Prebiotics 2.0: Prebiotic ingredients increasingly target specific bacteria

Photo © AdobeStock.com/barmaleeva

Within the digestive health category, probiotics are so popular that they have transcended from dietary supplements to ingredients in food and drinks. Probiotics, however, are only one piece of the digestive health puzzle. Slowly but surely, prebiotics are being recognized as a necessary component of digestive health. Driving this growth is an overall interest in fiber consumption.

“Innova Market Insights called out fiber as a key trend for 2019, noting that 44% of U.S. consumers were increasing their fiber consumption,” says Taylor Halstead, product manager for specialty carbohydrates, Cargill (Minneapolis, MN). “Those numbers track with consumer research from the International Food Information Council’s (IFIC) 2019 Food & Health Survey, which noted that more than 85% of consumers view fiber as healthy.”

Consumer understanding of prebiotics is less pronounced but growing as more products hit the market and get media coverage. While there is surely a lot of room for prebiotic sales to grow, and for consumers to learn about prebiotics’ function, the market is seeing some traction-albeit, from a still-smaller sales base.

“In the first half of 2019, media coverage on prebiotics was 12% greater than the prior year for the same period. Social media is driving this increase,” explains Samantha Ford, business development director at AIDP (City of Industry, CA), citing data from Meltwater market research. “Many consumers are unaware of the role prebiotics play in digestive health; however, media coverage is helping to drive consumer interest.” Ford says that according to a recent Nutrition Business Journal report, in 2018 probiotic sales grew about 8% while prebiotic sales grew over 130%.

“Clearly, there is growing consumer interest in prebiotics,” Ford says. And let’s not forget: “Most consumer diets do not contain enough fiber.” For prebiotic firms, the challenge is educating consumers on how supplemental prebiotics can complement the diet, “without the effects of large amounts of fiber,” she says.

Prebiotic: An Increasingly Targeted Approach

The general nature of prebiotics is that they feed gut bacteria to promote healthy-bacteria growth. As the digestive category evolves and becomes more sophisticated, the notion-and exploration-of prebiotic supplementation is becoming much more selective in terms of targeting specific bacteria, both as a standalone supplement and in a synbiotic formulation that combines prebiotics and probiotics.

This targeted approach to prebiotics has the potential to profoundly change the digestive health space and shake up the probiotic category. “We are already seeing these concepts disrupt the market,” says Ford. “For example, ‘probiotic-free’ digestive health formulas are becoming more and more popular.”

Over time, should this targeted approach to prebiotics become more accepted, probiotic consumers may find themselves moving toward the novel prebiotics market, perhaps encouraging probiotic manufacturers to take the growing prebiotic space into stronger account-if they haven’t begun doing so already.

When Prebiotics Work Well…or Not

Prebiotics have a long history of helping to maintain the human microbiome, with mother’s milk being rich in over 200 types of oligosaccharides, one of the main prebiotic types. Our ancestors consumed a great deal of oligosaccharides by eating roots, tubers, and foraging for fruits and nuts, explains Kiran Krishnan, chief scientific officer of digestive-product brand Microbiome Labs (St. Augustine, FL). Eventually, it became thought that the type of prebiotic is an important factor in just how successfully these ingredients maintain the gut microbiome, Krishnan says.

For instance: A frequent complaint of prebiotics is intolerability, with some suffering from discomfort related to gas and bloating after consuming prebiotics. “The problem is that when you start using prebiotics that aren’t specific to certain groups of bacteria, you end up with food for bacteria that can be consumed and metabolized by lots of different groups of bacteria in the gut,” says Krishnan. That means that if one’s microbiome is already out of balance, some prebiotics may actually feed undesirable bacteria.

According to Krishnan, the ideal characteristic of a prebiotic is for it to have a high degree of polymerization (DP), which determines how far into the bowel the prebiotic will survive.

“A prebiotic with a high DP means it’s a very complex carbohydrate, and because of that complexity there is a very narrow range of bacteria that have the right enzymes to be able to break down and metabolize that carbohydrate,” he explains. “Most of those bacteria that tend to have very sophisticated enzymatic capability to break down complex carbs exist in the large bowel.” Akkermansia and Bifidobacteria are two bacterial strains that exist in the large intestine that are capable of breaking down complex carbohydrates. A high-DP prebiotic is less likely to get broken down by bacteria before it can do its job.

In contrast, prebiotics with low DP tend to be broken down by a wider range of bacteria and sooner in the bowel, causing overgrowth in the small intestine, which is particularly bad if someone is already suffering from small-intestine bacterial overgrowth.

