Sean Moloughney, Editor03.02.15
The community of bacteria living in the human body consists of about 100 trillion microorganisms, which influence health and play a role in the development of many diseases.
At least 1,000 different species of bacteria make up the population of microbes living in the intestines. While one third of this “gut microbiota” is common among most people, two thirds are specific to each individual, effectively leaving a fingerprint of intestinal well-being.
Research in this field has accelerated recently. In January, researchers from 30 organizations and 15 countries started working together on a new project called MyNewGut, which is designed to study the human gut microbiota, its genome (microbiome) and their roles in human physiology. The project receives funding from the European Union’s Seventh Framework Program.
“Our challenge is to provide a proof of concept that dietary interventions with food and ingredients designed to modulate the gut microbiota can contribute to controlling and reducing the incidence of diet-related diseases, such as obesity, metabolic syndrome and behavioral disorders—epidemics in our developed society,” said Yolanda Sanz, MyNewGut’s project coordinator.
Officially launched in December 2013, MyNewGut is a five-year multidisciplinary project. While organizations around the world have been studying this field for many years, this marks the first time an EU-supported initiative has brought together such a unique consortium of experts from various scientific and industrial disciplines in order to investigate the microbiome’s influence on human health and disease.
Following an interdisciplinary strategy, this project will gather the work of experts in brain research, computational modeling, immunology, microbiology, nutrition, physiology, and technologies such as metagenomics and metabolomics.
Health Origins & Implications
Recent research has indicated that gut bacteria can impact wellness beginning at birth. For example, a study published in February in mBio, the online open-access journal of the American Society for Microbiology, suggested environmental factors like duration of gestation and method of delivery can influence the rate at which infants’ gut bacteria mature, which can have implications for how babies grow and put on body fat.
For this study, scientists from Nestlé working in the First 1000 days and Healthy Kids research program at Nestlé Research Center, in collaboration with EpiGen researchers, used a technique called 16s ribosomal RNA sequencing to analyze the microbial composition of stool samples collected from infants at three days, three weeks, three months and six months of age.
Findings suggested factors before and at birth influence the development of the intestinal microbiota, and this in turn may influence the amount of body fat later in life. Researchers still can’t fully explain this relationship and further studies will be needed to delineate the mechanisms underlying these phenomena. However, the results provided further confirmation that components of the early gut microbiota are strongly influenced by environmental factors, even in healthy infants.
Future study and understanding could eventually lead to the development of nutritional products for expecting mothers, researchers suggested.
In January, Nestlé Health Science also completed a CHF 65.6 million investment in Seres Health Inc., Cambridge, MA, a microbiome therapeutics company that is developing a novel class of biological drugs designed to treat diseases by restoring the function of the microbiome.
“Hippocrates, considered the founder of modern medicine, was the first to consider the importance of the gut to overall wellness by suggesting that all disease began in the gut,” noted David Daguet, PhD, scientific manager at Nexira, Rouen, France.
One the most complex microbial ecosystems, the gut is “a diverse community of different bacteria types that play a vital role in fighting external factors that can negatively impact health, and play an instrumental role in maintaining health via the absorption of food and nutrients,” said Patrick Luchsinger, nutrition marketing manager, Ingredion Incorporated, Westchester, IL.
The most basic implication of a healthy gut on overall health and wellness is maintenance of normal nutritional status and effective absorption of food, water and minerals while fighting harmful foreign substances that enter the body through the gastrointestinal (GI) tract and easing their elimination, he said.
“Our knowledge of the resident species and their potential functional capacity is rapidly growing with each published paper,” Mr. Luchsinger added. “This impacts the nutraceutical ingredient market as it is furthering our understanding of the role of gut microbes, leading to science-driven new product development.”
Dr. Daguet emphasized the key role the microbiota plays in efficient nutrient absorption. “Through the process of fermentation, gut bacteria metabolize various nutritional substrates to end products. Under certain circumstances such as diet, medication, stress, age and general living conditions, the balance of the gut microbiota may be altered, leading to digestive discomfort like indigestion, irregular transit (diarrhea, constipation) or abdominal pain, to more serious conditions like irritable bowel syndrome (IBS), which afflicts nearly 30% of the U.S. population and 20% worldwide.”
About 60-70 million people suffer from digestive diseases in the U.S., according to the National Institutes of Health. Dr. John Deaton, vice president of technology, Deerland Enzymes, Kennesaw, GA, noted that, according to the American Gastroenterological Association (AGA) Institute, good digestive health describes appropriate nutrient absorption, intestinal motility, immune function and a balanced microbiota.
“Research over the past two decades has revealed that gut health is critical to overall wellness and immunity, and that an unhealthy gut contributes to a wide range of health challenges,” Dr. Deaton said. “I’ve seen the evidence of this in my own research, through clinical studies on our various products designed to support digestion. Our studies have shown that numerous health conditions beyond digestive discomfort can be affected when digestion is optimized with the aid of a dietary supplement—for example, reduced frequency of headaches or even general physical pain.”
Many researchers believe supporting digestive health and restoring the integrity of the intestinal barrier will be “one of the most important goals of health professionals in the 21st century,” Dr. Deaton added.
The digestive system is “ground zero” for many of the body’s vital functions, according to Michael Bush, senior vice president, Ganeden Biotech, Mayfield Heights, OH. “We all understand the role the gut plays in breaking down nutrients but there is growing evidence showing a link between gut health and the proper function of the immune system, reduction in inflammatory processes, mood regulation and metabolic processes.”
Research into understanding of gut bacteria has raised more questions, he added. “With over 10 times as many bacterial cells in the gut than make up the entire human body, we have to learn to live in harmony with our gut bacteria and nurture it to ensure that the microbiome is able to do its job unencumbered.”
Recent scientific discoveries have related to obesity, depression, stress, kidney health, cardiac health and a variety of other very specific areas, Mr. Bush noted. “In the not-so-distant future you may see food, beverage and supplement products coming to market with probiotic bacteria selected to address these specific areas.”
With a more dynamic understanding of the gut microflora ecosystem, new product development will expand into more symbiotic/synergistic products, such as functional foods and beverages that combine both probiotics and prebiotics, Mr. Luchsinger predicted.
