Faecal SIgA secretion in infants fed on pre- or probiotic infant formula

A. Bakker-Zierikzee, E.A.F. van Tol, H. Kroes, M.S. Alles, F.J. Kok, J.G. Bindels

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Abstract

Secretory immunoglobulin A (SIgA) plays an important role in the defence of the gastrointestinal tract. The level of faecal SIgA antibody is associated with increased neutralization and clearance of viruses. Formula-fed infants who lack the transfer of protective maternal SIgA from breast milk may benefit from strategies to support maturation of humoral immunity and endogenous production of SIgA. We aimed at studying the effects of standard, prebiotic and probiotic infant formulas on the faecal SIgA levels. At birth, infants of whom the mother had decided not to breastfeed were allocated to one of three formula groups in a randomized, double-blind fashion. Nineteen infants received standard infant formula; 19 received prebiotic formula containing a specific mixture of 0.6 g galacto-oligosaccharides (GOS)/fructo-oligosaccharides (FOS)/100 ml formula and 19 received probiotic formula containing 6.0 × 109 cfu Bifidobacterium animalis/100 ml formula. Faecal samples were taken on postnatal day 5, day 10, wk 4 and every 4 wk thereafter until wk 32. SIgA in faeces was determined by an enzyme-linked immunosorbent assay. During the intervention, infants fed on prebiotic formula showed a trend towards higher faecal SIgA levels compared with the standard formula-fed infants reaching statistical significance at the age of 16 wk. In contrast, infants fed on the probiotic formula showed a highly variable faecal SIgA concentration with no statistically significant differences compared with the standard formula group. Formula-fed infants may benefit from infant formulas containing a prebiotic mixture of GOS and FOS because of the observed clear tendency to increase faecal SIgA secretion. Adding viable B. animalis strain Bb-12 to infant formula did not reveal any sign for such a trend. Secretory immunoglobulin A (SIgA) is one of the most abundant immunoglobulin in the human body and is the predominant immunoglobulin in mucosal surfaces. SIgA plays a key role in the gastrointestinal defence mechanism against dietary and microbial antigens. It inhibits adherence and invasion of potentially harmful antigens into mucosal tissues and neutralizing toxins and virulence factors from microbial pathogens (1). It is well established that the level of faecal SIgA antibody correlates with higher virus-neutralizing capacity and increased viral clearance (2). IgA deficiency in humans is one of the most common immunodeficiencies and is associated with frequent gastrointestinal infections (3). There is accumulating evidence that the intestinal SIgA production is highly influenced by the intestinal microflora. Indeed, the development of the IgA-producing plasmablasts (intermediate stage of the development of a B-lymphocyte into IgA-producing plasma cell) in the intestinal mucosa seems to be affected by components of the intestinal microflora (4). During the first few weeks after birth, the mucosal humoral immunity is not in a mature state. Passive immunity in this phase is provided by breast milk, which contains high levels of SIgA and antimicrobial peptides. SIgA in breast milk are mainly directed against the mother's previous and current gut microflora (5). Breast milk SIgA protects the maternal mammary gland against mastitis, protects the neonatal mucosa against early exposure to microbes and limits bacterial translocation. In breast milk, SIgA levels are highest during the first days after birth (human colostrum contains 2¿5 mg SIgA/ml) and then gradually decrease to 0.5¿1 mg/ml (6). Although many factors may influence SIgA survival in the large intestine, measuring SIgA levels in faeces gives a good representation of the amount available in the colon (7). In the first 2¿4 wk of life, the concentration of IgA in faeces of breast-fed infants is substantially higher compared to that found in formula-fed infants in whom SIgA is basically undetectable (8). Between 4 wk and 6 months of life, faecal IgA concentrations in both breast-fed and formula-fed infants converge towards similar levels. At age 1¿2 yr, when weaning is completed, the production of SIgA reaches adult levels (9). It is generally recognized that intestinal microflora may play an active role in the ontogeny of the newborn's immune response. Studies performed in germ-free animals showed that colonization leads to the development of the gut-associated lymphoid tissue, including SIgA secretion in the intestine (10, 11). Moreau and Baforiau-Routhiau have shown that in particular bifidobacteria in the infant's intestine are important for the synthesis of IgA against viral enteropathogens. Therefore, they suggested that foods promoting bifidobacteria in the intestine could be instrumental in stimulating endogenous SIgA production and hence promote resistance in infants (12). Although the mechanism of immune stimulation by bifidobacteria is largely unknown, it is thought that the cell walls of Gram-positive bacteria, which are rich in peptidoglycans, may play a role. Both prebiotics and probiotics change the intestinal microflora by increasing the numbers of bifidobacteria and lactobacilli. Bifidobacteria and lactobacilli have various beneficial effects in health and disease, including maintenance of intestinal barrier integrity and mucoprotection, stimulation of protective immune responses and protection against harmful pathogens. During the last decade, interest on the immune effects of probiotics has increased markedly. Experimental studies showed that probiotics have strain-specific effects on immunity, for instance in the prevention or treatment of allergic disease. The reported effects of probiotics include enhancement of gut barrier function and induction of regulatory and pro-inflammatory immune responses (13). Additionally, several studies reported that supplementation of food with prebiotics or probiotics can increase SIgA response to viruses and bacteria. However, most of these studies were performed in animals or in vitro and the mechanisms for this immune stimulation are largely unknown (14¿18). As infants not receiving breast milk have lower SIgA levels during the first months of life, they would potentially benefit from strategies to support maturation and production of mucosal SIgA. Therefore, we studied the effects of infant formula with added probiotics or prebiotics on the faecal SIgA levels in infants. We hypothesized that infants on probiotics or prebiotics will have higher levels of total faecal SIgA compared with infants fed on a standard, unsupplemented infant formula
Original languageEnglish
Pages (from-to)134-140
JournalPediatric Allergy and Immunology
Volume17
Issue number2
DOIs
Publication statusPublished - 2006

Keywords

  • lactic-acid bacteria
  • human-milk
  • immunity
  • iga
  • fructooligosaccharides
  • bifidobacterium
  • antibodies
  • serum
  • responses
  • children

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    Bakker-Zierikzee, A., van Tol, E. A. F., Kroes, H., Alles, M. S., Kok, F. J., & Bindels, J. G. (2006). Faecal SIgA secretion in infants fed on pre- or probiotic infant formula. Pediatric Allergy and Immunology, 17(2), 134-140. https://doi.org/10.1111/j.1399-3038.2005.00370.x