The Science of Digestive Health

“Things sweet to taste prove in digestion sour.”

            --William Shakespeare

Natural products catering to digestive health are positioned as the next big “thing”, as reports trickle in suggesting digestive health will dethrone heart health from the number one spot of top health concerns, especially as Americans report more digestive problems than ever before. National statistics confirm a rise in gastrointestinal (GI) problems; according to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 60 million to 70 million Americans are afflicted with digestive diseases. The cumulative effect includes 50 million physician visits and 10 million hospitalizations annually, with a direct and indirect cost on the economy of more than $107 billion.

“Currently in Western societies, the healthy intestinal flora of many people is compromised due to the modern diet, consumption of antibiotics and other prescribed or recreational drugs, smoking, and other factors such as stress and pollution,” said Michael Shahani, director of operations, Nebraska Cultures Inc. “As a result, many people have symptoms of poor digestion, gas, bloating, constipation and diarrhea.”

Increasing numbers of Americans are open to enhancing their digestive health with natural products. According to the Natural Marketing Institute (NMI), more than 15 percent are managing constipation, 14 percent irritable bowel syndrome (IBS) and 4.5 percent for stomach ulcer. NMI also found 20 percent of households turned to fiber and more than 10 percent used acidophilus probiotics in 2007.

What could be considered a renaissance or renewed interest in probiotics for digestive support is also driving interest toward other natural nutrients. Probiotics have garnered more mainstream acceptance, thanks in part to marketing campaigns from mega-brands entering the functional food category with items such as Danone’s Activia® yogurt and Yoplait’s Yo-Plus™. According to the technical research report, “The Probiotics Market: Ingredients, Supplements, Foods” from BBC Research, the global market for probiotic ingredients is on an upward swing. It is expected to be worth $15.9 billion in 2008 and reach $19.6 billion in 2013.

Its popularity can also be attributed to the growing amount of research suggesting probiotics can lower the risk or limit the progression of digestive ailments, including constipation and diarrhea, IBS, general intestinal viruses and antibiotic-associated infections. “A healthy population of gut flora (probiotics) has been proven as a requirement for good digestive health,” said Tim Gamble, vice president of sales and marketing, Nutraceutix. “Without it, the digestive tract struggles to assimilate nutrients and is more prone to digestive ailments and overgrowth of pathogenic bacteria. Many digestive disorders stem from a decreased population of healthy, natural probiotic organisms and the imbalance that occurs as a result.”

Hundreds of bacteria species reside in the human digestive tract gut; some are potentially pathogenic or putrefactive, and others are friendly. Beneficial bacteria, often known as probiotics, can be defined as live microorganisms in a supplement or food form that when administered in adequate amounts exert health effects on the host when consistently ingested.

Once a child is born, colonization of bacteria begins in the newborn’s intestines.¹Bfidobacterium infantis (B. infantis) and B. breve are the most predominant friendly bacteria in infants; however, proportions vary. For example, a breast-fed infant may have more Bifidobacterium and fewer Enterococci than formula-fed babies.² In a study from the University of Bari Policlinico, Bari, Italy, researchers studied the effects of probiotics on feeding tolerance, bowel habits and gastrointestinal motility in 30 preterm newborns. Ten were exclusively breast-fed, and the remaining 20 were given either Lactobacillus reuteri (L. reuteri) ATCC 55730 or placebo for 30 days. Children receiving probiotics showed a significant decrease in regurgitation and mean daily crying time and a larger number of stools compared to those given placebo. Gastric emptying rate was significantly increased and the fasting antral area was significantly reduced in both the newborns receiving L. reuteri and breast-fed newborns compared with placebo.³

Research in the area of children’s health and the use of probiotics is impressive: from improving the immune response of HIV-infected children,⁴ to its potential impact on children’s oral health,⁵ the use of probiotics in the prevention of atopic disease and the association between the disease and the composition of a child’s intestinal microbiota,⁶ its influence in asthma and respiratory conditions,⁷ and the potential for restoring the gut flora of autistic children.⁸ Supplementation with probiotics during a child’s early development has been found to also reduce the incidence of infections and diarrhea. In a double blind, randomized trial of children in day care, researchers examined whether long term consumption of a probiotic milk containing Lactobaciullus rhamnosus GG could reduce gastrointestinal and respiratory infections.⁹ Results indicated children in the Lactobacillus group had fewer absences because of illness; a slight reduction of severity and number of respiratory infections were also noted.

