*3.1.2 Prevention and treatment of infant disorders*

Conflicting results have been obtained regarding the effects of probiotics on the composition of fecal microbiota. A decrease in bifidobacteria and enterobacteria concentrations has been reported with respect to controls [25, 26]. Also, no differences have been observed in lactobacillus and bacteroides. By contrast, Maldonado et al. [27] reported an increase in fecal bifidobacteria and lactobacilli concentrations in infants fed with a formula supplemented with *Lactobacillus fermentum* CECT 5716. Also, no differences were found in other bacteria strains. Evidence has been provided that a formula containing *Bifidobacterium lactis* can influence the composition, stability, and function of gut microbiota in low-weight newborns [28].

The literature reports that probiotic supplementation of formula beyond early infancy can produce a decrease in the use of antibiotics and incidence of diarrhea, colic, and/or irritability. Yet, the variety of methods, type and dose of probiotics, and duration of interventions hinders that conclusive data can be obtained on clear clinical effects of probiotic-supplemented formulae in infants younger than 4 months [19].

In general, there is no consistent evidence supporting that supplementation of follow-on formula with probiotics has protective effects against infectious diarrhea [19]. Yet, a reduction has been reported in the duration and number of episodes of diarrhea associated with the use of probiotic-supplemented formulae [27, 29–31].

A systematic review conducted by Mugambi et al. [32] of controlled, randomized trials did not reveal that supplementation had any effects on infectious diarrhea, colic, crying/irritability, regurgitation, or vomiting. No beneficial effects were documented on either crying or irritability in the review by ESPGHAN Committee on Nutrition. A study that was not included in ESPGHAN study showed that colic symptoms substantially improved with the administration of *Lactobacillus reuteri* DSM 17938 in breastfed infants [33]. There is no sufficient evidence, however, supporting routine supplementation with probiotics for the treatment or prevention of colic, especially in formula-fed infants [34].

In a review on the effects of a variety of immunonutrients in the prevention of necrotizing enterocolitis [35], the authors gathered sufficient data supporting supplementation of infant formulae with probiotics. Several meta-analyses combined these randomized controlled trials and observational studies demonstrated that the use of probiotics was beneficial for the prevention of severe necrotizing enterocolitis, late-onset sepsis, and all-cause mortality in very-low-birth-weight infants, as well as the time to achieve full enteral feeding in preterm infants [36–38]. By contrast, no differences were observed in a multicenter study involving 1315 preterm newborns fed with a hydrolyzed formula supplemented and nonsupplemented with the probiotic *Bifidobacterium breve* BBG-001 [39]; the results of this trial provide no evidence of benefit of this probiotic intervention in reducing late-onset sepsis and necrotizing enterocolitis or death.

In relation to respiratory infections, limited available evidence from randomized controlled trials showed that formula supplementation with the probiotics studied is not associated with a reduction in the duration or risk of respiratory infections [19, 32]. A number of studies on formulae supplemented with different probiotic bacteria [30, 27, 40, 41] have shown a significant reduction in the number of upper airway tract infections in infants fed with these formulae. A study on *Lactobacillus fermentum* CECT 5716 [27] reports a significant 30% reduction in the total number of infections.

Significant reductions have been documented in the incidence of influenza and respiratory symptoms in several studies, where *Lactobacillus fermentum* CECT 5716 was administered in combination with anti-influenza vaccine [42]. This effect is explained by increased levels of NK cells and T-helper and T-cytotoxic lymphocytes.

Sufficient evidence has not been published supporting the beneficial effects of supplementation of infant formulae with probiotics on allergies. Several metaanalyses, however, have shown that the use of probiotics reduces the incidence of atopic dermatitis in infants but not of other types of allergies [43–45].

Evidence has been published that dietary treatment with a extensively hydrolyzed formula containing *Lactobacillus rhamnosus* GG is associated with a higher rate of acquisition of tolerance in infants allergic to cow's milk proteins, as compared to infants treated with a non-supplemented hydrolyzed formula [46, 47]. A relationship has been documented between dysbiosis in gut microbiota composition and the pathogenesis of cow's milk allergy [48, 49]. In addition, the administration of a hydrolyzed formula supplemented with probiotics reduces the incidence of other allergies and favors tolerance, as it changes the composition of infant's gut microbiota [23, 50].