However, the application has to make sense for the consumer. “Dairy (yogurt, dairy-based beverages) nutritional bars, healthy snacks and juices are good applications for functional foods because of the healthy connotation and association to gut health. Consumer acceptance will be much greater if these applications are further enhanced by probiotics, prebiotics or a combination of the two.”
The gut functions as the “front line of the body’s immune system,” said Dan Lifton, president, Maypro Industries, Purchase NY, noting 70% of the body’s immune cells reside in the gut. “The gut is also a communications center utilizing nerve cells to provide signals to the brain, which regulates hunger and controls weight gain. The gut is also responsible for the production of key hormones such as serotonin, which regulates mood, sleep and stress. The implication of these connections is that you cannot take care of your health without taking care of your gut. And on the flip side, many health problems can be addressed by addressing gut health.”
Each person’s gut bacteria profile is unique. However, understanding about characteristics of certain communities of bacteria may lead to development of novel personalized nutraceutical products, Mr. Lifton added. “I believe that the newly gained understanding of the gut microbiome has become the most compelling reason to pursue research in personalized medicine and to develop novel function-specific nutraceuticals.”
Dr. Daguet agreed, noting that understanding of the intestinal microbiota has increased significantly, “due to the recent developments in analytical techniques to analyze the composition of complex microbial ecosystems.”
“Several disorders have been associated with an altered composition of the gut bacteria,” he added. “As a consequence, the microbiota is increasingly recognized as a therapeutic target to improve health and wellness.”
For example, Faecalibacterium prausnitzii has recently been identified as an important gut bacterium that may be associated with Crohn’s Disease.
“For the nutraceuticals market, these findings open new growth opportunities,” Dr. Daguet said. “Gut health products could be able to target more consumers on a wide range of wellness applications such as cardiovascular, cognitive function, weight management, eczema, stress, etc. Recent studies have shown very interesting results in this field.”
Breaking Down Digestive Health
Sales of digestive remedies have grown 7% globally since 2008, reaching $15.7 billion in 2013, according to Euromonitor International. Market drivers include contemporary lifestyle trends (both healthy and unhealthy), aging populations and consumer awareness of digestive health conditions.
Dr. Daguet also noted that more consumers are connecting digestive health with general well-being. “Dietary fibers, prebiotics, probiotics or symbiotic dietary supplements, with more precise dosage and offering optimum comfort and tolerability are definitely highly relevant industry and consumer trends.”
Within the overall supplements market, natural ingredients with organic certification, clean label and being “naturally functional” are also major trends, he noted. “Fibregum from Nexira is an all-natural, organic and GMO-free source of 90% soluble dietary fiber coming from 100% natural acacia gum. Fibregum is recommended for clean label products and offers scientifically proven benefits. Clinical studies have demonstrated its numerous health benefits, including its action on digestive comfort and its prebiotic properties.”
Ingredion manufactures NutraFlora prebiotic fiber, a short chain fructooligosaccharide (scFOS). More than 34 human studies as well as numerous in vitro studies demonstrate the beneficial effects of scFOS on digestive and immune health, according to the Ingredion’s Mr. Luchsinger.
“NutraFlora’s short chain structure with glucose termination narrows the fermentation profile and while the good bacteria preferentially ferment NutraFlora scFOS, it does not allow for use by pathogens. Since pathogenic bacteria in the gut cannot ferment NutraFlora, it fosters an environment that favors competitive inhibition of pathogens. When Bifidobacteria species increase, pathogens tend to decrease in number.”
Nena Dockery, technical services manager for Stratum Nutrition, St. Charles, MO, said proper function of the digestive system is vital to overall health. “The digestive tract, beginning in the mouth, is the route through which all nutrients, critical for sustaining life and supporting optimal health, enter the body, are broken down into their readily absorbable forms, and enter into systemic circulation. The digestive tract also provides the means through which many harmful substances are prevented from entering the body’s systemic circulation.”
Two areas of digestive health that directly impact overall wellness include the efficiency of food breakdown and the condition of the intestinal wall, which includes the makeup of the gut microbiota.
“For food to be absorbed into circulation, it must first be broken down into components that are readily absorbed,” said Ms. Dockery. “This function is mainly performed by the action of gastric acid and digestive enzymes. If food is not sufficiently broken down in the stomach and upper small intestine, the most obvious repercussion is digestive distress, including cramping and bloating.”
“In addition, incomplete food breakdown limits nutrient absorption, which can ultimately impact the functioning of metabolic processes,” she continued. “In some individuals, undigested food can put stress on the intestinal wall, causing it to become more permeable to larger food fragments and even pathogens, allowing them to enter into circulation (a condition sometimes referred to as leaky gut syndrome). The presence of these fragments outside the digestive tract can lead to an immune system response, resulting in multiple ramifications in the body, including the development of food allergies and other autoimmune conditions.”
Better understanding of fiber types has led to improved product development, Ms. Dockery noted. “Kiwifruit contains both prebiotic fiber and a select group of polyphenolic compounds and has been shown to deliver both an effective and very gentle laxative effect.”
Stratum Nutrition offers a cold-pressed kiwifruit ingredient, ACTAZIN, which provides the benefits of premium New Zealand green kiwifruit in a powdered form. “ACTAZIN exhibits protein-digesting enzyme activity from its inherent actinidin content to help facilitate optimal protein digestion. The concentrated powder also contains more than 10% fiber in both soluble and insoluble forms. And it has been shown to exert an advantageous prebiotic benefit when combined with probiotics without promoting the growth of less desirable intestinal bacteria.”
Probiotics Proliferate
Substantial evidence has confirmed probiotic bacteria help support gut health. However, Ganeden’s Mr. Bush noted that benefits are specific to individual strains. “Ganeden’s patented strain, GanedenBC30 has been shown in multiple studies to support gut health through mechanisms such as gut pH lowering, bacteriocin production and helping provide an environment that is conducive to the growth of other native gut bacteria.”
Consumers are increasingly more health conscious, and they continue to look for convenient, great-tasting, lifestyle-friendly functional foods and beverages. “We have seen just the tip of the iceberg when it comes to innovation, and we believe the next few years will bring even more innovative applications and delivery systems centered around science-backed ingredients, driven by consumer demand.”