Probiotics used as a nutrient and treatment for acute infectious diarrhea in children continues to be studied. A meta-analysis of data from 1966 to 2000 showed a reduction in diarrhea duration of 0.7 days and a reduction in frequency of 1.6 stools on day two of treatment in participants who received Lactobacillus compared to those who received a placebo.¹⁰ The researchers concluded Lactobacillus is a safe and effective treatment for children with acute infectious diarrhea. From the Department of Pediatrics, University Carl-Gustav-Carus, Dresden, Germany, researchers tested the probiotic Escherichia coli (E. coli) Nissle 1917 (EcN) in infants with diarrhea in a double blind trial; they concluded EcN is a safe and well tolerated remedy for diarrhea occurring less than four days for children aged 1 to 47 months old.¹¹

A study out of the University of Naples Federico II compared the efficacy of five probiotic preparations: an oral rehydration solution (control group); Lactobacillus rhamnosus GG; Saccaromyces boulardii, Bacillus clausii; a mix of L. delbrueckii var bulglaricus, Streptococcus thermophilus, L. acidophilus and B. bifidum; or Entrerococcus faecium SF69.¹² The study mentioned that its preparations had already been tested but in different settings and end points^{13,14,15,16,17} and in other meta-analyses of probiotic efficacy and a Cochrane review,^18,19,20,21 but it aimed to offer additional feedback on the subject. The focus of the study was to identify the most effective preparations and whether the efficacy of probiotic preparations for the treatment of children with acute diarrhea was related to the strain of bacteria. The researchers found the median duration of diarrhea was significantly shorter in children who received L. rhamnosus strain GG or the four bacterial strains than in children who received the control. One day after the first probiotic administration, the number of stools was lower in children who received L. rhamnosus GG and in those who received the probiotic mix. The other preparations did not affect primary outcomes.

Antibiotics are commonly used to treat children with respiratory and skin infections, which can result in antibiotic-associated diarrhea (AAD). A systematic review published in The Cochrane Database Library noted between 11 and 40 percent of children suffer from AAD.²² Furthermore, the review analyzed 10 studies that tested 1,989 children who received antibiotics to treat a medical condition along with probiotics, such as Lactobacillus GG, Lactobacillus sporogenes, Streptococcus thermophilus and Saccaromyces boulardii, to prevent ADD. Results showed probiotics reduced the incidence of AAD. The reviewers concluded there was not sufficient evidence to advise physicians to recommend probiotics to prevent AAD routinely; however, Lactobacillus GG or Saccaromyces boluardii appear to be the most effective.

Feeding the Flora

Depending on genetic makeup, dietary habits, age, medications, stress levels and physiological conditions, the composition of intestinal microflora will vary from person to person.

Probiotics continue to lead the pack when it comes to proactive nutraceutical treatments; they are ideal for individuals who consume little fiber or fermented foods, are taking antibiotics, have repeated intestinal or vaginal infections or travel frequently, according to Peilin Guo, M.S., R.D., vice president of Functional Foods, Clinical Research and Asian Market Development Research, Jarrow Formulas. Probiotics have been well researched and heavily advertised, and their major functions are metabolic activities that salvage nutrients, support immune health and protect the body against pathogenic microbes. A review published in the Journal of Applied Microbiology suggested probiotics play an important role in a healthy diet and provide a safe, cost effective and natural approach that adds a barrier against microbial infection.²³

The role of probiotics in the management of IBS is well documented; however, the etiology and pathophysiology of the disease is poorly understood, according to a review from the University of Alberta that discusses the evidence from trials and the mechanisms of action of probiotics as they apply to IBS.²⁴ Another study from S. Raffaele University Hospital, Milan, Italy, noted data on probiotics for IBS is still limited and contradictory since trials have been performed using different species, dosages, treatment durations and end-points for results evaluation.²⁵ An analysis of randomized controlled trials evaluating probiotics for IBS found B. infantis 35624 (Bifantis®, from Proctor&Gamble), an ingredient in A Lign®, was one probiotic to demonstrate improvement in IBS symptoms based upon the reviews study design.²⁶

A review of IBS and therapeutic approaches suggested treatment options are rapidly evolving beyond traditional symptom-based therapies toward agents with organ-specific receptors selectively directed at specific gastrointestinal functions.²⁷ Another meta-analysis on the efficacy of probiotics in IBS found these nutrients improve symptoms of IBS and can be used as a supplement to standard therapy.²⁸

Individual strains continue to be researched and evaluated for possible synergistic effects in the treatment of IBS. Researchers at the M. Curie Regional Hospital assessed the efficacy of Lactobacillus plantarum 299V (LP299V) in patients with IBS.²⁹ After four weeks, the patients who received the probiotic said their abdominal pain was resolved; a trend toward normalization of stool frequency in constipated patients was also noted in six out of 10 patients who received the probiotic. With regard to all IBS symptoms, an improvement was noted in 95 percent of the 20 patients who received LP299V vs. 15 percent of the patients who received the placebo.

