A search through Mintel’s GNPD shows products combining probiotic cultures with dietary fiber have been primarily in the pet food and healthcare categories. While Stonyfield Farms has been a leader in this area, other manufacturers, such as Genesis Today’s recently launched Kiwi Cleanse Yogurt Smoothie with fiber and a blend of four probiotic cultures, will surely follow. -- PF Editors
Photo courtesy Mintel’s GNPD

Article: Synbiotics in Focus -- July 2010
Sofia Kolida, Bob Rastall and Glenn Gibson, The University of Reading

Chronic and acute gut disorders are a major and growing societal and financial concern. The pharmaceutical approach has been enormously valuable for treating disease. However, there has been an increasing emphasis on dietary-based approaches that reduce risk and act in a prophylactic manner. This is the basis of the “functional foods” concept, whereby dietary ingredients are used for purposes over and above their normal nutritional value1. The “Global Market Review of Functional Foods” estimates the worldwide functional food market will reach a value of at least $90.5 billion by 2013. The emergence of health-conscious consumers with a proactive approach of “prevention over cure” and the development of nutritional science have driven the growth of functional foods. Currently, around 60% of functional foods in use are targeted toward gastrointestinal health.

Probiotics and Prebiotics
The biological and clinical importance of the gut microflora in humans is becoming increasingly recognized by consumers and healthcare workers. Although it is known many disease states involve bacterial metabolism, the human gut microbiota may also be considered as extremely relevant for an improvement in host health2. For instance, Bifidobacteria and Lactobacilli can improve resistance to gut infections by directly inhibiting the growth of harmful bacteria, improving the immune response and producing vitamins. More speculatively, they have been implicated in reducing cholesterol levels, decreasing genotoxic markers and alleviating inflammatory conditions3. Scientific concepts underpinning directed modulation of the human gut microflora towards a more beneficial composition have had probiotics as a principal focus.

While probiotics have been ingested by humans for several hundred years, their development has progressed markedly over the last decade. Probiotics are live microbial food supplements that have a beneficial effect on the intestinal flora of the host, thereby leading to health improvements4. Probiotics must be safe (i.e., Generally Regarded As Safe, GRAS); they must be amenable to industrial processes necessary for commercial production; they must remain viable in the food product and during storage; they must persist in the gastrointestinal tract long enough to elicit an effect; and they must improve host health.

The use of live bacteria in the diet has been successful scientifically and economically over the last two decades.

However, there is debate over:
* Maintaining product integrity and consistency.
* Survivability in the product and following ingestion.
* The fact that probiotics are only amenable to use in a limited number of food sectors (as heat kills the strains).

Prebiotics are a far more recent concept than probiotics, being first developed in the mid-1990s5. They are dietary ingredients which can selectively enhance beneficial components of the indigenous gut microbiota, such as Lactobacilli or Bifidobacteria, and are finding increased application in the food sector.

Prebiotics were originally developed to selectively enhance beneficial components of the gut microbiota, such as Lactobacilli or Bifidobacteria. Prebiotics were originally defined as “non-digestible food ingredients that are selectively metabolized by colonic bacteria that have the capacity to improve health” 5. As such, their use is directed towards favoring beneficial changes within the indigenous gut microbial milieu. They are distinct from most dietary fibers, like pectin, celluloses and xylan, which are not selectively metabolized in the gut. Criteria for classification as a prebiotic are:
* Resists gastric acidity, hydrolysis by mammalian enzymes and gastrointestinal absorption.
* Fermentation by intestinal microflora.
* Selectively stimulates the growth and/or activity of intestinal bacteria associated with health and well-being.

Any dietary component that reaches the colon intact is a potential prebiotic; however, it is the latter of the three above criteria which is the most difficult to fulfill. Much of the interest in the development of prebiotics is aimed at non-digestible oligosaccharides, such as fructo-oligosaccharides (FOS), trans-galacto-oligosaccharides (TOS), isomalto-oligosaccharides (IMO), xylo-oligosaccharides (XOS), soy-oligosaccharides (SOS), gluco-oligosaccharides (GOS) and lactosucrose. In Europe, FOS, TOS and lactulose have been shown to be prebiotics, through numerous volunteer trials, as evidenced by their ability to change the gut flora composition after a short feeding period2. Some prebiotics, like inulin, occur naturally in several foods, such as leek, asparagus, chicory, Jerusalem artichoke, garlic, artichoke, onion, wheat, banana and oats, as well as soybean. However, these foods contain only trace levels of prebiotics, so developments have taken the approach of removing the active ingredients from such sources and adding them to more frequently consumed products, in order to attain levels whereby a prebiotic effect may occur (e.g., cereals, confectionery, biscuits, infant foods, yogurts, table spreads, bread, sauces, drinks, etc.) 6. TOS are manufactured from lactose and also are effective prebiotics.