Probiotic-fortified food and beverage products for children, athletes, women and active seniors have gained popularity of late, Mr. Bush noted. “Consumers are no longer interested in taking another pill; they want to receive the benefits of probiotics while consuming something they already enjoy, and without having to adjust their daily routine. Products that offer more than one functional use—such as a probiotic-fortified sports nutrition shake that also supports digestive and immune health, or probiotic-fortified hot beverages such as tea and coffee that not only give the consumer their morning pick me up, but also their daily dose of probiotics—are trends where we have seen tremendous growth.”
Tim Gamble, president and CEO, Nutraceutix, Redmond, WA, agreed that a healthy digestive system is instrumental to overall wellness. “Clearly, if we are to gain benefits from dietary supplements and functional food ingredients, a properly functioning and highly capable digestive system are key. Due to the last few years of research, it is becoming widely recognized that gut health and a healthy, balanced gut microbiota, is related to a wide variety of systemic benefits, not just those traditionally associated with digestion.”
Education efforts have helped influence consumer awareness of probiotics, Mr. Gamble added, “along with continued investigation by researchers, health practitioners and quality conscious brands into, ‘What makes a good probiotic?’ This is the next logical step after what has been an introductory period characterized by the question, ‘What is a probiotic?’”
For more than two decades, Nutraceutix has been leading education efforts as a producer of natural probiotic organisms, and in recent years, with pioneering work on the proper delivery of live probiotics to the digestive tract. “This work, widely known as the assortment of BIO-tract delivery technologies, makes a wide variety of probiotics in dietary supplements better than ever, and is now recognized by over 30 patents worldwide, with many more patents pending.”
Probiotics are leading the gut health category, and for good reason: supporting research is convincing and the modes of action are clear, said Maypro’s Mr. Lifton.
“Maypro’s original bifidobacterium strain Morinaga BB536 is supported by more than 40 human clinical studies and works by supporting a healthy balance of bacteria in the GI tract and increasing short chain fatty acids. Maypro also distributes ProDURA—a spore-forming Bacillus coagulans strain clinically shown to assist in reducing total cholesterol levels and supporting the health of the vaginal and gastrointestinal tracts. When spores encounter the ideal conditions of temperature, moisture and pH in the large intestine, they revert to their active form.”
Gut health is really the basis for general good health, according to Michael Shahani, COO, Nebraska Cultures, Walnut Creek, CA, which manufactures ProDura. “It’s not only about absorption of nutrients but also how you keep out unhealthy bacteria.”
Overall, health has declined due to overconsumption of processed foods, over-prescription of antibiotics and other environmental stressors that can compromise the integrity of gut microbiota. “Having a healthy balance of good bacteria is really essential,” he said.
“Probioic bacteria are mostly what we call transient bacteria,” he noted. “We take them in through food or supplements, but they go away; they don’t live there forever. A certain amount does, but our bodies are designed to take nutrients in through food or fermented sources.”
While consumer awareness for specific probiotic strains has grown, along with demand for fortified foods and beverage, companies are challenged to deliver an efficacious dose at the time of consumption.
Mr. Shahani said Nebraska Culture’s ProDura brand offers good survivability at high temperatures for various products.
Companies also need to consider what type of probiotic foods consumers will pay a premium for, suggesting the health halo around dark chocolate has presented an interesting option for the probiotic market.
Overall, manufacturers of proprietary probiotic strains have made significant investments in clinical studies and major food companies have helped raise awareness of the benefits of probiotics, said Mr. Lifton. “However, the complexity of the probiotic ingredients and the sheer number of choices available have created challenges for the consumer. As a result, many brands moved to using high CFU (colony forming unit) counts as a point of differentiation, leading to what I call the battle of ‘millions, billions, trillions.’ Our strategy with the Morinaga BB536 strain was to focus on the availability of the clinical data and the stability at room temperature after two years, which enables brands to claim potency at date of expiry rather than date of manufacture. The stability story also applies to spore-forming probiotics such as ProDURA, which can be used in a variety of delivery forms, including gummies, beverages and foods.”
In terms of application format, probiotic-rich dairy products have already penetrated the market successfully, said Mr. Lifton. “We expect the category to continue its growth. However, consumer awareness of probiotics has reached such a level that you start to see digestive health ingredients in less obvious delivery forms. Kevita, for example, launched a line of sparking probiotic drinks that have strongly resonated with consumers. We expect those trends to continue as other innovative brands develop novel products in the category.”
In addition to its probiotic range, Maypro distributes Benegut, a patented extract of perilla leaf the company claimed has anti-spasmodic and anti-inflammatory properties clinically shown to reduce bloating.
Experts have identified the inheritance, composition, balance and health of the intestinal flora as major contributors to overall health and wellness, said Mike Petteruti, vice president, Gnosis USA Inc., Doylestown, PA, having direct implications for skin, cardiovascular, metabolic autoimmune disorders and even psychological conditions. “As a company, Gnosis has proven a commitment to performance-based nutritional products, and our BioOptima is our proprietary Saccharomyces boulardii product that has been shown to address the importance of gut flora composition and balance in humans.”
Safety, efficacy, consistency and stability are all important considerations, he added. “There are opportunities to examine benefits of combination products, but even before this, there is significant technical, manufacturing and clinical ‘innovation’ to be done to establish the reliability of currently promoted products.”
Mechanisms & Research
Certain probiotics are very effective in facilitating the digestive process through multiple mechanisms, including immune functioning and digestive enzyme production, according to Stratum’s Ms. Dockery. “Supplementing with probiotics or prebiotics that feed indigenous bacteria can be very therapeutic in improving gut health. It must be kept in mind that intestinal bacteria are particularly prone to the actions of antibiotics. Therefore, after a course of antibiotics, it is important to supplement with a probiotic and/or a prebiotic to restore the gut to homeostasis.”
Whole food sources have always been a preferential way to consume nutrients, she added, though they are not always as practical or convenient as supplements. “In some ways, functional foods and beverages can provide the best of both worlds. They are especially suited to gut health products such as fiber supplements that require more than a gram of active ingredient. High fiber food bars and clear liquid fiber beverages have enabled this often neglected nutrient to be consumed in ways that are much more palatable for many consumers.”