A study from the University of College Cork, Cork, Ireland, aimed to compare the response of symptoms and cytokine ratios in IBS with ingestion of probiotic preparations containing either Lactobacillus salivarius UCC4331 or B. infantis 35624.³⁰ For eight weeks, 77 subjects with IBS drank a malted drink with a dose of 1 X 10¹⁰ live bacterial culture cells or a placebo drink. For all IBS symptoms, with the exception of bowel movement frequency and consistency, those randomized to B. infantis 35624 experienced a greater reduction in symptom scores, composite and individual scores with abdominal pain/discomfort, bloating, and bowel movement difficulty were lower than for placebo. A study from the University of Manchester, England, also focused on B. infantis 35624 as a nutrient to relieve certain IBS symptoms in women at a dosage level of 1 X 10⁸ colony forming units (cfu) and delivered in a capsule.³¹ The researchers concluded that the specific probiotic dosage delivered in a capsule could relieve many IBS symptoms.

Stress plays an important role in the initiation and exacerbation of bowel and discomfort symptoms contributing to IBS. A study out of the University of Washington showed a link and correlation between stress and IBS symptoms in women.³² The researchers found psychological distress moderated the effect of stress on GI symptoms, suggesting treatment protocols that incorporate strategies to decrease stress and psychological distress are likely to reduce GI symptoms.

A double blind, placebo-controlled, randomized study investigated the effects of a probiotic preparation (Probio-Stick®, from Institut Rosell Lallemand SAS) containing Lactobacillus acidophilus Rosell-52 and Bifidobacterium longum Rosell-175 on stress-induced symptoms in volunteers.³³ After three weeks, the consumption of probiotics significantly reduced two stress-induced gastrointestinal symptoms (abdominal pain and nausea/vomiting) but did not significantly modify other physical and psychological symptoms and sleep problems associated with stress. The researchers concluded Probio-Stick could provide a beneficial effect on GI symptoms by individuals affected by chronic stress.

Chronic psychological stress, including water avoidance stress (WAS), induces intestinal mucosal barrier dysfunction and impairs mucosal defenses against luminal bacteria. Lactobacillus helveticus and L. rhamnosus in drinking water was given to rats before they were exposed to WAS or sham stress for 10 days.³⁴ The findings from the study indicated probiotics could prevent chronic stress-induced intestinal abnormalities and thereby exert beneficial effects in the intestinal tract.

Multi-species probiotics are also being considered for easing IBS symptoms. A study from the University of Helsinki, Finland investigated the effects of multi-species probiotic supplementation (L. rhamnosus GG, L. rhamnosus Lc705, Propionibacteriumfreudenreichii ssp.Shermanii JS and Bifidobacterium animaliss ssp. Lactis Bb12) on abdominal symptoms, quality of life, intestinal microbiota and inflammatory markers in IBS.³⁵ For five months, 86 IBS patients (Rome II criteria) were randomized to receive either the multi-species probiotic or placebo daily; the results indicated the IBS score decreased 14 points from baseline with the probiotic vs. three points from the placebo.

“Probiotics can provide substantial protection against traveler’s diarrhea, most often related to ingestion of pathogens to which our bodies are unaccustomed,” wrote S.K. Dash, Ph.D., in “A Consumer’s Guide to Probiotics.” In a study published in his book, DDS® probiotics from UAS Laboratories were given to subjects one week before the travel, which markedly reduced incidence of traveler’s diarrhea (TD), with only three of eight individuals coming down with TD.³⁶

Another set of researchers looked at the effect of different probiotic formulations on the travelers’ diarrhea model in rats: five groups of six rats were given either a placebo saline, a suspension of probiotics (Lactobacillus-Rosell 11, Lactobacillus-Rosell 52 and Bifodobacterium-Rosell 175), a yeast probiotic (Saccharomyces boulardii), or a combination of both (Protecflor®, from Institut Rosell-Lallemand).³⁷ All the probiotic groups had improvements in symptoms; but, the combination product appeared to be most efficient.

