The role of functional foods in promoting gut health

The role of functional foods in promoting gut health

No health claims have been accepted so far for gut health in the US, but several nutrients already are used in clinical work and also marketed to consumers. Raija Tahvonen, PhD, and Seppo Salminen assess the state of the science

Perhaps the best-known group of functional foods for gut health is probiotics, which are considered to maintain or improve gut health via several mechanisms: They maintain a barrier against colonisation by pathogenic bacteria, inhibit the growth of pathogens and enhance the gut immune response by contact and crosstalk with the host via the mucosa.

The human gut is defined either as the lower part of the alimentary canal — the intestinal tract or the entire gastrointestinal tract: mouth, oesophagus, stomach, small intestine (duodenum, jejunum, ileum), large intestine and rectum. The gastrointestinal tract (GI) is designed to comminute and digest food, and to absorb and secrete nutrients and other compounds, including toxic immunological challenge and transient mechanical challenge. To ensure normal function, the gut with its microbiota forms the largest sensory, endocrine and immunological organ of the body.

Different probiotics show different effects (See Table 1). Probiotics colonise the gut temporarily and they must be consumed regularly.1 The effects of probiotics can be enhanced by simultaneously providing prebiotics.

Gastrointestinal epithelial cells especially are affected by nutrient intake
Chemical modification of starch and other cereal components and inulin offers possibilities for modifying their digestibility and thus efficiency as prebiotics. 2,3,4 In addition, the combination of long-chain polyunsaturated fatty acids and probiotics could offer significant protection against atopy. 5

Diet may affect the composition and activity of the gut microbiota. Breast-fed infants have a microbiota consisting mainly of bifidobacteria, while formula-fed infants have more complex microbiota similar to that of adults.6 During and after weaning, the microbiota of both breast- and formula-fed infants still develop and become more complex than during breast-feeding.

Fermentable dietary fibre is an important source of energy for gut microbes. In the basic fermentation, poly-, oligo- and disaccharides are hydrolised to the constituent sugars. Fermenting yields short-chain fatty acids, mainly acetate, propionate and butyrate, and gases such as CO2, CH4 and H2, and increases biomass.2 Short-chain fatty acids also lower pH in the intestines and are therefore believed to prevent the overgrowth of pH-sensitive pathogenic bacteria. Because polyunsatured fatty acids (PUFAs) are also antimicrobials, they may affect commensal microbiota.

Specific dietary PUFAs might be used to antagonise potential pathogens and/or encourage health-promoting lactic acid bacteria.7

Gastrointestinal epithelial cells especially, but also other cells such as M-cells, enteroendocrine cells, intraepithelial lymphocytes and the multiple cell types of lamina propria, are all affected by nutrient intake. Many nutrients play an important role in the maintenance of normal mucosal function in the gut area.8 Age-related changes also could influence nutrient utilization and especially microbiota on the mucosa. Thus, the intestinal microbiota becomes less complex during ageing and the metabolic role of the intestinal microbiota is altered. This may result in poorer utilization of nutrients and reduced detoxification of harmful components in the gut as well as increased risk for intestinal infections.9,10,11

Proteins and amino acids
The gut uses a large proportion of the total protein intake and is responsible for the main part of the first-pass metabolism of dietary amino acids. The gut also uses arterial essential amino acids, but so far very little is known about the nature of the amino acid transporters on the basolateral membrane of the enterocytes. Intestinal tissues, especially small intestinal mucosa, synthesise proteins at a high rate. Most of these proteins are secretory proteins, which are at least partly recycled to the body. The gut utilizes glutamine, aspartate, glycine and glutamate also for the biosynthesis of nucleotides, glutathione, polyamines, and nonessential amino acids, and for energy. The gut regulates actively the flow of amino acids from the diet to the body, perhaps by systemic hormones or by gut regulatory peptides. The gut seems to remove the amino acids necessary for its own integrity and physiologic function.12

Children with mild vitamin A deficiency are at increased risk of diarrhoea, and vitamin A supplementation decreases mortality
Glutamine is an important fuel source for cells rapidly turning over, such as epithelial cells, lymphocytes, fibroblasts and reticulocytes. It is a nonessential amino acid under normal conditions. Several in vitro and in vivo studies show an important role for glutamine in the maintenance and repair of gut mucosa in critically ill patients and it may be a conditionally essential nutrient. More studies are, however, needed on its effects on intestinal permeability, bacterial translocation and small-bowel histology. 8

