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How Prebiotic Oligosaccharides could effect the infant immune system-clinical data |
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About the Author: This article was written by Guido E. Moro, Milan, Italy
The information in this article is correct at date of publication: 2007
Opinions expressed by the author are not necessarily those of the publisher or editorial staff.
Prebiotics: Clinical Data on Immune-modulating Effects
The latest research on the carbohydrate composition of human milk has confirmed that oligosaccharides represent one of its main components. Oligosaccharides reach a concentration of 20 g/l in colostrum and after a decreasing phase in the first month they become stable at a level of about 12 g/l in mature human milk. There is growing evidence that the oligosaccharides of human milk play an important role in the prebiotic effect (essentially bifidogenic) as well as the anti-infective properties of human milk. In order to obtain the benefits of an intestinal flora with a high proportion of bifidobacteria in formula-fed infants, a new prebiotic mixture was developed based on the results of research into human milk oligosaccharides.
The mixture contains 90% of low molecular weight galacto-oligosaccharides (GOS) and 10% of high molecular weight fructo-oligosaccharides (FOS). FOS, like inulin, are found in plants such as wheat, onion, garlic, artichokes and chicory. GOS are usually produced during enzymatic hydrolysis of lactose by the enzyme β-galactosidase.
Influence on intestinal flora
The dose dependant prebiotic effect of this GOS/FOS mixture has been consistently demonstrated in preterm as well as in term infants
1,2. The increased number of Bifidobacteria was accompanied by a reduction of clinically relevant pathogens
3,4. Additionally, the Bifidobacteria sub-species, as measured by real time polymerised chain reaction (PCR), demonstrated that the sub-species of Bifidobacteria were also stimulated in a way similar to that in breastfed infants
5. These findings are underlined by the observation that the bacterial metabolic products, as measured by stool pH and faecal short chain fatty acid pattern, were similar to those found in breast-fed infants. Apart from the specific inhibitory effects of pH and SCFA on pathogens, these metabolites also clearly indicate that the GOS/FOS prebiotic mixture at a concentration of 0.8 g/100 ml influences the entire flora to develop in a way similar to that found in breastfed infants.
Figure 1. Study to investigate the effect of a prebiotic mixture of galacto- and long chain fructo-oligosaccharides on the incidence of atopic dermatitis: Trial profile
Influence on immune modulation
In a mouse model for respiratory allergy induced by ovalbumin, the GOS/FOS mixture has been shown to impair several biomarkers for allergy. The observed effects included a dose dependent reduction in serum IgE levels and reduced hyperactivity of the bronchial system after stimulation. According to the recommendations of ILSI and WHO these data would be particularly relevant if they could be combined with findings in humans. In order to obtain the required data on human subjects, a study on 259 term infants with family history of allergy was performed: 206 infants completed the study (102 in the GOS/FOS group and 104 in the placebo group).
Breastfeeding was recommended to all parents. If the mother decided to start bottle feeding the infants were randomly assigned to one of the two formula groups (Figure 1; one group received a formula with 0.8 g GOS/FOS mixture per 100 ml and one group received the same formula supplemented with 0.8 maltodextrin/100 ml as placebo).
The protein fraction of both formulas comprised extensively hydrolysed protein. The infants were investigated for clinical evidence of atopic dermatitis at 3 and 6 months of age. Up until the end of the 6 months study period, 10 infants in the GOS/FOS group (9.8%) and 24 (23.1%) in the placebo group developed atopic dermatitis
6. The difference in the incidence was statistically significant (p<0.05) (Figure 2).
Figure 2. Reduced incidence of atopic dermatitis in 6 months old infants after feeding a HA formula with GOS/FOS (n=102) or placebo (n=104) (Moro
et al. 2006)
In a subgroup of 84 term infants blood samples were obtained at the age of 6 months for the analysis of antibodies. Among these infants, 41 received the formula supplemented with GOS/FOS mixture and 43 the placebo formula. Total IgE, total IgG4 and specific antibodies to vaccination (HEXAVAC) were measured by ELISA techniques at 6 months of age. There was a significant reduction of total plasma IgE levels in the infants fed the GOS/FOS mixture when compared to infants fed the placebo. This reduction was even more striking in infants who became atopic, reaching a difference of approximately 50%. This was accompanied by an increase of plasma IgG4 levels resulting in a significant decrease of the IgE/IgG4 ratio. An increase in IgG4 and a decrease in IgE are important predictors for success in the treatment of allergy using immunotherapy
7. Thus, the IgE/IgG4 ratio is widely used as a predictive biomarker for the development of allergy. The specific antibodies against the vaccination produced during the first months of life were not influenced, indicating that the reduction of the total IgE levels is not simply an effect of a general reduction of antibody titres.
Conclusions In summary, the present data demonstrate a significant effect of this prebiotic mixture of GOS/FOS on the immune system, resulting in a reduced incidence of atopic dermatitis, decreased IgE levels and increased IgG4 levels at 6 months of age in children at risk for allergy. Although the mechanisms of the effects of dietary oligosaccharides (either from human milk or alternative sources) are not fully understood, the development of a balanced intestinal flora is a key element of this relationship. Thus, achieving an intestinal flora with the GOS/FOS mixture which is closer to the flora of breast-fed infants is highly indicative of an improved immune system. Dietary oligosaccharides can positively influence the post natal development of the immune system, suggesting a potentially important role in the Th1/Th2 balance and in allergy prevention.
References
- Moro G, Minoli I, Mosca M, et al. Dosage related bifidogenic effects of galacto- and fructo-oligosaccharides in formula fed term infants. J Pediatr Gastroenterol Nutr 2002; 34:291-5.
- Boehm G, Jelinek J, Stahl B, et al. Prebiotics in infant formulas. J Clin Gastroenterol 2004; 38:S76-9.
- Boehm G, Lidestri M, Casetta P, et al. Effect of increasing number of intestinal Bifidobacteria on the presence of clinically relevant pathogens. J Pediatr Gastroenterol Nutr 2003; 36:578.
- Knol J, Steenbakkers J, van der Linde E, et al. Bifidobacterial species that are present in breast fed infants are stimulated in formula fed infants by changing to a formula containing prebiotics. J Pediatr Gastroenterol Nutr 2002; 34:477.
- Knol J, Haarman M, Kafka C, et al. Quantitative real time PCR of bifidobacterial species of infants receiving a prebiotic infant formula. J Pediatr Gastroenterol Nutr 2004; 39: S67-8.
- Moro G, Arslanoglu S, Stahl B, et al. A mixture of prebiotic oligosaccharides reduces the incidence of atopic dermatitis during the first six months of age. Arch Dis Child 2006; 91:814-9.
- Akdis CA, Blesken T, Akdis M, et al. Role of interleukin 10 in specific immunotherapy. J Clin Invest 1998; 102:98-106. clearly indicate that the GOS/FOS prebiotic mixture at a concentration of 0.8 g/100 ml influences the entire flora to develop in a way similar to that found in breast-fed infants.