A further concept for altering the gut microbiota for improved health exists. This is known as synbiotics and exploits both the above approaches. Simply put, a synbiotic is a mixture of a reliable probiotic with an efficacious prebiotic. The word “symbiotic” is derived from two Greek words which together translate as “together” and “life.” Use of the two words together signifies “synergy” in Greek. Synbiotics were originally defined as “a mixture of probiotics and prebiotics that beneficially affects the host, by improving the survival and implantation of live microbial dietary supplements in the gastrointestinal tract, by selectively stimulating the growth and/or activating the metabolism of one or a limited number of health-promoting bacteria, and thus improving welfare” 5. To these authors’ knowledge, this definition has not been altered markedly since. In contrast, both probiotics and prebiotics have undergone several definition changes in the last decade. (The latest versions are given in the chart “A Synbiotic Approach to Health.”)

Synbiotics were developed to overcome possible survival difficulties with probiotics. Hence, the approach would be to fortify strain activity (the probiotic) by incorporating a selective substrate for growth (the prebiotic) within the competitive gut ecosystem. A synbiotic is, therefore, a combination of a probiotic and prebiotic in the same product. The advantages are that a commercial probiotic with known benefits can be used, and the prebiotic aids the establishment of the organism in the complex gut environment. There is clearly great flexibility in the choice of probiotic micro-organisms and prebiotic (probably oligosaccharide), and how the best combination for a specific desired outcome can be determined. A good synbiotic would, therefore, exploit the positive properties of both the probiotic and the prebiotic ingredient.

The original synbiotic premise was that the selective substrate would be metabolized by the live addition in the gut. This would enhance probiotic survival, as well as offer the advantages of both gut microflora management techniques. A clear synbiotic would be a mixture of a Bifidobacterium with fructo-oligosaccharides or galacto-oligosaccharides. By combining the probiotic and prebiotic strategies previously described, additive or synergistic effects may be observed. Increased survival of probiotic bacteria would occur through simultaneous feeding, with a prebiotic being competitively utilized by the probiotic. In addition, the prebiotic may not only stimulate the growth or activity of the fed probiotic strain, but also indigenous beneficial bacteria in the gut. Taking this further, it may be feasible to identify separate categories of synbiotics.

Based on current concepts, two types of synbiotic approaches may exist. The first is “complementary,” whereby the probiotic is chosen based on specific, desired beneficial effects on the host, and the prebiotic is separately chosen to selectively increase specific populations of indigenous beneficial microbiota components. The second is “synergistic,” whereby the probiotic is again chosen based on specific beneficial effects on the host; the prebiotic also specifically stimulates the growth and activity of the chosen probiotic.

 In this case, the prebiotic is selected to have a higher affinity for the probiotic and is chosen to improve its survival and implantation in the host. It may also boost the levels of the beneficial host gastrointestinal microbiota, but the primary target is the ingested probiotic. (See the two illustrations “Complementary Synbiotics” and “Synergistic Synbiotics.”)

As well as Bifidobacteria, Lactobacilli have been extremely popular probiotics. However, most confirmed prebiotics selectively stimulate the former, not the latter, in hitherto conducted human studies2. As such, it is difficult to identify synergistic synbiotics for Lactobacilli. However, a probiotic Lactobacillus spp., in concert with fructans or galactans, would constitute a complementary synbiotic.

The expected benefits of the combination of prebiotics with probiotics could be:
* Improved survival during passage of the probiotic(s) through the upper gastro-intestinal tract.
* A more persistent effect of the probiotic(s) within the host gut ecosystem.
* The prebiotic component may stimulate not only the growth of the probiotic strain(s), but also indigenous components of the colonic microbiota that are considered to be beneficial.
* Health advantages from the live microbes that may not ensue from prebiotics alone.

Most synbiotics launched to date have been in the dairy industry: from a technical perspective, it is largely survivability of the probiotic strains that dictates what synbiotics can be developed, as prebiotics can be used in many food applications. Powdered dietary supplements are another application area.

Technical challenges are not the only barrier to development of the synbiotic market; consumer understanding presents an equally large obstacle. Manufacturers have already included both probiotics and prebiotics in formulations, but may not market the product as a synbiotic.

As the population continues to age, there is increasing susceptibility among consumers to morbidity and mortality. The functional food industry perception of the importance of gut microbiology in human health and nutrition has led to a major increase in prebiotic- and probiotic-based products. Synbiotics are combinations of both, which may induce the positive attributes of both pro- and prebiotics. NS
Sofia Kolida, Bob Rastall and Glenn Gibson are in the Department of Food and Nutritional Sciences, The University of Reading, Whiteknights, Reading, UK. Author contact information: Tel: +44.118.3788715, g.r.gibson@reading.ac.uk. Please also see www.reading.ac.uk. For research at the university’s Department of Food and Nutritional Sciences, see http://tinyurl.com/2bps6k4. For more reading on the subject, the book, Prebiotics: Development and Application, edited by G.R. Gibson and R.A. Rastall, is now available.

1 GR Gibson and CM Williams (eds.) 2000. Functional Foods: Concept to Product. Woodhead Publishing Limited, Cambridge.
2 GR Gibson and MB Roberfroid (eds.) 2008. A Handbook of Prebiotics. Taylor & Francis, Boca Raton.
3 Steer T, et al. 2000. Nutr Res Rev. 13:229-254.
4 Fuller R. 1989. J Appl Bacteriol. 66:365-378.
5 Gibson GR, Roberfroid MB. 1995. J Nutr. 125:1401-1412.
6 Gibson GR, et al. 2004. Nutr Res Rev.17:259-75.