Glutamate is another amino acid playing an important role as an enterocyte energy source but also elsewhere in intestinal physiology and metabolism. Glutamate has a part in intestinal growth, repair and function, including stimulation of cell proliferation and epithelial cell migration, enhanced growth factor signalling, upregulation of mucosal cell glutathione production and heat-shock proteins and effects on the immune system.13

Arginine is also considered to be a non-essential amino acid, but like glutamine it may be essential during catabolic states such as trauma and sepsis. Arginine is a precursor for nitric acid (NO). NO may have both anti- and proinflammatory effects and excessive NO production has been found in endotoxemia, septic shock, and increased intestinal vascular permeability. Arginine-containing formulas seem to reduce infectious complications in some surgical patients. The benefits to other patient groups need further studies.8,13 Dietary or luminal glycine and histidine may have protective effects on gastrointestinal tissues, and studies on their usefulness in diarrhoeal illness are currently being undertaken.13

Vitamins and minerals
Vitamin A is important for epithelial cell integrity and immune function. In animal experiments, vitamin A deficiency leads to reduced epithelial cell renewal and when paired with other inflammatory or infectious conditions results in significant histologic abnormalities. Infants and children with mild vitamin A deficiency are at increased risk of diarrhoea, and vitamin A supplementation seems to decrease mortality. However, it has not been proved whether vitamin A is protective also when its intake is adequate and in other population groups.8

Zinc is needed in protein synthesis and transcription proteins and it is thus important to cells with a high rate of turnover. Zinc supplementation has been shown to be beneficial in the treatment of diarrhoea in children whose zinc intake may be marginal and/or phytate intake high. Current clinical studies seek to identify other patient populations whose dietary zinc intakes are higher than expected.8

Deficiencies of several specific nutrients inhibit the growth and turnover of the intestinal mucosa.13 However, more clinical studies are needed to prove the usefulness of supplementation with doses higher than the present recommendations.

Dietary fibre
Dietary fibres promote beneficial physiological effects, including laxation (faecal bulking and softening, increased frequency), and regulate bowel movements. Dietary fibre consists of several different groups of molecules with different effects. Insoluble fibre especially contributes to laxation and normal bowel function, but fermentable/soluble fibre promotes faecal bulking through fermentation and microbial growth.2

Gut microbes ferment part of the fibre to short-chain fatty acids (SCFA). The concentration of SCFA produced varies depending on substrates, commensal microbes and site of fermentation. Assessing fermentation and SCFA production in humans so far is complicated. Anyway, SCFA seems to be beneficial to gut health via several actions. Colonocytes absorb and metabolise SCFA, which are major respiratory fuels and trophic to the small bowel and colon.2

Plant phenolics
Plant phenolic compounds only recently have been considered nutritionally important. Two large groups — flavonoids and phytoestrogens especially — have raised interest. Flavonoids are effective antioxidants due to their phenolic hydroxyl groups, but they have many other beneficial effects such as anti-inflammatory and anticarcinogenic activities. Gut microbes metabolise phytoestrogens to biologically active mammalian compounds with weak oestrogen activity.

Like flavonoids, phytoestrogens are also antioxidants and have anticarcinogenic and antimicrobial properties.14 Thus the microbiota may have profound health effects, especially on the mucosa.

These plant phenolics may selectively affect growth of intestinal microbes, thus influencing the bacterial population dynamics. Plant phenolic from olives, tea, wine and berries have antimicrobial properties.14 The effects of phenolics on gastrointestinal microbiota are poorly understood. The gut microbes metabolise phenolic compounds, and the metabolites can affect the epithelium and the colonic microbiota. Absorbed metabolites are found in plasma and urine and may have systemic health effects.14 Elevated enterolactone levels in urine and in serum are thought to be related to the activity and composition of colonic microbiota. Increased use of fibre and plant foods raises serum enterolactone concentrations in animal studies and high levels have been reported in human subjects consuming large amounts of whole-grain cereals, fruit and vegetables. The use of antibiotics decreases enterolactone concentrations; therefore, it is likely that the intestinal microbiota has a role in enterolactone production.15

Raija Tahvonen, PhD, and Professor Seppo Salminen work in the department of biochemistry and food chemistry at the University of Turku, Finland.
Excerpted from Functional foods, ageing and degenerative disease, C. Remacle and B. Reusens, editors. ISBN 0-8493-2538-2. Published by Woodhead Publishing Ltd, England.
www.woodheadpublishing.com
Respond: [email protected]

