Prebiotics and immune responses.

Abstract

Feeding breast milk of healthy mothers is associated with a lower incidence of infectious and allergic diseases. Although this effect is of multifactorial origin, it is widely accepted that the entire intestinal flora of breastfed infants provides anti-infective properties and is an important stimulating factor for the postnatal development of the immune system. Clearly, the effect of human milk on the postnatal development of the intestinal flora cannot be attributed to a single ingredient. It is generally accepted, however, that human milk oligosaccharides play a key role in this matter (1). The composition of human milk oligosaccharides is very complex. As they are resistant against digestion, they can be detected in the faeces as well as in the urine of breast-fed infants (2). This low or absent digestibility is a prerequisite for prebiotic activities of dietary compounds (3). Apart from their prebiotic effects, there is also evidence that human milk oligosaccharides act as receptor analogues to inhibit the adhesion of pathogens on the epithelial surface (1) and interact directly with immune cells (Eiwegger Th, et al., unpublished data). Due to their complexity, oligosaccharides with structures indentical with human milk oligosaccharides are not available as dietary ingredients. Searching for alternatives, a mixture of neutral galacto-oligosaccharides (GOS) and fructo-oligosaccharides (FOS) have been identified as effective prebiotic ingredients during infancy (5). More recently, also acidic oligosaccharides such as pectin hydrolysate are under investigation (6). In several clinical trials it could be demonstrated that feeding a formula supplemented with a mixture of GOS and long-chain FOS results in an entire intestinal flora similar to that found in breast fed infants (7). Comparable to human milk oligosaccharides, GOS and FOS stay present during the whole gastrointestinal passage and are therefore detectable in the faeces of infants fed a GOS/FOS supplemented formula. With regard to stool characteristics, there was a significant influence of GOS/FOS in preterm as well as term infants: feeding the oligosaccharides-supplemented formula increased the stool frequency and softened the stool consistency in comparison to a standard formula so that stool characteristics could be achieved which were very similar to those of human milk fed infants (5). In a study in term infants the effect of different concentrations of the GOS/FOS mixture was tested in parallel by a traditional plating technique and a modern molecular biologic technique (7). Whereas with the plating technique, only living bacteria can be detected, all bacteria are counted with the molecular biologic technique. The results obtained by the two methods are shown in Figure 1. They clearly indicate that with the use of the GOS/FOS mixture, the number of bifidobacteria increases and the effect is much more pronounced for the living bacteria than for the total number of bacteria. Short-chain fatty acids (SCFA) are an important marker of the bacterial metabolism in the intestine. Invitro experiments focusing on the short SCFA synthesis by the faecal flora could demonstrate that the SCFA synthesis from GOS/FOS mixture was comparable to the synthesis from a quantitatively equivalent neutral human milk oligosaccharides fraction (7). Similar results were obtained in-vivo by measuring the fatty acid pattern in faeces from infants fed a formula supplemented with GOS/FOS: The faecal SCFA pattern was similar to that observed in breast fed infants (8). The results are in line with the observation that during a 28-day feeding period the faecal pH decreased in a group of term infants fed a GOS/FOS supplemented formula similar to breast fed infants, whereas the faecal pH in infants fed a nonsupplemented standard formula increased (5). Increased numbers of bifidobacteria and a decreased faecal pH are contributing to a reduction of clinically relevant pathogens, either expressed in absolute numbers or as percentage of total bacteria. In an animal study using the mouse vaccination model as recommended by international governmental guidelines (6), feeding GOS/FOS significantly stimulated the cellular (i.e., Th1/Th2) immune balance. In an animal model for allergic hypersensitivity using ovalbumin as allergen, dietary GOS/FOS inhibited the allergic inflammation (7). In summary, the data demonstrate that an infant formula supplemented with a mixture of GOS/FOS stimulates the entire intestinal flora and results in the production of physiologically important bacterial metabolites as well as a faecal pH similar to influences of human milk feeding. These effects are accompanied by stool characteristics close to those of breast-fed infants and by a Address correspondence and reprint requests to Prof. Gunther Boehm, Director Infant Nutrition Research Germany, Milupa GmbH & Co, KG Bahnstrasse 14-30, D-61381 Friedrichsdorf; Fax: 0049-6172991862 (e-mail: guenther.bohem@milupa.de). Journal of Pediatric Gastroenterology and Nutrition 39:S772–S773 © June 2004 Lippincott Williams & Wilkins, Philadelphia