*3.1.3 Conclusion*

*Prebiotics and Probiotics - Potential Benefits in Nutrition and Health*

prevention of colic, especially in formula-fed infants [34].

late-onset sepsis and necrotizing enterocolitis or death.

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

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

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

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

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

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

atopic dermatitis in infants but not of other types of allergies [43–45].

**6**

of infections.

microbiota [23, 50].

and in infants with a high risk of allergy.

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 quality evidence on their efficacy [55].
