The pre- and probiotic puzzle

By pairing a specific prebiotic with a specific probiotic, a unique synbiotic compound is formed, creating an opportunity to provide targeted health benefits and a huge boost in immunity. Ian L Brown, PhD, explores

The important contribution to our health made by our intestinal microflora continues to be a growing focus of both international research and commercial activity. The consumption of probiotics has been linked to a broad range of physiological benefits through the changes affected on the indigenous microflora.1

Researchers have also focused on prebiotics — nondigestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon.2

Although initial studies in this area focused on fermentable substrates, such as inulin and fructo-oligosaccharides, a number of other dietary components, such as resistant starch, have been identified that can act as prebiotics.3

Considerable attention has been given recently to the concept of combining probiotics and prebiotics into what is called synbiotics, in order to produce health-enhancing functional food ingredients.2 The European Union-sponsored SYNCAN project is investigating the most suitable synbiotic preparation against carcinogenesis; it issued its first published findings in 2005.4

However, rather than combining just any probiotic and prebiotic, the concept of using a synbiotic offers the opportunity to provide a targeted benefit through matching the probiotic to a specific prebiotic. The type of prebiotic and probiotic strain or combination of strains used all can alter the potential to reinforce the immune system of the body and increase resistance to disease.

Indeed, only about 10 per cent of the probiotic lactic acid bacteria studied have proven strong immunosupportive effects.5 A synbiotic combination could improve the survival of the bacteria crossing the upper part of the gastrointestinal tract, thereby enhancing their effects in the large bowel.6

Increasing knowledge of the metabolism of prebiotics by probiotics is allowing researchers to consider specifically targeting such dietary intervention tools at specific population groups and specific disease states.7 Prebiotics can thus have a range of properties, including acting as a 'culture protagonist'8 to protect the viability of the probiotic in the food or during its transit through the upper GI tract,9 as a selective substrate for the probiotic,10 or as a substrate for a complementary beneficial microorganism.

Most of the studies published until now have involved two synbiotic preparations. The first is a single strain/single-fibre synbiotic comprising fermented oatmeal fibre with Lactobacillus plantarum strain 299.11 Since 2000, a number of studies have used the trademarked Synbiotic 2000.

This consists of a mixture of four probiotics from the lactobacillus genera: Pediacoccus pentosaceus 5-33:3, Leuconostoc mesenteroides 32-77:1, Lactobacillus paracasei subsp paracasei 19 and Lactobacillus plantarum 2362. The prebiotics to match in this formulation are beta-glucan, inulin, pectin and resistant starch. This synbiotic mixture has shown benefit in arteriosclerosis, Crohn's disease and chronic liver disease.12,13

The benefit of these probiotics is in their ability to survive in the low pH of the stomach and in the high-bile-acid content of the small intestine. Also, they can attach to colonic mucosa and temporarily colonise the large intestine. They can ferment various types of plant fibres, including inulin.5

Resistant starches
The recognition that a fraction of the starch consumed in our diets is resistant to digestion in the upper GI tract has led to scientific and nutritional interest in the physiological effects of resistant starch (RS).14

Due to the vast differences in form, structure and chemistry provided by RS, there is a corresponding range of opportunities available to tailor the type and form of RS for specific physiological effects,15 to provide appropriate functionalities for the preparation of foods,16,17 or act as a targeted prebiotic.

RS is present, usually in small amounts, in many of the starch-containing foods that people consume.18 However, it has been suggested that in Western diets, in order to maintain good colonic health, the amount of RS needs to be increased by two to three times.19

Initially, clinical studies mainly focused on sources of RS obtained from raw potatoes and green bananas. However, the first commercial source of RS in foods was obtained from high amylose maize.

This maize has a high gelatinisation temperature, which means that the granule can maintain its resistance to digestive amylases during many of the conditions that are used in the preparation of foods.

The impact of RS in the colon is generally associated with the beneficial stimulation of the colonic microflora and its action as a prebiotic.20 (Table 1)

It was observed that the inclusion of RS in the diet increased the production of short-chain fatty acids, with a special emphasis on physiologically important butyrate. The consumption of RS produces positive effects on a range of biomarkers of colonic health, including decreases in transit time, pH and various toxic metabolites, such as secondary bile acids, ammonia and phenols.