Since different strains offer specific benefits, Dr. Deaton said his customers are increasingly seeking a multi-strain formulation of both non-spore and spore-forming probiotics. “Based on this demand, more science is emerging to support the benefits of spore forming probiotic strains, such as Bacillus subtilis. Deerland Enzymes has genome sequenced for safety and clinically tested for efficacy DE111, a highly effective strain of Bacillus subtilis, a very stable probiotic spore that supports digestive health and works as a complement to many of the non-spore strains that are also available. The genome sequencing confirmed the strain contained no plasmids, antibiotic resistant or deleterious genes. The human clinical study showed the strain’s ability to control microbial populations, aid in digestion and maintain general health.”
In addition, research has shown certain prebiotics can increase the benefits of probiotics, he said. However, fiber-based prebiotics often come along with several drawbacks. “In response to this growing trend, Deerland Enzymes’ research and development team recently introduced a unique prebiotic that is not fiber or starch based, is highly effective in small doses (15 mg) and does not exhibit any of the drawbacks of more commonly used prebiotics. This patent-pending product, called PreforPro, is backed by a human clinical study, as well as both in vitro and in vivo studies that demonstrate its superiority to the typical prebiotics that have been used to date.”
Bérengère Feuz, marketing group manager, Lallemand Health Solutions, Montreal, Quebec, Canada, said technological advances in strain protection and fermentation processes have ensured more stable, heat- and acid-resistant probiotic yeast and bacteria, which enable innovative forms for increased convenience and versatility (e.g., liquids, powders, orodispersible sticks, chewables and products that no longer require refrigeration). “On the other side, scientific research has recently reached a new level with hundreds of high quality publications produced each year, and this also contributes to the reputation and success of the product category.”
Lallemand offers Lacidofil, a combination of Lactobacillus Rosell-52 and Lactobacillus Rosell-11. Both individual strains and their combination have been the subject of extensive research over the years. At least 23 human studies have been published to date, according to Ms. Feuz. “Lacidofil primary indications are in the area of gut health, with several positive studies in antibiotic-associated diarrhea prevention in children and adults, H. pylori eradication, acute gastroenteritis in children, management of IBS symptoms and lactose intolerance.”
The company’s Protecflor probiotic formula combines the synergistic activities of three well-documented Rosell bacteria strains with Saccharomyces boulardii probiotic yeast. Protecflor is recommended for reinforcing or restoring the intestinal barrier and for fighting intestinal infections, in particular traveller’s diarrhea, Ms. Feuz noted.
Additionally, a randomized, double-blind, placebo-controlled trial on daily intake of Bifidobacterium bifidum R0071 conducted at the University of Florida with 581 participants was published ahead of print by the British Journal of Nutrition. Research demonstrated a 45% reduction of the likelihood that a participant would report a cold/flu while on the probiotic compared to placebo.
The clinical study evaluated the individual effects of three probiotic strains—Bifidobacterium bifidum Rosell-71 (R0071), Bifidobacterium infantis Rosell-33 (R0033), Lactobacillus helveticus Rosell-52 (R0052), which are found in combination in the company’s ProbioKid formulation and have been previously shown to reduce the occurrence of common winter infections in school-aged children by 25% and absenteeism by 40%.
Enzyme Answers
Enzyme supplements continue to gain recognition among consumers, according to Deerland’s Dr. Deaton. “Bioavailability is a key consumer concern and the ability to breakdown food into its basic and useful components is of critical concern for consumers interested in functional nutrition for growth, development and supporting healthy aging.”
Digestive enzymes break down food-derived fats, carbohydrates and proteins into components the body can use. “During cooking and processing, the natural enzymes present in raw foods are denatured,” said Dr. Deaton. “In addition, our bodies don’t produce the enzyme cellulase at all; this is an enzyme that breaks down the cell wall of plants, releasing the nutrients for our bodies to absorb. Those who follow a vegetarian or vegan diet are likely missing out on key nutrients from the plant-based foods they’re eating, and would most certainly benefit from an enzyme supplement.”
Moreover, consumers are recognizing they may have difficulty with normal digestion of wheat and dairy. Eighteen million Americans believe they have difficulty digesting gluten, according to the Center for Celiac Research and Treatment. Meanwhile, 50 million people report discomfort due to ingestion of dairy products, according to the American Gastroenterological Association.
“To address the growing demand for products that address food sensitivities, Deerland Enzymes’ latest products Glutalytic and Dairylytic have been designed to optimize digestion of gluten and dairy proteins,” said Dr. Deaton. “These enzyme-based products hydrolyze wheat and dairy proteins and break them down into smaller constituents so they can be more easily managed by the body. Glutalytic helps minimize the unintended consequences of inadvertent gluten consumption, and is supported by a human clinical study. Dairylytic works to help break down not only the lactose associated with dairy foods, but also the proteins that can be difficult to digest and may cause discomfort to sensitive individuals. Fewer dietary restrictions can yield huge quality of life benefits.”
Bret Wyant, vice president of sales, American Laboratories, Inc., Omaha, NE, also acknowledged the importance of probiotics, prebiotics and enzymes, which can aid the digestion of proteins, carbohydrates and sugars to ease digestive discomfort or bloating symptoms that result from eating common foods and vegetables.
“American Laboratories promotes several functional enzymes for the ease of digestive discomfort that is found when consuming items like dairy and vegetables. We have found a large, growing interest in supplementing probiotic formulas with enzymes like alpha-galactosidase (digests fibers associated with beans/legumes), lactase (digests milk sugars for issues common to lactose sensitivity) and glyprozyme (functional enzyme blend for issues common to gluten sensitivity).”
At least 1,000 different species of bacteria make up the population of microbes living in the intestines. While one third of this “gut microbiota” is common among most people, two thirds are specific to each individual, effectively leaving a fingerprint of intestinal well-being.
Research in this field has accelerated recently. In January, researchers from 30 organizations and 15 countries started working together on a new project called MyNewGut, which is designed to study the human gut microbiota, its genome (microbiome) and their roles in human physiology. The project receives funding from the European Union’s Seventh Framework Program.
