Spurred on by significant media attention and industry education, the role of digestive health is increasingly being recognized by consumers and health practitioners as very important to overall well-being. The digestive tract is an intricate system that can be disrupted by disease, diet and emotional stress. Common digestive problems, such as heartburn and GERD (gastroesophageal reflux disease), inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) often result in symptoms that include bloating, diarrhea, gas, stomach pain and stomach cramps. Furthermore, a healthy digestive tract is critical in reducing the risk of autoimmune diseases, such as rheumatoid arthritis, lupus, scleroderma and multiple sclerosis.

The microflora of the human large intestine plays a very important role in overall digestive health. The intestinal microflora consists of at least 500 different bacterial species, which influence the conversion of (pro)carcinogenic substances, the production of vitamins, degradation of bile acids and digestion of nutrients. Certain microflora can have beneficial effects on gastroenteritis resistance, blood lipids, anti-tumor properties, lactose tolerance and gastrointestinal immunity. Of significance, the gut is the largest immune organ in the body. A hyper-stimulated immune system can lead to autoimmune problems, and a suppressed system can cause infection.

The number of publications about food- and supplement-based strategies to modulate the composition of the microflora and their associated beneficial effects has increased steadily over the last decade. Nutritional components, including probiotics and prebiotics, fiber and enzymes, are beneficial in ensuring a healthy digestive system through their effects on gut microflora, as well as gut immunity.

Probiotics, which literally means ìfor life,î are defined as ìlive microorganisms which, when administered in adequate amounts, confer a health benefit on the hostî1.

Lactobacillus (LAB) refers to a group of lactic acid-producing bacteria which make up many of the 400-plus normal probiotic species in the human body2. Lactobacilli provide many benefits, including:
* Inducing growth factors and increasing the bioavailability of minerals;
* Stabilizing the mucosal barrier and decreasing intestinal permeability;
* Inhibiting bacterial pathogens by producing lactic acid and hydrogen peroxide;
* Immunomodulating effects, such as stimulating immune function in healthy people, and down-regulating immune function in those with immune system hypersensitivity; and
* Inhibiting pathogenic bacteria.3,4

Bifidobacteria normally colonize in the human colon and, like Lactobacillus species, produce lactic acid. Bifidobacteria block bacterial infection in the gut, producing antimicrobial substances that are effective against many harmful gram-positive and gram-negative bacteria. Some species of Bifidobacteria (including B. infantis, B. breve and B. longum) bind to the intestinal mucosa and prevent attachment of pathogenic coliform bacteria5.

The Food and Agriculture Organization/World Health Organization (FAO/WHO) expert committee on probiotics proposed guidelines to assess probiotic microorganisms. They state prebiotic strains must be able to: 1) survive passage through the digestive tract containing gastric juice, bile and pancreatic juice; 2) must adhere to and grow within the intestinal mucosa; 3) be gram-positive organisms included in, but not necessarily limited to, the two genera, Lactobacillus and Bifidobacterium; 4) show a specific health benefit measured by defined tests (in vitro, animal and/or human); and 5) have defined dosage regimes and durations of use. Although not part of these guidelines, for food use, the probiotic products must have a good taste, smell and an acceptable shelflife.

Certain probiotics can help optimize the functioning of the bodyís immune system and strengthen its defenses by modulating the mucosal barrier of the gut, where approximately 70% of the immune system is located. Well-established probiotic effects are:
1. Prevention and/or reduction of duration and symptoms of rotavirus-induced or antibiotic-associated diarrhea, and lactose intolerance.
2. Reduction of the concentration of cancer-promoting enzymes and/or putrefactive (bacterial) metabolites in the gut.
3. Prevention and alleviation of unspecific problems of the gastrointestinal tract.
4. Beneficial effects on microbial irregularities, inflammation and other complaints associated with inflammatory diseases of the gastrointestinal tract, Helicobacter pylori infection or bacterial overgrowth.
5. Normalization of stool consistency and frequency in subjects suffering from irritable colon.
6. Prevention or alleviation of allergies and atopic diseases in infants.
7. Prevention of respiratory tract infections (common cold, influenza) and other infectious diseases, as well as treatment of urogenital infections6.
Preliminary evidence for probiotics also exists for hypocholesterolemic effects, improvement of the mouth flora and caries prevention, and reduction in autoimmune diseases (e.g., arthritis).

Purpose of Prebiotics
British researchers first reported certain dietary carbohydrates can promote the non-selective growth of gut bacteria and, hence, influence gut function7. Thus, the concept of prebiotics, which are typically defined as non-digestible substrates that can be selectively fermented by the gut microflora, arose8.

