomach, moisture and acid can degrade their potency before they reach the intestines.

In capsules, said Radcliffe, “Because HPMC has a low moisture content (4 to 6 percent moisture at 50 percent relative humidity compared to 12 to 14 percent for gelatin), there is low water activity and little for the hygroscopic probiotic to pull from the shell and trigger premature activation before ingestion.” The company’s solution here is Vcaps Plus capsules, with a moisture content as low as 3 percent.

Probiotics are researched and developed to work mainly in the intestinal environment, bypassing the stomach, whose acidic environment can easily destroy vulnerable beneficial bacteria. Capsugel-Lonza’s acid-resistant DRcaps capsules have a unique polymer that protects the capsule from opening in the stomach’s acidic environment, dissolving only when the pH rises above 6.8—the average pH level beyond the stomach. An independent in vivo gamma scintigraphy study of DRcaps capsules, showed at on average, the capsules begin to release in a mean time of 52 minutes after ingestion, when they are passing from the stomach into the small intestine, where probiotics work best, according to Radcliffe.

When formulating a combination supplement offering consumers a probiotic blend with prebiotics, Capsugel-Lonza’s DUOCAPS capsules can deliver both ingredients at different times via the capsule-within-a-capsule technology. The inner capsule contains a probiotic, which is then suspended in a solubilized prebiotic formula that is released first when the outer capsule dissolves.

For those consumers who find it hard to swallow any pill—estimated at between 25 to 35 percent of general population, the Coni-Snap Sprinkle Capsule is an easy-to-open solution. The HPMC capsule opens easily, allowing the probiotic to be sprinkled onto food. “In a study with parents of young children and seniors over the age of 80, participants found the Sprinkle Capsule five times easier to open than a standard capsule,” reported Radcliffe.

This is just a snapshot of occurrences in the brisk evolution of probiotics and prebiotics. R&D will likely accelerate, invigorated by exciting new partnerships (such as the Chr. Hansen mentioned earlier) and acquisitions, such as the UAS Labs purchase of Nebraska Cultures early in April of this year. This acquisition will allow UAS Labs to continue to invest in clinical research and development of DDS-1 strain of L. acidophilus, discovered in 1959 by Dr. Khem Shahani. Additionally, UAS will now provide spore-based probiotics utilizing the well-established ProDURA brand.

Further, the current FAO/WHO (Food and Agriculture Organization of the United Nations/World Health Organization) expert panel definition for probiotics from 2001/2002 has been the accepted reference point for the probiotic industry, according to the International Probiotics Association (IPA). However, because there have been significant technological and scientific advances within the probiotic industry since then, a broader and more clarified scope is required to include these advancements into new guidelines.

This prompted the IPA to announce a proposal for probiotic guidelines pertaining to the food and dietary supplement markets at the 39th session of the Codex Committee on Nutrition and Foods for Special Dietary Uses, held in December 2017. The IPA introduced the proposal to initiate a dedicated “New Work on Harmonized Probiotic Guidelines for Use in Foods and Dietary Supplements.” The work will include updates to the generally accepted probiotic definition.

“As the activities within Codex are strictly regulated and protocol oriented, we expect this work will be long term, but the IPA considers it an essential part of the process for the harmonization of the probiotic framework,” commented George Paraskevakos, IPA executive director. “The new guidelines will provide essential requirements and specifications for probiotics that will not only inform consumers, but also ensure fair practices in food trade with the eventual development of a Codex definition, and the possible progression into a Standard at the Codex level.”

Globally, scientific work continues to explore the microbiome and how the abundance of probiotic strains interact to protect increasingly specific biological structures and functions. Equally, as consumers demand widespread availability of probiotics, the food and beverage industry continues to innovate pleasurable offerings. NIE


1 Majeed et al. Nutrition Journal (2016) 15:21 DOI 10.1186/s12937-016-0140-6.