“Our challenge is to provide a proof of concept that dietary interventions with food and ingredients designed to modulate the gut microbiota can contribute to controlling and reducing the incidence of diet-related diseases, such as obesity, metabolic syndrome and behavioral disorders—epidemics in our developed society,” said Yolanda Sanz, MyNewGut’s project coordinator.
Officially launched in December 2013, MyNewGut is a five-year multidisciplinary project. While organizations around the world have been studying this field for many years, this marks the first time an EU-supported initiative has brought together such a unique consortium of experts from various scientific and industrial disciplines in order to investigate the microbiome’s influence on human health and disease.
Following an interdisciplinary strategy, this project will gather the work of experts in brain research, computational modeling, immunology, microbiology, nutrition, physiology, and technologies such as metagenomics and metabolomics.
Health Origins & Implications
Recent research has indicated that gut bacteria can impact wellness beginning at birth. For example, a study published in February in mBio, the online open-access journal of the American Society for Microbiology, suggested environmental factors like duration of gestation and method of delivery can influence the rate at which infants’ gut bacteria mature, which can have implications for how babies grow and put on body fat.
For this study, scientists from Nestlé working in the First 1000 days and Healthy Kids research program at Nestlé Research Center, in collaboration with EpiGen researchers, used a technique called 16s ribosomal RNA sequencing to analyze the microbial composition of stool samples collected from infants at three days, three weeks, three months and six months of age.
Findings suggested factors before and at birth influence the development of the intestinal microbiota, and this in turn may influence the amount of body fat later in life. Researchers still can’t fully explain this relationship and further studies will be needed to delineate the mechanisms underlying these phenomena. However, the results provided further confirmation that components of the early gut microbiota are strongly influenced by environmental factors, even in healthy infants.
Future study and understanding could eventually lead to the development of nutritional products for expecting mothers, researchers suggested.
In January, Nestlé Health Science also completed a CHF 65.6 million investment in Seres Health Inc., Cambridge, MA, a microbiome therapeutics company that is developing a novel class of biological drugs designed to treat diseases by restoring the function of the microbiome.
“Hippocrates, considered the founder of modern medicine, was the first to consider the importance of the gut to overall wellness by suggesting that all disease began in the gut,” noted David Daguet, PhD, scientific manager at Nexira, Rouen, France.
One the most complex microbial ecosystems, the gut is “a diverse community of different bacteria types that play a vital role in fighting external factors that can negatively impact health, and play an instrumental role in maintaining health via the absorption of food and nutrients,” said Patrick Luchsinger, nutrition marketing manager, Ingredion Incorporated, Westchester, IL.
The most basic implication of a healthy gut on overall health and wellness is maintenance of normal nutritional status and effective absorption of food, water and minerals while fighting harmful foreign substances that enter the body through the gastrointestinal (GI) tract and easing their elimination, he said.
“Our knowledge of the resident species and their potential functional capacity is rapidly growing with each published paper,” Mr. Luchsinger added. “This impacts the nutraceutical ingredient market as it is furthering our understanding of the role of gut microbes, leading to science-driven new product development.”
Dr. Daguet emphasized the key role the microbiota plays in efficient nutrient absorption. “Through the process of fermentation, gut bacteria metabolize various nutritional substrates to end products. Under certain circumstances such as diet, medication, stress, age and general living conditions, the balance of the gut microbiota may be altered, leading to digestive discomfort like indigestion, irregular transit (diarrhea, constipation) or abdominal pain, to more serious conditions like irritable bowel syndrome (IBS), which afflicts nearly 30% of the U.S. population and 20% worldwide.”
About 60-70 million people suffer from digestive diseases in the U.S., according to the National Institutes of Health. Dr. John Deaton, vice president of technology, Deerland Enzymes, Kennesaw, GA, noted that, according to the American Gastroenterological Association (AGA) Institute, good digestive health describes appropriate nutrient absorption, intestinal motility, immune function and a balanced microbiota.
“Research over the past two decades has revealed that gut health is critical to overall wellness and immunity, and that an unhealthy gut contributes to a wide range of health challenges,” Dr. Deaton said. “I’ve seen the evidence of this in my own research, through clinical studies on our various products designed to support digestion. Our studies have shown that numerous health conditions beyond digestive discomfort can be affected when digestion is optimized with the aid of a dietary supplement—for example, reduced frequency of headaches or even general physical pain.”
Many researchers believe supporting digestive health and restoring the integrity of the intestinal barrier will be “one of the most important goals of health professionals in the 21st century,” Dr. Deaton added.
The digestive system is “ground zero” for many of the body’s vital functions, according to Michael Bush, senior vice president, Ganeden Biotech, Mayfield Heights, OH. “We all understand the role the gut plays in breaking down nutrients but there is growing evidence showing a link between gut health and the proper function of the immune system, reduction in inflammatory processes, mood regulation and metabolic processes.”
Research into understanding of gut bacteria has raised more questions, he added. “With over 10 times as many bacterial cells in the gut than make up the entire human body, we have to learn to live in harmony with our gut bacteria and nurture it to ensure that the microbiome is able to do its job unencumbered.”
Recent scientific discoveries have related to obesity, depression, stress, kidney health, cardiac health and a variety of other very specific areas, Mr. Bush noted. “In the not-so-distant future you may see food, beverage and supplement products coming to market with probiotic bacteria selected to address these specific areas.”
With a more dynamic understanding of the gut microflora ecosystem, new product development will expand into more symbiotic/synergistic products, such as functional foods and beverages that combine both probiotics and prebiotics, Mr. Luchsinger predicted.
However, the application has to make sense for the consumer. “Dairy (yogurt, dairy-based beverages) nutritional bars, healthy snacks and juices are good applications for functional foods because of the healthy connotation and association to gut health. Consumer acceptance will be much greater if these applications are further enhanced by probiotics, prebiotics or a combination of the two.”
The gut functions as the “front line of the body’s immune system,” said Dan Lifton, president, Maypro Industries, Purchase NY, noting 70% of the body’s immune cells reside in the gut. “The gut is also a communications center utilizing nerve cells to provide signals to the brain, which regulates hunger and controls weight gain. The gut is also responsible for the production of key hormones such as serotonin, which regulates mood, sleep and stress. The implication of these connections is that you cannot take care of your health without taking care of your gut. And on the flip side, many health problems can be addressed by addressing gut health.”
