Prebiotics

Stephanie Allen

Liz Wells

Advanced Research Dietitians HoNEI, Hull york Medical School, University of Hull

Stephanie Allen is an Advanced research dietitian working for the hull york medical School at the University of hull. She originates from Australia where she trained and worked as an Accredited Practising dietitian.

liz Wells is an Advanced research dietitian working at the hull york medical School. Prior to entering the world of academia she worked as a critical care specialist and a macmillan oncology dietitian.

in the past, research and interest has been predominantly focused on probiotics but in the context of human health the future looks bright for prebiotics, with a wealth of information being gathered in the last two decades (1). they are considered attractive to researchers and industries, not only due to their nutritional benefits, but also their economic benefits and are used in food, particularly in the production of functional foods (2).

Prebiotics are defined as ingredients that selectively stimulate the growth and/or activity of one or a limited number of species/genera of bacteria in the microbiota, thereby providing benefits to the health and well-being of the host (2). According to Gibson et al (3), a food component must meet the following requirements to be considered prebiotic: • be resistant to salivary, pancreatic and intestinal enzymes; • be fermentable by the intestinal microbiota; • selectively stimulate the growth and/ or activity of intestinal bacteria to contribute to health and well-being.

Currently, only non-digested carbohydrate molecules, a range of di-, oligo- and polysaccharides, resistant starches and sugar polyols have been claimed to have prebiotic properties (4). Once prebiotics have reached the colon, they are hydrolysed to small oligomers and monomers which are then further metabolised by anaerobic bacteria (5). This process, known as fermentation, serves the bacteria, as it provides energy for proliferation and results in the production of short chain fatty acids (e.g. acetate, propionate, butyrate and L-lactate). The process also yields production of gases (H2, CO2, CH4) which are metabolically useless to the host, but now assist us in determining the degree to which these prebiotics are broken down, using the method of breath testing (6).

bENEfITS of PREbIoTICS The list of prebiotic effects on the human body is growing as more is discovered about their mechanism and a deeper understanding is gained. It is postulated that prebiotics can influence the immune system, aid blood lipid control, aid mineral absorption and prevent the development of colon cancer.

LIPID PRofILES Prebiotics may have a role in the prevention of chronic diseases as they play a role in lipid level controls. Deranged lipid profiles, along with smoking and hypertension, is one of the key risk factors for cardiovascular disease. It is estimated that half of British adults have raised serum cholesterol levels, which rises with age. One of the by-products of fermentation of prebiotics is acetate, a gluconeogenic substrate, which might contribute to inhibition of cholesterol synthesis and regulation of adipose. It has been demonstrated mainly by a reduction in triglyceridaemia and only a relatively slight decrease in cholesterolaemia mostly in (slightly) hypertriglyceridaemic conditions (7).

GASTRoINTESTINAL Prebiotics are also thought to have a positive effect on bowel health as they specifically stimulate the growth of Bifidobacteria and Lactobacilli in the microbiota. Lactobacilli aids lactose digestion, resistance to infections such as Salmonellae, prevents travellers’ diarrhoea, helps relieve symptoms of irritable bowel syn-

drome and decreases constipation (8). Bifidobacteria stimulates the immune system, produces B vitamins, inhibits pathogen growth, decreases blood ammonia, decreases blood cholesterol and helps promote gut flora returning to normal after antibiotic use (9). However, it must be noted that evidence exists to suggest that excessive consumption of non-digestible oligosaccharides may cause intestinal discomfort, flatulence or even diarrhoea. It is suggested that galacto-oligosaccharide consumption higher than 20g/day and fructo-oligosaccharide consumption higher than 40g/day are reported to cause diarrhoea (6).

MINERAL AbSoRPTIoN The primary site for calcium absorption is via the small intestine, but it is thought that secondary absorption occurs throughout the length of the gut. It is hypothesised that prebiotics enhance calcium absorption by decreasing the pH of the gut lumen and by increasing the bioavailability of calcium by extending the site of mineral absorption towards the large intestines. The most active product for enhancing calcium and magnesium absorption is oligofructose-enriched inulin. Prebiotics have also been found to improve the absorption of iron, zinc and magnesium (10).

CoLoN CANCER Colon Cancer is the second most common cancer after lung cancer in the United Kingdom. The aetiology is not fully understood but genetics, smoking, diet and inactivity have all been implicated. Specific dietary factors such as low fruit and vegetable intake, high red meat and a high processed food intake have been implicated.