Microbiome Labs, for example, has a prebiotic formula that combines four oligosaccharides that have high DP and have been shown in clinical trials to specifically feed good bacteria and keystone strains such as Akkermansia muciniphila, Faecalibacterium prausnitzii, and Bifidobacteria. Called MegaPreBiotic, the product is composed of galacto-oligosaccharides in the form of Bimuno (an ingredient manufactured by Clasado BioSciences; Jersey, UK), fructo-oligosaccharides in the form of Livaux and Actazin (ingredients distributed by AIDP Inc.), and xylo-oligosaccharides in the form of PreticX (also distributed by AIDP).

Xylo-oligosaccharides, like PreticX, boost the levels of Bifidobacteria. One of the major benefits of such products is the low effective dose required to feed beneficial bacteria, says AIDP’s Ford. “The PreticX clinical research studies have also found a significant increase in the Bacteroides fragilis strain (a member of the Bacteroidetes family) with 2 grams per day,” says Ford. “The team also concluded that PreticX supplementation did not increase Lactobacillus (a member of the Firmicutes family). These findings suggest that PreticX supplementation may result in a beneficial Bacteroidetes:Firmicutes ratio that could lead to a better metabolic response and benefits to weight management.”

For example, it has been observed that obese individuals have elevated Firmicutes and a reduced population of Bacteroides, while the reduction of Firmicutes and elevation of Bacteroides has been associated with weight loss.¹

Livaux, made from the Zespri SunGold brand of kiwifruit, is associated with an increase of Faecalibacterium prausnitzii bacteria. F. prausnitzii is the most abundant anaerobic bacteria in the colon, making up about 5% of the bacteria in feces, according to a meta-analysis² conducted by Metagenomics of the Human Intestinal Tract, a project financed by the European Commission to establish associations between the genes of the human intestinal microbiota and human health and disease. It has also been observed that people with inflammatory bowel disorder (IBD) have significantly less F. prausnitzii bacteria than healthy individuals.³ Because the bacteria is anaerobic and cannot survive in oxygen, F. prausnitzii cannot be taken as a probiotic and therefore must be fortified through the use of prebiotics.

The reason F. prausnitzii may be beneficial for people with IBD is because one of the end products created when glucose is fermented by the bacteria F. prausnitzii is a substantial amount of butyrate. Butyrate plays a major role in gut physiology, protection against pathogens, and modulation of the immune system. Increasing levels of butyrate by increasing levels of F. prausnitzii by using a related prebiotic can therefore aid butyrate’s benefits³. Butyrate is also the primary energy source of intestinal epithelial cells, a fundamental element for maintaining the integrity of the intestinal barrier. Researchers also note that butyrate contributes to anti-inflammatory effects.

Actazin, made from Zespri-brand green kiwifruit, says AIDP, is rich in naturally occurring soluble and insoluble fiber, polyphenols, and the enzyme actinidin. The ingredient supports regular bowel movements with no change in the Bristol Stool Scale, and has a low dose of 600 mg per day. In one study, supplementation with Actazin (2400 mg per day) resulted in a significant increase in mean daily bowel movements⁴. In a subgroup of participants that experienced an increase of at least one bowel movement per week, supplementation with 600 mg of Actazin per day was shown to be associated with significant increases in daily bowel movements.

Still Synbiotics

While there are a great deal of benefits of using prebiotics as standalone products, consumers still value probiotics, and therefore manufacturers are seeking to pair prebiotic fibers with probiotic bacteria to create synbiotic formulas. Cargill, for example, recently announced a new grade of its branded Oliggo-Fiber chicory root fiber called Oliggo-Fiber XL Ultra, which is designed to have low water activity, enabling its use as a blending excipient with probiotics, which are sensitive to moisture. “As a result, our XL Ultra offers enhanced stability of the probiotic culture compared to standard inulins or other fibers,” says Halstead.

“As a prebiotic, [chicory root fiber] enhances the growth of Lactobacillus and Bifidobacterium species,” he adds. “Consuming 5 grams of chicory root fiber per day stimulates the microflora in the digestive tract, helping to maintain a neutral balance.”

Another unique source of prebiotic fiber ideal for pairing with probiotics is cranberry seed powder, such as that manufactured by Fruit d’Or Nutraceuticals (Villeroy, QC, Canada). Like most prebiotic fibers, the cranberry seed powder acts as a food source for probiotic bacteria, but it contains other important nutritional components, too. “It feeds certain probiotic strains, such as Bacillus coagulans,” explains Stephan Lukawski, director of sales and business development for Fruit d’Or Nutraceuticals. “Cranberry seed powder contains protein fiber and all the essential amino acids, as well as omega-3, -6, and -9, along with [proanthocyanidins] and other polyphenols. Cranberry seed powder is about polyphenols, not just fiber.”

In addition to feeding beneficial probiotic bacteria, studies have shown that cranberry seed powder inhibited the growth of negative bacteria such as E. coli. Cranberry seed powder’s ability to feed beneficial bacteria and inhibit the growth of negative bacteria has been demonstrated in clinical research of an ingredient that combines the cranberry seed powder with the patented probiotic strain Bacillus coagulans MTCC 5856 (LactoSpore by Sabinsa; East Windsor, NJ).⁵ This trademarked combination ingredient is called LactoCran.