Each person’s gut bacteria profile is unique. However, understanding about characteristics of certain communities of bacteria may lead to development of novel personalized nutraceutical products, Mr. Lifton added. “I believe that the newly gained understanding of the gut microbiome has become the most compelling reason to pursue research in personalized medicine and to develop novel function-specific nutraceuticals.”
Dr. Daguet agreed, noting that understanding of the intestinal microbiota has increased significantly, “due to the recent developments in analytical techniques to analyze the composition of complex microbial ecosystems.”
“Several disorders have been associated with an altered composition of the gut bacteria,” he added. “As a consequence, the microbiota is increasingly recognized as a therapeutic target to improve health and wellness.”
For example, Faecalibacterium prausnitzii has recently been identified as an important gut bacterium that may be associated with Crohn’s Disease.
“For the nutraceuticals market, these findings open new growth opportunities,” Dr. Daguet said. “Gut health products could be able to target more consumers on a wide range of wellness applications such as cardiovascular, cognitive function, weight management, eczema, stress, etc. Recent studies have shown very interesting results in this field.”
Breaking Down Digestive Health
Sales of digestive remedies have grown 7% globally since 2008, reaching $15.7 billion in 2013, according to Euromonitor International. Market drivers include contemporary lifestyle trends (both healthy and unhealthy), aging populations and consumer awareness of digestive health conditions.
Dr. Daguet also noted that more consumers are connecting digestive health with general well-being. “Dietary fibers, prebiotics, probiotics or symbiotic dietary supplements, with more precise dosage and offering optimum comfort and tolerability are definitely highly relevant industry and consumer trends.”
Within the overall supplements market, natural ingredients with organic certification, clean label and being “naturally functional” are also major trends, he noted. “Fibregum from Nexira is an all-natural, organic and GMO-free source of 90% soluble dietary fiber coming from 100% natural acacia gum. Fibregum is recommended for clean label products and offers scientifically proven benefits. Clinical studies have demonstrated its numerous health benefits, including its action on digestive comfort and its prebiotic properties.”
Ingredion manufactures NutraFlora prebiotic fiber, a short chain fructooligosaccharide (scFOS). More than 34 human studies as well as numerous in vitro studies demonstrate the beneficial effects of scFOS on digestive and immune health, according to the Ingredion’s Mr. Luchsinger.
“NutraFlora’s short chain structure with glucose termination narrows the fermentation profile and while the good bacteria preferentially ferment NutraFlora scFOS, it does not allow for use by pathogens. Since pathogenic bacteria in the gut cannot ferment NutraFlora, it fosters an environment that favors competitive inhibition of pathogens. When Bifidobacteria species increase, pathogens tend to decrease in number.”
Nena Dockery, technical services manager for Stratum Nutrition, St. Charles, MO, said proper function of the digestive system is vital to overall health. “The digestive tract, beginning in the mouth, is the route through which all nutrients, critical for sustaining life and supporting optimal health, enter the body, are broken down into their readily absorbable forms, and enter into systemic circulation. The digestive tract also provides the means through which many harmful substances are prevented from entering the body’s systemic circulation.”
Two areas of digestive health that directly impact overall wellness include the efficiency of food breakdown and the condition of the intestinal wall, which includes the makeup of the gut microbiota.
“For food to be absorbed into circulation, it must first be broken down into components that are readily absorbed,” said Ms. Dockery. “This function is mainly performed by the action of gastric acid and digestive enzymes. If food is not sufficiently broken down in the stomach and upper small intestine, the most obvious repercussion is digestive distress, including cramping and bloating.”
“In addition, incomplete food breakdown limits nutrient absorption, which can ultimately impact the functioning of metabolic processes,” she continued. “In some individuals, undigested food can put stress on the intestinal wall, causing it to become more permeable to larger food fragments and even pathogens, allowing them to enter into circulation (a condition sometimes referred to as leaky gut syndrome). The presence of these fragments outside the digestive tract can lead to an immune system response, resulting in multiple ramifications in the body, including the development of food allergies and other autoimmune conditions.”
Better understanding of fiber types has led to improved product development, Ms. Dockery noted. “Kiwifruit contains both prebiotic fiber and a select group of polyphenolic compounds and has been shown to deliver both an effective and very gentle laxative effect.”
Stratum Nutrition offers a cold-pressed kiwifruit ingredient, ACTAZIN, which provides the benefits of premium New Zealand green kiwifruit in a powdered form. “ACTAZIN exhibits protein-digesting enzyme activity from its inherent actinidin content to help facilitate optimal protein digestion. The concentrated powder also contains more than 10% fiber in both soluble and insoluble forms. And it has been shown to exert an advantageous prebiotic benefit when combined with probiotics without promoting the growth of less desirable intestinal bacteria.”
Probiotics Proliferate
Substantial evidence has confirmed probiotic bacteria help support gut health. However, Ganeden’s Mr. Bush noted that benefits are specific to individual strains. “Ganeden’s patented strain, GanedenBC30 has been shown in multiple studies to support gut health through mechanisms such as gut pH lowering, bacteriocin production and helping provide an environment that is conducive to the growth of other native gut bacteria.”
Consumers are increasingly more health conscious, and they continue to look for convenient, great-tasting, lifestyle-friendly functional foods and beverages. “We have seen just the tip of the iceberg when it comes to innovation, and we believe the next few years will bring even more innovative applications and delivery systems centered around science-backed ingredients, driven by consumer demand.”
Probiotic-fortified food and beverage products for children, athletes, women and active seniors have gained popularity of late, Mr. Bush noted. “Consumers are no longer interested in taking another pill; they want to receive the benefits of probiotics while consuming something they already enjoy, and without having to adjust their daily routine. Products that offer more than one functional use—such as a probiotic-fortified sports nutrition shake that also supports digestive and immune health, or probiotic-fortified hot beverages such as tea and coffee that not only give the consumer their morning pick me up, but also their daily dose of probiotics—are trends where we have seen tremendous growth.”