 For a food ingredient to be classified as a prebiotic, it must not be hydrolyzed or absorbed in the upper part of the gastrointestinal tract; be a selective substrate for one or a limited number of potentially beneficial bacteria in the colon, thus stimulating the bacteria to grow, become metabolically activated or both; and be able, as a consequence, to alter the colonic microflora toward a healthier composition9.

Prebiotics that have an influence on the diversity and metabolic activity of the microflora may consequently modulate the immune system. Each prebiotic component is unique and influences a specific component of the colonic microflora. Recent interest has focused on the positive effects of prebiotics on lipid and mineral metabolism, and in cancer prevention. For the most part, these effects are indirect, i.e., mediated by the intestinal microflora10.

The most common prebiotic ingredients include fructo¨-oligo¨sac¨charides (FOS), short-chain fructo-oligosaccharides, inulin, oligofructose, other indigestible oligosaccharides and derivatives from lactitol, which is a hydrogenated lactose. Dietary fibers also act as prebiotics, as they resist absorption in the small intestine and can be hydrolyzed and fermented (partial or total) by the bacteria in the large bowel11. Inulin and oligofructose show selective stimulation in the growth of beneficial gut flora, including lactobacilli and bifidobacteria12.

FOS occur naturally in a wide variety of plant foods, including onion, chicory, banana and artichoke, and are metabolized by intestinal microflora to form SCFAs, hydrogen, L-lactate and other metabolites. FOS (70% oligofructose and 30% inulin), administered for three weeks at a level of 15g, produced a significant improvement in disease scores, fecal Bifidobacteria count and gut immunological parameters on 10 active Crohnís disease patients13.

Resistant starch (RS) refers to starch and starch degradation products that are not absorbed in the small intestine, because they are resistant to the effects of the alpha-amylose enzyme. Because it is not effectively broken down in the gut, RS is considered to have similar physiological and health benefits as fiber, including prebiotic effects. The principle source of RS on the market is derived from corn starch.

The physiological effect of RS appears to be as substrate for colonic fermentation with a modest fecal bulking activity14. In this trial, the mean fecal butyrate:SCFA ratio, which has been suggested to have positive implications for colonic health, was significantly higher, following the consumption of RS. The increased butyrate produced may have implications for the luminal health of the enterocyte, with indirect improvements overall in the immune system.

The combination of FOS and RS results in a synergistic effect in the gut of rats with colitis, specifically increasing levels of lactobacilli and bifidobacteria in both the cecum and colon. The fibers also produced an upregulation of certain genes linked to improved intestinal barrier function15.

 Other fibers that are being studied as sources of prebiotics include psyllium and guar gum, rye flour, barley, orange juice waste stream, wheat-derived resistant starch, gum acacia and cereal-derived arabinoxylanoligosaccharides. Psyllium, for example, has been shown to be effective in maintaining remission in ulcerative colitis16. Pectic oligosaccharides derived from citrus processing reportedly reduce the adhesion of certain pathogens to intestinal cells17.

Probiotics and prebiotics can also be used in combination, a concept coined ìsymbioticî18. The live microbial additions (probiotics) act in conjunction with specific substrates (prebiotics) to im¨¨prove the survival of the probiotic organism, because its specific substrate is readily available for its fermentation. (See chart ìCommon Probiotics, Prebiotics and Synbiotics.î)

Enzymes for Digestion
More than 20 enzymes are responsible for digestion of nutrients, as well as their absorption, transportation, metabolism and elimination. Digestive enzymes include three classes: proteolytic or proteases are required to break down protein into amino acids; lipases which digest fat; and amylases needed to digest carbohydrates. Plant-, fungal- and animal-based materials are the most common sources of exogenous enzymes.

Enzyme supplementation is often used for digestive disorders, including exocrine pancreatic insufficiency and lactose intolerance. Pancreatic insufficiency is characterized by impaired digestion, malabsorption, nutrient deficiencies and abdominal discomfort19.

Proteases are important in alleviating tissue damage during inflammation. They act to enhance the breakdown of immune complexes formed between antibodies produced by the immune system and the compounds they bind to (antigens). Autoimmune diseases are associated with high levels of immune complexes in the blood. Excess levels of circulating immune complexes are also present in ulcerative colitis, Crohnís disease and AIDS20.

Proteolytic enzymes have a number of positive effects on the immune system, including enhancing the ability of immune cells to kill bacteria and viruses and stimulating the immune response by promoting formation of the anti-inflammatory compounds tumor necrosis factor (TNF-alpha), interleukin I-beta (IL-1b) and IL-621.

Understanding the normal microflora with regard to its metabolic activity and influence on the immune and endocrine systems remains a key area for future research. It is possible to manipulate the composition of the gut microflora through diet. Probiotics, prebiotics, and synbiotics and enzymes may contribute to nutritional modulation of the gut microflora, with beneficial effects on gastrointestinal health and immunity. NS

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