The beneficial stimulation of the colonic microflora can also lead to advantageous consequences such as increasing the bioavailability of micronutrients such as calcium,21 decreasing the symptoms of bacterially induced diarrhoea,22 improving insulin sensitivity,23 being involved in biotransformations such as the conversion of phytoestrogenic materials into more bioactive forms,24 increasing the immune response25 and potentially increasing lipid metabolism in the body.26,27

Synbiotics must match
The concept of synbiotics provides a means of promoting physiological improvements and providing the fermentative substrate to achieve this effect. The synbiotic can achieve benefits through outcomes such as the manipulation of the colonic microflora, the production of beneficial metabolites such as short-chain fatty acids, and the reduction in the numbers and activity of pathogenic bacteria.

Synbiotics offer the opportunity to provide a targeted benefit through matching the probiotic to a specific prebiotic

However, for the best effect, the probiotic and prebiotic needs to be carefully matched and not be just a random combination. These targeted synbiotics may offer a new means to protect against the development of or to treat a wide variety of lower GI complaints and diseases.

In addition, it is now recognised that the functioning of the GI tract can influence physiological activity elsewhere in the body, such as lipid metabolism, immune status and insulin sensitivity. Targeted synbiotics offer a potential means of preventing or treating many socially important health concerns, including obesity.

Although it is technically challenging to effectively maintain the viability of probiotics in processed foods, it is relatively easy to include prebiotics and in combination the prebiotic may assist in maintaining the viability of the probiotic micro-organism(s).

Ian L Brown, PhD, is a professorial fellow in the Department of Health and Behavioural Sciences, Wollongong University, Australia. Respond: [email protected] All correspondence will be forwarded to the author.

1. Tannock, GW. Probiotics: a critical review. Ed: GW Tannock. Horizon Scientific Press. 1999;1.
2. Gibson GR, Roberfroid MB. J Nutr 1995; 125:1401-12.
3. Brown I, et al. Food Australia 1998;50(12):603-10.
4. Van Loo J, et al. The SYNCAN project: goals, set-up, first results and settings of the hyuman intervention study. Br J Nutr 2005 Apr; (93 Suppl) 1:S91-8.
5. Bengmark S, Martindale R. Prebiotics and synbiotics in clinical medicine. Nutr Clinn Prac 2005 Apr; 20(2):244-61.
6. Roberfroid MB. Prebiotics and probiotics: are they functional foods? Am J Clin Nutr 2000 Jun; 71(6 Suppl):1682S-7S.
7. Rastall RA, et al. Modulation of the microbial ecology of the human colon by probiotics, prebiotics and synbiotics to enhance human health: an overview of enabling science and potential applications. FEMS Microbiol Ecol 2005 Apr 1; 52(2):145-52.
8. Conway PL. Scand J Nutr 2001; 45:13-21.
9. Wang X, et al. J Appl Microbiol 1999; 87:631-9.
10. Wang X, et al. J Appl Environ Microbiol 1999; 65(11):4848-54.
11. Johansson ML, et al. Administration of different lactobacillus strains in fermented oatmeal soup: in vivo colonization of human intestinal mucosa and effect on the indigenous flora. Appl Environmen Microbiol 1993; 59:15-20.
12. Kruszewska K, et al. Selection of lactic acid bacteria as probiotic strains by in vitro tests. Microecol Ther 2002; 29:37-51.
13. Ljungh A, et al. Isolation, selection and characteristics of Lactobacillus paracasei ssp paracasei isolate F19. Microbial Ecol Health Disease 2002; Suppl3:4-6.
14. Englyst et al. Eur J Clin Nutr 1992;46(suppl 2):S33-S50.
15. Nugent AP. Nutr Bull Brit Nutr Found 2005; 30(1): 27-54.
16. Brown IL. J AOAC Internat 2004; 87(3): 727-32.
17. Crawford C. FMBRA Bull 1987; 2:59-64.
18. Yue P, Waring S. Cereal Foods World 1998; 43(9):690-5.
19. Baghurst PA, et al. Food Australia 1996; 48(3):S1-S35.
20. Brown IL, et al. Scand J Nutr 2000; 44(2): 53-8.
21. Lopez HW, et al. J Nutr 2001; 131:1283-9.
22. Ramakrishna BS, et al. New Engl J Med 2000; 342:308-13.
23. Robertson MD, et al. Am J Clin Nutr 2005; 82:559-67.
24. Larkin T, et al. EUROFOODCHEM XI Biologically-active Phytochemicals in Foods: Analysis, metabolism, bioavailability and Function (UK). 2001.
25. Morita T, et al. J Gastroenterol Hepatol 2004; 19:303-13.
26. Higgins JA. J AOAC Internat 2004; 87(3):761-8.
27. Higgins JA, et al. Nutr Metab 2004; 1:8.

