**5. Symbiotics**

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

been incorporated to some infant formula [60].

*4.1.2 Prevention and treatment of infant disorders*

the frequency of defecations [32, 62].

especially respiratory infections [60].

to be similar to those found in breastfed infants.

safety and efficacy of prebiotic supplementation.

decreases with prebiotics.

*4.1.1 Safety*

2′-flucosyllactose, a HBM oligosaccharide, was recently synthesized and has

Formulae fortified with prebiotics do not raise safety concerns with regard to growth and adverse effects. [19]. Infant formulae containing HBM oligosaccharides have proven to be safe and well tolerated, and synthetic oligosaccharides have demonstrated to have similar effects to those of HBM oligosaccharides [60].

There is solid evidence that infant formula containing some prebiotics is associated with less-consistent feces and a higher frequency of defecation [61]. However, inconsistent evidence has been obtained on the association between prebiotics and

The use of prebiotic-fortified formulae has been associated with a lower risk for intestinal and respiratory infections [63, 64] and an increase in fecal secretory IgA levels [65]. By contrast, they have not been proven to exert any effects on humoral and cellular immunity [66]. In general terms, there is no conclusive evidence supporting that supplementation of infant formulae with prebiotics exerts any protective effects against infections, colic, crying/irritability, regurgitation, or vomiting [19, 32]. Fortification with 2′-flucosyllactose does seem to improve infant immunity, as it has been reported to be related to a lower incidence of infections,

GOS:FOS mixtures favor the growth of bifidobacteria and lactobacilli in the feces of infants receiving fortified formulae. However, they have a limited effect on the reduction of pathogenic bacteria [19]. Yet, some studies suggest that prebiotics reduce pathogenic micro-organism concentrations, while the infant is receiving a formula supplemented with oligosaccharides [67]. A number of studies [25, 32, 62] have failed to demonstrate that bifidobacteria, lactobacilli, or pathogen count

Other studies have shown similarities between the bifidogenic effect of prebiotic-fortified formulae and HBM, as compared to non-fortified formulae [59, 68, 69]. Indeed, prebiotics have been reported to have special effects on some bifidobacteria species such as *Bifidobacterium breve*. Thus, fecal *Bifidobacterium breve* concentrations in infants fed with a fortified formula have been documented

Although prebiotic-supplemented formulae are thought to prevent eczema in infants at high risk of developing allergies [43, 63, 70], there is no sufficient evidence on the role that prebiotics play in the prevention of eczema, atopic dermatitis, or food hypersensitivity [71, 72]. A partially hydrolyzed formula containing specific prebiotics has been reported to generate a gut microbiota similar to that of breastfed infants. A potential link between microbial activity and eczema onset was identified, which could suggest a suboptimal implementation of gut microbiota in specific developmental stages of infants at high risk of developing allergy [73].

ESPGHAN Committee on Nutrition does not recommend routine use of infant formulae supplemented with prebiotic. In agreement with the American Academy of Pediatrics, they recommend that further studies are conducted to assess the

**8**

*4.1.3 Conclusion*

Symbiotics are mixtures of probiotics and prebiotics that beneficially affect the host by improving the survival and implantation of the probiotic bacteria and stimulate the activity of the host's endogenous bacteria [56]. Symbiotics are believed to act synergistically to increase the overall gut health by offering more benefits than the use of either a probiotic or prebiotic agent alone. Considering a huge number of possible combinations, the application of symbiotics for the modulation of intestinal microbiota in humans seems promising [74]. A disadvantage to using symbiotics is that it is difficult to predict the selectivity and specificity of each of the components and what the resulting mechanisms of action will be.

Limited data have been provided on concomitant prebiotic and probiotic supplementation of infant formulae. The few studies carried out with symbiotics [19, 32, 75] revealed that symbiotics: (a) do not exert effects on growth; (b) do not reduce the incidence of digestive disorders (colic, regurgitation, crying, vomiting, to name a few) or infections; (c) increase the frequency of daily defecations but do not influence fecal consistency; and (d) no data are available on their effects on the composition of gut microbiota or on immune response.

There is no conclusive evidence on the effects of supplementation of infant formula with symbiotics. Therefore, ESPGHAN Committee on Nutrition does not recommend routine use of infant formula fortified with symbiotics.