References
1. Calder PC, Kew S. The immune system: a target for functional foods? Brit J Nutr 2002; 88:S165-S176.
2. Topping DL, Clifton PM. Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol Rew 2001; 81(3):1031-64.
3. Charalampopoulos D, et al. Application of cereals and cereal components in functional foods: a review. Int J Food Microbiol 2002; 79:131-41.
4. Stevens CV, et al. Chemical modification of inulin, a valuable renewable resource, and its industrial applications. Biomacromolecues 2001; 2:1-16.
5. Das UN. Essential fatty acids as possible enhancers of the beneficial actions of probiotics. Nutrition 2002; 18:786-9.
6. Harmsen HJ, et al. Analysis of intestinal flora development in breast-fed and formula-fed infants by using molecular identification and detection methods. J Pediatr Gastroneterol Nutr 2000; 30(1):61-7.
7. Donnet-Hughes A, et al. The intestinal mucosa as a target for dietary polyunsaturated fatty acids. Lipids 2002; 36:1043-52.
8. Duggan C, et al. Protective nutrients and functional foods for the gastrointestinal tract. Am J Clin Nutr 2002; 74:789-808.
9. Benno Y, Mitsuoka T. Development of intestinal microflora in humans and animals. Bifidobacteria Microflora 1986; 5:13-25.
10. Hopkins M, et al. Age- and disease-related changes in intestinal bacterial populations assesssed by cell structure, 16S rRNA abundance, and community cellular fatty acid profiles. Gut 2001; 48:198-205.
11. Hebuterne X. Gut changes attributed to ageing: effects on intestinal microflora. Curr Opin Clin Nutr Metab Care 2003; 6:49-54.
12. Reesd PJ, Burrin DG. The gut and amino acid homeostasis. Nutrition 2002; ?16(7/8):666-8.
13. Ziegler TR, et al. Trophic and cytoprotective nutrition for intestinal adaptation, mucosal repair, and barrier function. Ann Rev Nutr 2003; 23:229-61.
14. Puupponen-Pimia R, et al. Development of functional ingredients for gut health. Trends Food Sci Technol 2002; ?13:3-11.
15. Kilkkinen A, et al. Use of oral antimicrobials decreases serum enterolactone concentration. Am J Epidemiol 2002; 155:472-7.

Probiotic bacteria and their reported effects in human studies

Strain

Reported effects in clinical studies

L. johnsonii LA1

Adheres to human intestinal cells, balances intestinal microbiota, enhances immunity (adjuvant in H. pylori treatment.)1,2,3,4

L. acidophilus

Lowers faecal enzyme activity, decreases faecal mutagenicity, prevents radiotherapy-related diarrhoea.3

NCFB 1748
L. casei Shirota

Prevents intestinal disturbances, balances intestinal bacteria, lowers faecal enzyme activities, positively affects reducing the recurrence of superficial bladder cancer.1,4,5,6

S. thermophilus
L bulgaricus

No effect on rotavirus diarrhoea, no immune-enhancing effect during rotavirus diarrhoea, no effect on faecal enzymes, strain-dependent improvement of lactose intolerance symptoms.3,4

L acidophilus
La-5

Balances intestinal microbiota, protects against traveller's diarrhoea, enhancemes immune system.3,4

B. Lactis Bb-12

Treats viral diarrhoea including rotavirus diarrhoea, alleviates symptoms of food allergy, balances intestinal microbiota.1,6,7

L. reuteri

Shortens rotavirus diarrhoea, colonising the intestinal tract.3,4,8

S. boulardii

Prevents antibiotic-associated diarrhoea, treats C. difficile colitis.2

Probiotic mix
VSL 3
(L. bulgaricus,
L. plantarum,
S. thermophilus,
B. longum,
B. infantis,B. breve)

Positive effect in inflammatory bowel disease and irritable bowel syndrome; treatment and prevention of pouchitis, prevention and alleviation of radiotherapy-associated diarrhoea.9,10


The $23-billion US gastrointestinal health products market in 2004


Resistant starch: the benefits of fibre … and more

The positive benefits of fibre on human health are well documented. Resistant starch is a form of fibre that delivers all the benefits of fibre. But it can go much further than that. High amylose corn resistant starch offers four main advantages over other fibre fortification options such as bran, cellulose and inulin.

