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.