Tim Gamble, president and CEO, Nutraceutix, Redmond, WA, agreed that a healthy digestive system is instrumental to overall wellness. “Clearly, if we are to gain benefits from dietary supplements and functional food ingredients, a properly functioning and highly capable digestive system are key. Due to the last few years of research, it is becoming widely recognized that gut health and a healthy, balanced gut microbiota, is related to a wide variety of systemic benefits, not just those traditionally associated with digestion.”
Education efforts have helped influence consumer awareness of probiotics, Mr. Gamble added, “along with continued investigation by researchers, health practitioners and quality conscious brands into, ‘What makes a good probiotic?’ This is the next logical step after what has been an introductory period characterized by the question, ‘What is a probiotic?’”
For more than two decades, Nutraceutix has been leading education efforts as a producer of natural probiotic organisms, and in recent years, with pioneering work on the proper delivery of live probiotics to the digestive tract. “This work, widely known as the assortment of BIO-tract delivery technologies, makes a wide variety of probiotics in dietary supplements better than ever, and is now recognized by over 30 patents worldwide, with many more patents pending.”
Probiotics are leading the gut health category, and for good reason: supporting research is convincing and the modes of action are clear, said Maypro’s Mr. Lifton.
“Maypro’s original bifidobacterium strain Morinaga BB536 is supported by more than 40 human clinical studies and works by supporting a healthy balance of bacteria in the GI tract and increasing short chain fatty acids. Maypro also distributes ProDURA—a spore-forming Bacillus coagulans strain clinically shown to assist in reducing total cholesterol levels and supporting the health of the vaginal and gastrointestinal tracts. When spores encounter the ideal conditions of temperature, moisture and pH in the large intestine, they revert to their active form.”
Gut health is really the basis for general good health, according to Michael Shahani, COO, Nebraska Cultures, Walnut Creek, CA, which manufactures ProDura. “It’s not only about absorption of nutrients but also how you keep out unhealthy bacteria.”
Overall, health has declined due to overconsumption of processed foods, over-prescription of antibiotics and other environmental stressors that can compromise the integrity of gut microbiota. “Having a healthy balance of good bacteria is really essential,” he said.
“Probioic bacteria are mostly what we call transient bacteria,” he noted. “We take them in through food or supplements, but they go away; they don’t live there forever. A certain amount does, but our bodies are designed to take nutrients in through food or fermented sources.”
While consumer awareness for specific probiotic strains has grown, along with demand for fortified foods and beverage, companies are challenged to deliver an efficacious dose at the time of consumption.
Mr. Shahani said Nebraska Culture’s ProDura brand offers good survivability at high temperatures for various products.
Companies also need to consider what type of probiotic foods consumers will pay a premium for, suggesting the health halo around dark chocolate has presented an interesting option for the probiotic market.
Overall, manufacturers of proprietary probiotic strains have made significant investments in clinical studies and major food companies have helped raise awareness of the benefits of probiotics, said Mr. Lifton. “However, the complexity of the probiotic ingredients and the sheer number of choices available have created challenges for the consumer. As a result, many brands moved to using high CFU (colony forming unit) counts as a point of differentiation, leading to what I call the battle of ‘millions, billions, trillions.’ Our strategy with the Morinaga BB536 strain was to focus on the availability of the clinical data and the stability at room temperature after two years, which enables brands to claim potency at date of expiry rather than date of manufacture. The stability story also applies to spore-forming probiotics such as ProDURA, which can be used in a variety of delivery forms, including gummies, beverages and foods.”
In terms of application format, probiotic-rich dairy products have already penetrated the market successfully, said Mr. Lifton. “We expect the category to continue its growth. However, consumer awareness of probiotics has reached such a level that you start to see digestive health ingredients in less obvious delivery forms. Kevita, for example, launched a line of sparking probiotic drinks that have strongly resonated with consumers. We expect those trends to continue as other innovative brands develop novel products in the category.”
In addition to its probiotic range, Maypro distributes Benegut, a patented extract of perilla leaf the company claimed has anti-spasmodic and anti-inflammatory properties clinically shown to reduce bloating.
Experts have identified the inheritance, composition, balance and health of the intestinal flora as major contributors to overall health and wellness, said Mike Petteruti, vice president, Gnosis USA Inc., Doylestown, PA, having direct implications for skin, cardiovascular, metabolic autoimmune disorders and even psychological conditions. “As a company, Gnosis has proven a commitment to performance-based nutritional products, and our BioOptima is our proprietary Saccharomyces boulardii product that has been shown to address the importance of gut flora composition and balance in humans.”
Safety, efficacy, consistency and stability are all important considerations, he added. “There are opportunities to examine benefits of combination products, but even before this, there is significant technical, manufacturing and clinical ‘innovation’ to be done to establish the reliability of currently promoted products.”
Mechanisms & Research
Certain probiotics are very effective in facilitating the digestive process through multiple mechanisms, including immune functioning and digestive enzyme production, according to Stratum’s Ms. Dockery. “Supplementing with probiotics or prebiotics that feed indigenous bacteria can be very therapeutic in improving gut health. It must be kept in mind that intestinal bacteria are particularly prone to the actions of antibiotics. Therefore, after a course of antibiotics, it is important to supplement with a probiotic and/or a prebiotic to restore the gut to homeostasis.”
Whole food sources have always been a preferential way to consume nutrients, she added, though they are not always as practical or convenient as supplements. “In some ways, functional foods and beverages can provide the best of both worlds. They are especially suited to gut health products such as fiber supplements that require more than a gram of active ingredient. High fiber food bars and clear liquid fiber beverages have enabled this often neglected nutrient to be consumed in ways that are much more palatable for many consumers.”
Since different strains offer specific benefits, Dr. Deaton said his customers are increasingly seeking a multi-strain formulation of both non-spore and spore-forming probiotics. “Based on this demand, more science is emerging to support the benefits of spore forming probiotic strains, such as Bacillus subtilis. Deerland Enzymes has genome sequenced for safety and clinically tested for efficacy DE111, a highly effective strain of Bacillus subtilis, a very stable probiotic spore that supports digestive health and works as a complement to many of the non-spore strains that are also available. The genome sequencing confirmed the strain contained no plasmids, antibiotic resistant or deleterious genes. The human clinical study showed the strain’s ability to control microbial populations, aid in digestion and maintain general health.”