Some studies suggest that gut microbiota alterations precede the development of the allergic phenotype. Therefore, probiotics could exert preventive and therapeutical effects [51]. The potential of some strains to favor Th1 and Th3 immune response against Th2 activity in patients with atopy can create the optimal conditions to redirect immune memory and reduce the risk of atopic disease. The Work Allergy Organization (WAO) [52] determined that probiotics confer health benefits in the prevention of eczema. Thus, WAO recommends the use of probiotics in pregnant or breastfeeding women whose infants have a high risk of developing allergies and in infants with a high risk of allergy.

**7**

*Probiotics and Prebiotics in Infant Formulae DOI: http://dx.doi.org/10.5772/intechopen.88609*

quality evidence on their efficacy [55].

they primarily contain 5-N-acetyl-neuraminic acid [58].

proliferation and differentiation of gut mucosal cells.

**4.1 Infant formulae supplemented with prebiotics**

component following lactose and lipids.

ESPGHAN Committee on Nutrition does not recommend the routine use of infant formulae supplemented with probiotics. However, the evidence obtained in recent studies suggests that infant formulae containing some specific bacteria strains can confer beneficial health effects. A large number of infant formulae currently available on the market contain probiotics, and several panels support their use provided that their safety and benefits for the health and development of the infant have been demonstrated [19, 53, 54]. The European Food Safety Authority (EFSA) supports the safety of formula supplementation with probiotic bacteria. Yet, EFSA recommends that further studies are conducted to obtain the highest

Prebiotics are defined as oligosaccharides refractory to the human digestive process with ability to stimulate and promote the growth and/or metabolism of bifidobacteria and lactobacilli in human gut [56]. More than 200 oligosaccharide complexes (neutral and cyclical oligosaccharides) have been identified in human breast milk [57]. Neutral oligosaccharides account for 70% of the total count and include the isomers lacto-N-tetraose, lacto-N-neotetraose, lacto-N-hexaose, monofucosyl-lacto-N-hexaose, and difucosyl-lacto-N-hexaose. Low levels of acidic oligosaccharides containing sialic acid or sulfate groups are present in HBM, and

Colostrum is composed of higher oligosaccharide concentrations (15–23 g/L),

Most of these oligosaccharides are non-absorbable and reach the colon, where they have different functions. Thus, they compete for membrane receptors with pathogenic bacteria and viruses in intestinal epithelium; they contribute to acidification via fermentation by colon bacteria; inhibit the growth of bacteroides, clostridia, and coliforms; promote lactobacilli and bifidobacteria growth; and stimulate

Cow milk oligosaccharide content is substantially lower than that of HBM, and infant formula supplementation with prebiotics with the purpose of obtaining their health benefits is well founded. At present, GOS and FOS combinations are used, and other HBM oligosaccharides have been recently incorporated to infant formulae.

The European Scientific Committee on Food approved prebiotic supplementation in infant and follow-on formulate up to a maximum of 0.8 g/100 ml to a GOS:FOS ratio of 9:1. By contrast, a systematic review on the safety and health effects of prebiotic-supplemented infant formulae conducted by ESPGHAN Committee on Nutrition [19] did not provide conclusive evidence due to variability

in the type and dose of the prebiotic used and period of intervention.

whereas mature HBM contents range from 1 to 10 g/L [59]. Oligosaccharides account for 8% of the total nutrient contents of HBM and are the third prevalent

the development of infant's immune system. A direct relationship has been documented between oligosaccharides and selectins, integrins, and other receptors, and they mediate leukocyte-endothelial cell interactions [59]. Fermentation of prebiotics by gut bacteria produces short-chain fatty acids, which exert a direct anti-inflammatory effect and promote intestinal barrier integrity by stimulating the

*3.1.3 Conclusion*

**4. Prebiotics**