The polyphenol aspect is important to keep in mind because polyphenols have a great deal of potential in the digestive health space as well. Lukawski points out that polyphenols also play an important role in the gut-brain-immune axis.

“Moving forward, the winners in the probiotic space are those manufacturers who conduct research with other science-based ingredients,” states Lukawski. “For example, polyphenols in fruit, such as cranberry and blueberry, will play a significant role with probiotics. Gut health and brain health will be connected with blueberry. Gut health and immune health will be connected with elderberry, and gut health and the prevention of urinary tract infections are connected with cranberry.”

Krishnan shares a similar sentiment: “The next big thing is, as prebiotics start to get more awareness and people start becoming more aware of it and it sees its day in the spotlight, the next thing is the importance of polyphenols in the microbiome. There are studies that have been coming out over the last year or so on the role of polyphenols in the microbiome, which is not very well understood, and as it turns out, polyphenols are prebiotics of their own. Polyphenols also provide the base building blocks for a lot of important compounds that the microbiome produces for the host.”

Microbiome Labs has even begun incorporating polyphenols in its product called MegaMucosa, which is a mucosal-rebuilding product. “We use a citrus polyphenol mix that has been shown in clinical studies to significantly reduce intestinal permeability, increase [bacterial] diversity, and reduce inflammation in the mucosa, just from the use of the polyphenol alone,” says Krishnan.

New Take on Prebiotic

Another way to selectively fortify gut bacteria is through supplementation with bacteriophages. Bacteriophages are often described as viruses that target negative bacteria. This represents yet another, different approach to prebiotics.

“Phages are minuscule bundles of DNA or RNA enrobed in a protein shell,” explains John Deaton, PhD, vice president of science and technology, Deerland Probiotics and Enzymes (Kennesaw, GA). “Phages are diverse and abundant, found in seawater, soil, humans, and fermented foods-and there are 10-fold more phages than bacteria populations in the human body. Unlike probiotic bacteria, a bacteriophage (‘phage’) is not a living entity. However, phages are active.” Deerland’s novel PreforPro bacteriophage reproduce themselves by targeting and utilizing specific unwanted or pathogenic living bacterial cells as their host. When a phage takes control of its host, it takes command of the undesirable bacterial cell’s metabolic processes, rapidly producing bacteriophage progeny which destabilize the cell wall to escape and seek out more bacteria host cells. “This effectively reduces the population of the host bacteria, providing more room for good bacteria (probiotics) to proliferate, thus improving host health,” says Deaton.

In a study published in Nutrients, researchers found that a 15-mg-per-day dose of the bacteriophage PreforPro for 28 days reduced the presence of E. coli and increased specific bacteria populations in the process.⁶ More specifically, the phage increased Bifidobacterium bifidum, Lactobacillus delbrueckii, and the butyrate-producing Eubacterium. Additionally, there was a significant decrease in the pro-inflammatory cytokine interleukin 4.

There is also the potential of using bacteriophage in combination with probiotic bacteria, with over 20 studies showing the ingredient’s ability to promote the growth of beneficial bacterial strains.

“Both in vitro and in vivo tests have demonstrated the growth-promoting effect of PreforPro on beneficial bacterial strains of Lactococcus, Lactobacillus, Bifidobacterium, and Bacillus subtilis when competing with undesirable bacterial strains,” says Deaton. “In several in vitro tests under physiological conditions, PreforPro has been shown to accelerate the growth of numerous wide-ranging probiotic species, including: B. bifidum, B. breve, B. animalis, B. longum, L. acidophilus, L. paracasei, L. casei, L. rhamnosus, Lactococcus lactis, and B. subtilis.”

References:

1. Mariat D et al. “The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age.” BMC Microbiology, vol. 9 (2009): 123
2. Arumugan M et al. “Enterotypes of the human gut microbiome.” Nature, 473(7346): 174–180
3. Cao Y et al. “Association between Faecalibacterium prausnitzii reduction and inflammatory bowel disease: A meta-analysis and systematic review of the literature.” Gastroenterology Research and Practice. Published online ahead of print on March 27, 2014.
4. Ansell J et al. “Kiwifruit-derived supplements increase stool frequency in healthy adults: a randomized, double-blind, placebo-controlled study.” Nutrition Research, vol. 35, no. 4 (2015): 401-408
5. Majeed M et al. “Cranberry seed fibre: a promising prebiotic fibre and its fermentation by the probiotic Bacillus coagulans MTCC 5856.” Food Science and Technology, vol. 53, no 7 (2018): 1640-1647
6. Febvre HP et al. “PHAGE study: Effects of supplemental bacteriophage intake on inflammation and gut microbiota in healthy adults.” Nutrients, vol. 11, no. 3 (2019)