OVERVIEW OF PREBIOTIC CONCEPT
15.4 OVERVIEW OF PREBIOTIC CONCEPT
In contrast to probiotics that have been the subject of research for a hundred years, 42 the development of prebiotics as a functional food is recent and rapidly expanding. The notion of prebiotics stemmed from the observation that resistant carbohydrates such as oligosaccharides are selectively fermented by bifidobacteria and can contribute to human health by inducing changes to the indigenous intes-
tinal microflora without the need for ingestion of live microorganisms. 43 The latest definition accepts as prebiotic any “non-viable food component which evades digestion in the upper gut, reaches the colon intact and is selectively fermented
by beneficial bacteria in the gastro-intestinal tract.” 44 Currently, most of the food components classified as prebiotics are low to medium molecular weight carbo- hydrates. High molecular weight carbohydrates such as dietary fibers are not
classified as prebiotics because they are not selectively fermented. 45 Recognized prebiotics are primarily built from glucose, galactose, xylose, and fructose (Table
15.3). Inulin, fructo-oligosaccharides (FOSs), and lactulose are prebiotics with the most documented effects in vivo due to their widespread commercial availability. Oligosaccharides containing other monosaccharides, such as arabinose, rhamnose, glucosamine, and galacturonic acid, are also under study (Table 15.4).
The mechanism underlying the selective fermentation process is still unclear. For example, the relationship between molecular weight and selectivity has not been clarified yet. An increase of selectivity is seen when polysaccharides decrease
in size, for instance, with xylan to xylo-oligosaccharides, 46 dextran to isomaltose, 47 and pectins to pectic oligosaccharides. 48 A better understanding of the relation between structure of oligosaccharides and functional benefits in the gut may lead to the manufacture of prebiotics with enhanced selectivity that could be targeted toward particular strains in the commensal flora.
TABLE 15.3 Commercially Available Existing Prebiotics
Oligosaccharides
Structure
Natural Occurrence
Manufacturing
Inulin
Hydrolysis of inulin by inulinase; synthesis from Fructo-oligosaccharides
Fru β2 → (1Fru) n , n = 20 Onion, chicory, banana, inulin
sucrose by β- fructosyl transferase Lactulose
Fru β2 → (1Fru) n , n = 2–5 from chicory
Chemical isomerization of lactose Lactosucrose
Gal β1 → 4Fru
None
Gal β1 → 4Glcα1 ↔ 2βFru
None
Synthesis from lactose and sucrose by β-fructo-
furanosidase
Trans-galacto-
Synthesis from lactose syrup by β-galactosidase oligosaccharides
Tri- to pentasaccharides with:Gal β1
Human and cow milk
→ 6GalGalβ1 → 3Gal linkages
Functional F Isomalto-oligosaccharides
Soybean oligosaccharides
Gal α1 → 6Glcα1 ↔ 2βFru
Soybean whey
Extraction from whey
Glc α1 → (6Glc) n , n = 1–4
Cornstarch
Synthesis from starch using α-amilase, pullulanase,
α-glucosidase
Gluco-oligosaccharides
Di- to heptasaccharides with:
Oat β-glucans
Sucrose + maltose/glucosyl transferase
Glc α1 → 2Glc
ood Carboh
Glc α1 → 6Glc linkage
ydrates
Probiotics, Prebiotics, and Synbiotics
TABLE 15.4 Newly Developed Oligosaccharides for Use as Prebiotics
Oligosaccharides
Structure
Natural Occurrence
Manufacturing
Gentio-oligosaccharides
Glu β1–6Gluβ1–6] n , n = 1–5
Chito-oligosaccharides
Glc β1–4Glc
Mucopolysaccharides
Xylo-oligosaccharides
Xyl β → 4Xyl
Corn cobs, oat spelt
Xyl β → 4Xyl
Corn cobs, oat spelt
Endodextranase Pectic-oligosaccharides
Glc α1 → (6Glc) n , n = 1–4
Dextran
Endoglucanase Endoarabinanase Arabino-galacto-oligosaccharides
Pectins Soybeans
Rhamnogalacturonase Arabino-oligosaccharide
Sugar beet
Endogalacturonase Rhamno-galacturo-oligosaccharides
Apple
Polygalacturonic acids
Galacturonic-oligosaccharides Sialic acid oligosaccharides
N-acetyl neuraminic acid
Human milk, κ-casein, lactoferrin
Functional Food Carbohydrates
15.4.1 E ASE OF U SE OF P REBIOTICS
Unlike probiotics, prebiotics are nonviable and reach the colon intact. These prop- erties confer to prebiotics considerable advantages. Their food manufacturing prop- erties, such as thickening agents or sweeteners, make them more amenable to industrial processes. Prebiotics have a longer shelf-life than probiotics and can be incorporated into a large variety of food, such as infant formulae, weaning food, cereals, and confectionery, as well as beverages, dairy products, and dietary supple- ments. Their versatility has major potential, but their use is still underrepresented in countries other than Japan.
15.4.2 S IDE E FFECTS
Possible side effects may be encountered when using prebiotics. Due to the resistance of prebiotics to digestion in the upper intestinal tract, the volume of material arising in the colon and the volume of fermentation end products are increased. An increase in stool frequency and stool weight is often reported in human feeding trials. 49–51 Absorption of a large dose (>20 g/day) of prebiotic such
as inulin or lactulose may lead to a laxative effect. 52 It is critical that newly developed products are selective toward non-gas producer bacteria, as gas disten- sion may discourage the intake of prebiotics.
15.4.3 D OSE E FFECT
Optimum doses of prebiotics have been determined for common prebiotics such as FOSs and trans-galacto-oligosaccharides in various populations. Doses of FOSs administered in feeding and clinical trials range from 3 to 20 g per day in adults and 0.4 to 3.0 g per day in infants. 52–54 These doses were found in agreement with the amount of naturally occurring oligosaccharides ingested in a diet rich
in vegetables. 55 A minimal intake of 4 to 10 g per day for induction of a bifidogenic effect is often suggested, but there is currently no recommended intake available. 44
15.4.4 P URITY AND S AFETY OF P REBIOTICS
Due to limitations in the manufacturing process, current prebiotic preparations are generally mixtures of polysaccharides of various chain lengths. The presence of mono- and disaccharides may hinder the specificity of the prebiotic. Chemical extraction of oligosaccharides from food may also result in undesirable color or flavor. To overcome these issues, new enzymatic technologies providing higher
oligosaccharide selectivity and more palatable properties are developed. 56 The risk of bacteremia associated with prebiotics is probably negligible. Bifidobacteria and lactobacilli are indigenous inhabitants of the gut microflora and also the major organisms targeted by prebiotic dietary management strategies; the proliferation of these populations has not lead to pathogenesis.
Probiotics, Prebiotics, and Synbiotics
15.4.5 GRAS S TATUS AND P ERSISTENCE OF E FFECT
Existing prebiotics are granted GRAS status. The natural occurrence of prebiotic compounds in commonly consumed food products and the long history of use have so far justified the absence of risk assessment for this type of functional food.
The persistence of prebiotic effects when their intake is stopped has not been well established. In many feeding studies, colonic microbial changes are observed after treatment with prebiotics, but the effect generally ceased with the interruption of treat- ment. 2,34 Long-term daily intake seems to be necessary to achieve optimum efficiency; however, few studies have looked at long-term consequences of prebiotic ingestion.