Targeted synbiotics: resistant starch and bifidobacteria
While much work has focused on oligosaccharides as prebiotics, the physiological effects of high-amylose maize starch (HAMS) granules have kindled interest in the prebiotic potential of these granules.

It has been shown that, in the gut, bacterial cells attached to a surface are more resistant to a hostile environment such as low pH and the presence of bile acids.1 The high concentration of resistant starch in the HAMS diet increases faecal bulk. The bulking capacity of resistant starch may markedly modify the pH of the stomach and dilute the bile acid level in the small intestine, enhancing the survival of probiotics.2

In a recent experiment, two synbiotic preparations were tested for their ability to increase the amount of apoptosis caused in the colonic tissue of rats after they had been exposed to the carcinogen azoxymethane.3 It had already been shown that HAMS could increase the amount of apoptosis in this model in a dose-responsive manner.4 Two probiotics were included in the experiment, a Lactobacillus acidophilus and a Bifidobacterium lactis, but only the bifidobacteria could utilise the HAMS directly.

In this study, neither of the probiotics in the absence of the prebiotic increased the apoptotic response compared to the control diet. However, the effect of the bifidobacteria on the apoptotic response significantly increased, by approximately 50 per cent, when consumed in the presence of HAMS. The lactobacillus did not increase the apoptotic response alone or in the presence of the HAMS.

The mechanism by which the apoptotic response is increased appears to involve more than the production and presence of butyrate in the colonic lumen. Bifidobacteria is not reported to produce butyrate in the colon, but these bacteria do attack the HAMS directly and this may provide nutrients, either from the RS directly or through the products of bacterial fermentation for other bacterial species that do produce butyrate. This results in an enhanced growth and/or activity of other bacterial species that may play a role in stimulating the apoptotic activity.

Studies are now under way to explore the long-term effects of this synbiotic combination in both animals and humans.

1. Brown I, et al. Food Australia 1998;50(12):603-10.
2. Wang X, et al. J Appl Environ Microbiol 1999; 65(11):4848-54.
3. Le Leu RK, et al. J Nutr 2005; 135: 996-1001.
4. Le Leu RK, et al. Carcinogenesis 2003; 24(8):1347-52.

Some beneficial interactions between resistant starch and probiotics/colonic microflora:
Prebiotic properties

  • Selectively utilized by bifidobacteria
  • Promotes growth of indigenous microbes: lactobacilli, bifidobacterium
  • Promotes probiotic growth and activity in vivo
  • Synbiotic promotion of beneficial physiological effects
  • Synergy with oligosaccharides; elevation of indigenous bifidobacteria

Production properties

  • Improves yield of probiotic cultures during growth
  • Improves survival of probiotic cultures during processing in food formulations
  • Synergy with other hydrocolloids for enhanced probiotic survival

Demonstrable health benefits

  • Reduces intestinal pathogen levels
  • Reduces symptoms of diarrhoea
  • Elevates colonic butyrate levels
  • Increases absorption of micronutrients
  • Improves colonic health
  • Increases lipid metabolism
  • Improves insulin sensitivity
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