In addition, research has shown certain prebiotics can increase the benefits of probiotics, he said. However, fiber-based prebiotics often come along with several drawbacks. “In response to this growing trend, Deerland Enzymes’ research and development team recently introduced a unique prebiotic that is not fiber or starch based, is highly effective in small doses (15 mg) and does not exhibit any of the drawbacks of more commonly used prebiotics. This patent-pending product, called PreforPro, is backed by a human clinical study, as well as both in vitro and in vivo studies that demonstrate its superiority to the typical prebiotics that have been used to date.”
Bérengère Feuz, marketing group manager, Lallemand Health Solutions, Montreal, Quebec, Canada, said technological advances in strain protection and fermentation processes have ensured more stable, heat- and acid-resistant probiotic yeast and bacteria, which enable innovative forms for increased convenience and versatility (e.g., liquids, powders, orodispersible sticks, chewables and products that no longer require refrigeration). “On the other side, scientific research has recently reached a new level with hundreds of high quality publications produced each year, and this also contributes to the reputation and success of the product category.”
Lallemand offers Lacidofil, a combination of Lactobacillus Rosell-52 and Lactobacillus Rosell-11. Both individual strains and their combination have been the subject of extensive research over the years. At least 23 human studies have been published to date, according to Ms. Feuz. “Lacidofil primary indications are in the area of gut health, with several positive studies in antibiotic-associated diarrhea prevention in children and adults, H. pylori eradication, acute gastroenteritis in children, management of IBS symptoms and lactose intolerance.”
The company’s Protecflor probiotic formula combines the synergistic activities of three well-documented Rosell bacteria strains with Saccharomyces boulardii probiotic yeast. Protecflor is recommended for reinforcing or restoring the intestinal barrier and for fighting intestinal infections, in particular traveller’s diarrhea, Ms. Feuz noted.
Additionally, a randomized, double-blind, placebo-controlled trial on daily intake of Bifidobacterium bifidum R0071 conducted at the University of Florida with 581 participants was published ahead of print by the British Journal of Nutrition. Research demonstrated a 45% reduction of the likelihood that a participant would report a cold/flu while on the probiotic compared to placebo.
The clinical study evaluated the individual effects of three probiotic strains—Bifidobacterium bifidum Rosell-71 (R0071), Bifidobacterium infantis Rosell-33 (R0033), Lactobacillus helveticus Rosell-52 (R0052), which are found in combination in the company’s ProbioKid formulation and have been previously shown to reduce the occurrence of common winter infections in school-aged children by 25% and absenteeism by 40%.
Enzyme Answers
Enzyme supplements continue to gain recognition among consumers, according to Deerland’s Dr. Deaton. “Bioavailability is a key consumer concern and the ability to breakdown food into its basic and useful components is of critical concern for consumers interested in functional nutrition for growth, development and supporting healthy aging.”
Digestive enzymes break down food-derived fats, carbohydrates and proteins into components the body can use. “During cooking and processing, the natural enzymes present in raw foods are denatured,” said Dr. Deaton. “In addition, our bodies don’t produce the enzyme cellulase at all; this is an enzyme that breaks down the cell wall of plants, releasing the nutrients for our bodies to absorb. Those who follow a vegetarian or vegan diet are likely missing out on key nutrients from the plant-based foods they’re eating, and would most certainly benefit from an enzyme supplement.”
Moreover, consumers are recognizing they may have difficulty with normal digestion of wheat and dairy. Eighteen million Americans believe they have difficulty digesting gluten, according to the Center for Celiac Research and Treatment. Meanwhile, 50 million people report discomfort due to ingestion of dairy products, according to the American Gastroenterological Association.
“To address the growing demand for products that address food sensitivities, Deerland Enzymes’ latest products Glutalytic and Dairylytic have been designed to optimize digestion of gluten and dairy proteins,” said Dr. Deaton. “These enzyme-based products hydrolyze wheat and dairy proteins and break them down into smaller constituents so they can be more easily managed by the body. Glutalytic helps minimize the unintended consequences of inadvertent gluten consumption, and is supported by a human clinical study. Dairylytic works to help break down not only the lactose associated with dairy foods, but also the proteins that can be difficult to digest and may cause discomfort to sensitive individuals. Fewer dietary restrictions can yield huge quality of life benefits.”
Bret Wyant, vice president of sales, American Laboratories, Inc., Omaha, NE, also acknowledged the importance of probiotics, prebiotics and enzymes, which can aid the digestion of proteins, carbohydrates and sugars to ease digestive discomfort or bloating symptoms that result from eating common foods and vegetables.
“American Laboratories promotes several functional enzymes for the ease of digestive discomfort that is found when consuming items like dairy and vegetables. We have found a large, growing interest in supplementing probiotic formulas with enzymes like alpha-galactosidase (digests fibers associated with beans/legumes), lactase (digests milk sugars for issues common to lactose sensitivity) and glyprozyme (functional enzyme blend for issues common to gluten sensitivity).”
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Packaged Facts predicted sales will exceed $2 billion in 2019. The gluten-free market is cementing its staying power as more than a mere dietary fad and continues to make national headlines, including a recent announcement by popular foodservice chain Pizza Hut that it will begin offering gluten-free pizza (in partnership with Udi’s). In the retail sector, sales of gluten-free foods posted an impressive compound annual growth rate (CAGR) of 34% over the five-year period ended in 2014, when market sales reached $973 million, according to a report from market research publisher Packaged Facts titled “Gluten-Free Foods in the U.S., 5th Edition.” “Retailers have embraced the gluten-free trend by stocking more gluten-free items, featuring them in store, and launching their own private label brands. In addition, retail chains have been courting the gluten-free consumer with a variety of festivals and events,” said Packaged Facts Research Director David Sprinkle. Packaged Facts’ July/August 2014 survey data revealed that more than a third of consumers claim gluten-free/wheat-free is an important factor when they are shopping for food. In addition, a quarter of survey respondents had purchased or used food products labeled gluten-free in the three months prior to the survey. Looking ahead, the gluten-free market’s momentum isn’t expected to wane any time soon. Packaged Facts projected sales will exceed $2 billion in 2019. The report highlighted several key factors favoring continued growth in the market, including:
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