When substrates such as non-digestible oligosaccharides, fibre, undigested proteins or endogenous secretions enter into the large colon, their transit time slows allowing time for the microbiota to begin acting on them. It is speculated that prebiotics may protect against colon cancer via two methods. Short chain fatty acids, such as butyrate, are produced in the colon when prebiotics are fermented. Butyrate decreases the risk of colon cancer through stimulating apoptosis in colon cell cancer lines. Known butyrate producers in the colon are clostridia and eubacteria. Butyrate is largely metabolised by the colonic epithelium serving as a major energy substrate for healthy colonocytes as well as a regulator of cell growth and differentiation (1).

The second mode of action of prebiotics in colon cancer prevention is the subversion of colonic metabolism from protein and lipid metabolism. Protein degradation in the colon increases toxic substances such as ammonia and amines, which is linked to colon cancer and Inflammatory Bowel Disease. Prebiotics shift bacterial metabolism in the colon towards more benign end products (7).

WHy ARE PREbIoTICS PoPULAR WITH THE fooD INDUSTRy? The caloric value of non-digestible oligosaccharides, such as galacto-oligosaccharides, fructo-oligosaccharides and lactulose has been estimated to be 1.02.0kcal/g, which is approximately 30 to 50 percent of digestible carbohydrates such as sucrose (please note that lactulose is a disaccharide that possess similar properties to the oligosaccharides). Specifically, galacto-oligosaccharides have a caloric value of 1.73kcal/g (11). Due to their small caloric value, they are often added to low-calorie diet foods and can be used to mask the aftertastes produced by some of these intense sweeteners (12).

Fermentable sugars, such as sucrose, are significant contributors to dental decay, as their digestion is started by the salivary enzymes. This results in residual food in the oral cavity which can provide an energy source for cariogenic bacteria (13). Unlike starch and simple sugars, non-digestible oligosaccharides are not utilised by the mouth microflora and, therefore, do not produce acids or polyglucans (cariogenic compounds). This enables them to be used as low cariogenic sugar substitutes in food products and, as a result, are often added to confectionary, chewing gums, yoghurts and drinks (12).

HUMAN MILK oLIGoSACCHARIDES During the first months of life, infants rely on milk as their sole source of nutrition, whether this is from infant formula or human milk. Breastfeeding has been shown to improve the development of the immune system of the newborn, resulting in protection against enteric and respiratory infections (14). The beneficial effects of human milk cannot be solely attributed to a single ingredient, but it is generally accepted that human milk oligosaccharides (HMO) play a key role (14).

HMOs are the third largest component of human breast milk and are produced in the mammary gland where several monosaccharides are added to

a lactose core by action of specific transferases (15). It is generally accepted that HMO are comprised of five monosaccharides: D-glucose, D-Galactose, Nacetyl-glucosamine, L-fucose and sialic acid (16).

The intestinal microbiota of breastfed infants is generally dominated by Bifidobacteria and lactic acid bacteria, whereas the intestinal microbiota of formula-fed infants is more similar to that of adults, in that it contains heavier loads of bacteroides, clostridia and enterobacteriaceae (17). It is thought that this intestinal microbiota is partially due to the special composition of HMOs which makes it inaccessible to intestinal enzymes and, therefore, renders it indigestible, and satisfying the criteria for prebiotics (18).

Table 1: Probiotics vs prebiotics (21)

Probiotics

Probiotics are living non-pathogenic micro-organisms which, when ingested, exert a positive influence on host health or physiology

Probiotics are susceptible to environmental stresses such as heat damage during manufacturing processes or gastric acid and bile salts in the GI tract

Probiotics cannot thrive without prebiotics

The major source of probiotics for humans is dairy-based foods containing intestinal species of Lactobacillus or bifidobacterium Due to their complexity, oligosaccharides with structures identical to human milk, are not available as dietary ingredients (14). In a recent review it was noted that even though great progress has been made in synthesizing kilograms of HMO, the technology has not yet reached its full potential to consistently and efficiently produce large amounts of HMO that could, therefore, be added to infant formulas [19]. Instead of HMOs, galactooligosaccharide (GOS) and/or fructo-oligosaccharides (FOS) are often added to infant formulas with the expectation that they will produce the prebiotic effect which will help promote bacterial microflora (16, 20).

Prebiotics

Prebiotics are non-digestible food ingredients that benefit the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon, that have the potential to improve host health

Prebiotics are not affected by environmental stresses and do not get damaged whilst in transit to the colon

Prebiotics provide the fuel for the probiotic bacteria to flourish on

Prebiotics are readily available in fruits, vegetables, wheat products and pulses

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