Several studies have suggested certain probiotics such as L. acidophilus do not prevent TD.³⁸ A meta-analysis from the Veterans Affairs Puget Sound Health Care System looked into the controversy and attempted to compare the efficacy of probiotics for the prevention of TD in published randomized, controlled clinical trials.³⁹ Twelve of the 940 studies (from 1977 to 2005) met the criteria; from these, researchers concluded several probiotics, including Saccaromyces boulardii and a mixture of L. acidophilus and Bifidobacterium bifidum, had significant efficacy.

AAD also plagues adults and is a common complication of antibiotics and Clostridium difficile disease (CDD). The use of probiotics for the prevention of AAD and the treatment of CDD was evaluated in a meta-analysis.⁴⁰ Of the 180 screened studies, 31 fit the criteria and demonstrated that a variety of probiotics (Saccaromyces boulardii, L. rhamnosus GG and probiotic mixtures) can significantly reduce the risk of AAD and posses significant efficacy for CDD.

Developments in Probiotics

New research in the field of probiotics continues to unfold great opportunities. For example, researchers at University College London found Lactobacillus casei Shirota may restore the immune function of white blood cells in alcoholics.⁴¹ A yogurt fermented with Lactobacillus delbruekii var bulgaricus and Streptococcus thermophilus was supplemented with L. rhamnosus GR-1 and L. reuteri RC-14 can ease the suffering of diarrhea and nausea in individuals with HIV and AIDS.⁴² On the heels of a report that L. rhamnosus reduced the duration of gastrointestinal symptoms in marathon runners,⁴³ another study found Lactobacillus fermentum may boost immune health and protect long distance runners from respiratory illnesses.⁴⁴ In a pilot study, daily ingestion of a delayed release, four-species probiotic supplement (Immunobiotix®, from Nutraceutix) over an eight-week period could enhance innate immune function.⁴⁵

“Probiotics are hot, and not just for digestive health,” said Gamble. “There is a wealth of research, both past and present on the digestive health benefits of probiotics; however, there is increasing evidence and interest in the system benefits of probiotic supplementation particularly in the area of immune system stimulation and weight loss.”

Henri Durand, R&D director, Institut Rosell-Lallemand, added the future holds promise for new probiotic innovation and findings. “Strain selection is evolving, thanks to the advent of molecular genetic-based technologies we now have a different approach for strain selection and identification,” he said. “By applying genomic and metabolomic studies at both bacterial and host cells level, we are able to analyze precisely the properties and function of a probiotic strain, as well as their potential effects on gut epithelium, for example, and select the best strains. Thanks to the predictive power of these tools we are moving from a trial and error selection strategy toward rational strain selection.”

Bolstering the Effects

Prebiotics have a key role to play in the digestive arena, serving as a natural food for probiotic bacteria, thus supporting their growth. “Probiotics are live bacteria that confer a benefit when consumed in sufficient quantities,” Shahani said. “Prebiotics are substances, primarily certain kinds of carbohydrates that act as a stimulus or ‘fertilizer’ for the probiotic bacteria.”

Researchers from the Dundee University Gut Group reviewed published evidence for prebiotic effect on gut function and human health.⁴⁶ They found three prebiotics—oligofructose, galacto-oligosaccarides and lactulose—alter the balance of the large bowel microbiota by increasing bifidobacteria and Lactobacillus numbers.

Regularly consuming short-chain fructooligosaccarides (sc-FOS, as NutraFlora® from GTC Nutrition) was found to improve digestive comfort in a working population not undergoing medical treatment in a comparative double blind trial with 2,235 subjects.⁴⁷

Supplementation with the prebiotics inulin and oligofructose may extend one’s life by more than 30 percent, according to a study that evaluated male and female rats fed a prebiotic-containing diet.⁴⁸ The researchers also noted the animals had lower body weight, cholesterol and plasma triglycerides compared to rats fed the control diet.

A synbiotic product contains both a probiotic and a prebiotic ingredient. “Combinations of prebiotics with probiotics offer better opportunities for the probiotic bacteria to grow,” noted Dash. “They can then multiply faster in the gastrointestinal tract as prebiotics selectively feed probiotics. Since yeast and pathogenic cultures are absent, and the probiotic product has its own supply of prebiotics, this is an excellent choice for yeast sufferers.”

In a randomized, double blind crossover trial, 53 adults were randomly assigned to receive either daily supplements of placebo or oligofructose (Orafti P95, 6.6 g/d) and probiotics (Lactobacillus fermentum Me-3, Lactobacillus paracasei 8700:2 and Bifidobacterium longum 46) for three weeks.⁴⁹ The researchers reported total antioxidant activity in subjects receiving the synbiotic product was higher than the placebo: 42.4 vs. 41.9 percent. Additionally, levels of oxidized low-density lipoprotein (LDL) cholesterol were reduced, suggesting a combination product could reduce levels of biomarkers linked to oxidative stress.