  1. It offers well-studied health benefits, including intestinal/colonic health and metabolic benefits in glycaemic management and energy. Other non- or less-fermentable fibres such as wheat bran and cellulose cannot match these benefits because the benefits stem from resistant starch's fermentation in the large intestine.
  2. It is 'invisible' in foods, meaning it doesn't affect taste and texture like other insoluble fibre sources often do.
  3. It is especially appropriate for grain-based low- and moderate-moisture foods. It is commonly used for flour replacement. Its physical properties, particularly its low water-holding capacity, provides good food processing characteristics and desirable textural attributes (such as crispness and expansion) when compared to foods of similar fibre content.
  4. Because of the slow fermentation characteristic of resistant starch's insoluble structure, it can be consumed at significantly higher quantities without the digestive side effects common to soluble fibres such as inulin and fructo-oligosaccharides.

Consumption of foods containing natural resistant starch positively affects digestive health by:

  1. Promoting regularity with a mild laxative effect.
  2. Selectively increasing beneficial bacteria — what's called a 'prebiotic' fiber.1
  3. Increasing short-chain fatty acids in the colon. Particularly important for colon health is butyrate, which is the primary energy source for colon cells. Butyrate has anticarcinogenic and antiinflammatory properties that are important for keeping colon cells healthy.2,3 A study published in the journal Cancer Biology & Therapy in March 2006 points to high amylose corn starch as a carbohydrate that may help to prevent colonic DNA damage in people who consume high levels of protein — particularly cooked red meat. The study, conducted by Commonwealth Scientific and Industrial Research Organization Health Sciences in Australia, shows that the addition of natural high amylose corn resistant starch to the diet of rats prevented colonic DNA damage caused by a high-protein diet. It also prevented the thinning of the protective mucous layer. Because colonic DNA damage is an early step in the initiation of cancer, these findings suggest that including a resistant form of starch made from high amylose corn may help to reduce the risk of colon cancer.4
  4. Reducing intestinal pH and the production of potentially harmful secondary bile acids, ammonia and phenols.5
  5. Preventing the degradation of the mucous layer within the large intestine, which is believed to protect colon cells.
  6. Protecting colon cells from DNA damage; promoting the normalisation (ie, differentiation) of cancerous cells within the colon; and increasing the apoptosis, or programmed cell death, of cells damaged by carcinogens. These three mechanisms are believed to be involved in the protection against the development and growth of cancer cells. Led by Dr Richard Le Leu at Flinders University in South Australia, and published in The Journal of Nutrition, a new animal study demonstrated that the combination of natural high amylose corn resistant starch and the probiotic bacteria Bifidobacterium lactis increases apoptosis of cells damaged by carcinogens by more than 30 percent. The study also confirmed that high amylose corn RS2 positively influenced biomarkers for colonic health. It reduced large intestinal pH; increased the growth of lactobacilli and bifidobacteria; and increased short-chain fatty acids, including butyrate. Butyrate is the preferred energy source for healthy colon cells and is important for colon health.6

—Rhonda Witwer/National Starch Food Innovation

References
1. Brown I, et al. Fecal numbers of bifidobacteria are higher in pigs fed Bifidobacterium longum with a high amylose cornstarch than with a low amylose cornstarch. J Nutr 1997; 127:1822-7.
2. Scheppach W. Effects of short-chain fatty acids on gut morphology and function. Gut 1994; 35(1 Suppl):S35-8.
3. Andoh A, et al. Role of dietary fiber and short-chain fatty acids in the colon. Curr Pharmaceut Design 2003; 9(4):347-58.
4. Toden S, et al. Resistant starch prevents colonic DNA damage induced by high dietary cooked red meat or casein in rats. Cancer Biol Ther 2006; 5(1):e1-e6.
5. Birkett A, et al. Resistant starch lowers fecal concentrations of ammonia and phenols in humans. Am J Clin Nutr 1996; 63(5):766-72.
6. Le Leu RK, et al. A synbiotic combination of resistant starch and Bifidobacerium lactis facilitates apoptotic deletion of carcinogen-damaged cells in rat colon. J Nutr 2005; 135:996-1001.


All resistant starch is not the same

Resistant starches that appear in today's diets are broken down into four classifications:

RS1 — Physically inaccessible or digestible resistant starch, such as that found in seeds or legumes.

RS2 — Resistant starch that occurs in its natural granular form, such as uncooked potatoes, green banana flour and high amylose corn (ie, Hi-maize®).

RS3 — Resistant starch that is formed when starch-containing foods are cooked and cooled such as in bread, cornflakes, and cooked-and-chilled potatoes, or retrograded high amylose corn (ie, Novelose®).

RS4 — Selected chemically-modified resistant starches, not found in nature. Because resistant starches are defined by their physiological impact instead of their chemical structure, there are significant differences in how different types of resistant starches affect the body.

Different types of resistant starch must be labelled in different ways as food ingredients. Hi-maize RS2 analyses as dietary fibre and is listed as fibre on the nutritional information on product labels. The type-2 resistant starches such as Hi-maize are natural, so they can be designated simply as 'starch' or 'corn starch' on food product labels. Type-3 resistant starch such as Novelose labels as 'maltodextrin.'

For other classes of resistant starch, the labels vary. Chemically modified starches (such as RS4) must be labelled as 'modified food starch.'

—RW


Select Suppliers: Gut health ingredients focus on fibre and beneficial bacteria

BioGaia is an innovative company specialising in probiotics. The company developed and launched the first-ever probiotic drinking straw, LifeTop Straw. A recent 80-day study in Sweden showed that workers are less likely to take days off with colds and gastroenteritis when taking a daily dose of its Lactobacillus reuteri.
www.biogaia.com

CNI specialises in Fibregum, a gum acacia, which is traditionally consumed to prevent and treat gastrointestinal disorders. Fibregum is said to modulate intestinal flora by arriving intact in the colon where it is slowly and totally fermented by beneficial intestinal flora. Of note, Fibregum does not exhibit laxative side effects and is suitable for baked goods, cereal bars, biscuits and more, with a medium or low glycaemic index.
www.cniworld.com

Danisco Litesse is a prebiotic fibre clinically demonstrated to promote a healthy digestive system. It is well tolerated compared to other prebiotics. Known as a premium bulking ingredient, Litesse is a speciality carbohydrate that is 90 per cent prebiotic fibre. Used to make baked goods, nutrition bars, frozen desserts, beverages and confections sugar free, low glycaemic, low calorie.
www.danisco.com/sweeteners

GTC Nutrition, a business unit of Corn Products International, markets a range of branded ingredients, including NutraFlora, a short-chain fructo-oligosaccharides (scFOS) prebiotic fibre. Derived from cane or beet sugar, NutraFlora supports the growth of beneficial probiotic bacteria, which in turn provides health benefits such as improved calcium absorption and a strong immune system.
www.gtcnutrition.com

Institut Rosell is the Canadian leader in probiotics development. The company's aggressive investment in research has manifested in clinical trials in its patented probiotic strains in boosting the immune system, inhibiting pathogenic bacteria colonisation, correcting digestive tract imbalances, and maintaining vaginal and urinary tract health.
www.lallemand.com

Kalys is a French supplier of natural additives and thickeners for the food industry. In particular, soluble fibres consist mainly of hydrocolloids and gums, renowned for viscosity and gelling abilities. The company's gums can be combined with gelling agents to improve gel structure and cohesiveness without building too much viscosity.
www.kalys.com

National Starch Food Innovation markets Hi-maize 5-in-1 Fiber, a natural resistant starch with five health benefits: weight, glycaemic and energy management, digestive health, and high tolerance. Hi-maize holds less water than other insoluble fibres, which results in easier ingredient mixing and higher productivity.
www.foodinnovation.com

Nebraska Cultures developed the popular DDS-1 strain of Lactobacillus acidophilus and markets a line of probiotic ingredients for gut health. The company supplies custom-manufactured micro-organisms, either individually or in combination, and with or without enzymes, colostrum or phytonutrients.
www.nebraskacultures.com

Orafti Group produces prebiotic products Beneo brand inulin and oligofructose. Inulin can replace carbohydrates with fibre as far as on-pack declaration is concerned. Oligofructose behaves like sugar, although it is not as sweet. When consumed, the prebiotics are not digested, but reach the intestines intact where they ferment. The beneficial bifidobacteria are selectively stimulated, giving it its prebiotic effect. Beneo Synergy1 is a unique composition of oligofructose and inulin that has been specifically formulated to improve digestive health in general and bone health in particular.
www.orafti.com

Probi patents and documents probiotic bacteria. To date, the company has seven patents on probiotics' benefits on gastrointestinal disorders. Licensees include Danone, Sk?nemejerier, Institut Rosell and Health World.
www.probi.com

Proliant reports irritable bowel syndrome benefits with its ImmunoLin branded ingredient — an immunoglobulin protein isolate with immune-enhancing effects. The company, which specialises in bioactive proteins and peptides, has more than 50 studies showing ImmunoLin supports immune response in animals.
www.proliantinc.com


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