“The combination of probiotics and prebiotics is promising,” Gamble said. “Reviewing the current literature, it would seem that supplementation with probiotics and prebiotics is best done in two steps. First, supplement with quality probiotics to establish intestinal balance and reduce the presence of pathogenic bacteria. Then, if desired, a prebiotic can be added to a regimen.”

Enhancing the GI

“As consumers are being forced to better understand the role of their digestive system, they are being asked to address areas of poor digestion and inadequate intestinal health,” said Lisa Clark, director of sales, business development, Deerland Enzymes. “Probiotics are becoming more mainstream in foods, which opens up additional exploration into supplemental enzymes, too.”

The human body produces more than 20 digestive enzymes in various organs and glands. The stomach glands produce gastric enzymes, including peptidase (for proteins), gelatinase (for gelatin/collagen from meats) and gastric lipase (for tributyrin, a butter fat). Meanwhile, the pancreas is responsible for secreting numerous proteases and amylases, including trypsin (a peptidase), pancreatic amylase (for starch and glycogen) and several elastases (for protein elastin). Then, the epithelium in the small intestines creates many peptidases and the more well-known amalyases that break disaccarides into monsaccarides—sucrase for sucrose and glucose, lactase for lactose, and maltase for maltose.

Vegetables and fruits also offers vital enzymes needed to digest foods. For instance, pectinase from the cell walls of plants helps degrade pectin. Enzymes from bacteria are also beneficial for digesting food—phytase helps denature phytic acid found in grains and seeds; cellulose breaks down the indigestible fibers found in plant cell walls.

“Enzymes are integral to the digestive process,” said Nena Dockery, technical resources manger, National Enzyme Co. “If the necessary enzymes for digestion are not present, the whole body experiences the results ranging from simple discomfort to excruciating pain, constipation, diarrhea, poor nutrient utilization, disruptions in the immune system functioning and a lack of energy.”

Pancreatic enzyme supplementation has been used for conditions such as pancreatic insufficiency and cystic fibrosis, in which the availability of pancreatic enzymes is decreased dramatically or absent altogether. Supplementing with such enzymes can help break down food when the body’s own digestive mechanism cannot. Additionally, enzymes can help with one of the most common digestive ailments, lactose intolerance. The digestive enzyme lactase has been shown to eliminate the symptoms of lactose intolerance by replacing the missing enzyme.⁵⁰ Dockery noted supplementing with the intestinal digestive enzyme alpha-galactosidase can provide a great benefit in alleviating symptoms commonly experienced after eating foods such as legumes and grains containing raffinose, stachyose or verbascose sugars.

Enzymes continue to be a burgeoning area for research, especially with greater awareness that enzyme deficiencies may be a factor in digestive ailments;⁵¹ however, most of the current research involves the use of enteric-coated pancreatic enzyme supplements.⁵² This has piqued interest in research examining non-animal sources, such as microbial and plant enzymes for digestive support.

“The incidence of digestive disorders ranging from recurrent heartburn to Crohn’s disease continues to grow dramatically, indicating the need for enzyme supplements to help ameliorate some of the symptoms of these disorders will continue to be a growing need within the dietary supplement industry,” Dockery said. “The use of digestive enzymes to help manage specific digestive disorders, such as non-celiac gluten sensitivity is currently being actively researched. As more information is uncovered about the causes of various digestive disorders, the greater likelihood there will be enzyme deficiencies in many of these disorders.”

Clark added word-of-mouth campaigns are helping to shed light on the category and the benefits enzymes have on digestive health. “Consumers are starting to hear more on the use of enzymes in drug development for various diseases,” she said. “Even though these enzymes do not relate to nutritional supplemental use of enzymes, just hearing the word in mainstream media gives more validity to the category. Beyond digestion, enzymes are also being taken, with success, away from meals to help with detoxification, circulatory issues, inflammatory conditions, and other systemic health problems potentially caused by circulating undigested proteins.”

As individuals attempt to ease their digestive woes naturally, supplements such as probiotics, prebiotics and enzymes are the latest candidates to be studied and researched for their ability to establish and maintain a healthy digestive system. But the role of natural nutrients and digestive health doesn’t just end here. In fact, one can say the category is just blossoming, and many more discoveries are waiting on the horizon.

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Editor's note: References start on the next page.

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