**7. Probiotics and necrotizing enterocolitis**

Necrotizing enterocolitis (NEC) is a serious anoxic and ischemic disease particularly affecting premature newborns, affecting almost the ileo-colic area, with bacteria

Intestinal Microbial Flora – Effect of Probiotics in Newborns 13

respiratory distress, surgery), neonatal research priorities on the prevention and treatment of sepsis in NEC and bronchopulmonary dysplasia (CLD) (Weizman & Alsheikh, 2006).

In view of the role of mediators of inflammation in CLD and in sepsis is therefore important to modulate the immune response in these young patients. Some studies have shown that probiotics can alter the intestinal microflora and reduce the growth of pathogenic microorganisms in the intestines of preterm infants, decreasing the incidence of necrotizing enterocolitis and sepsis. Moreover, a study performed in rats with immune deficiency has shown that the administration of LGG reduced the risk of colonization and sepsis by

One of our retrospective study, performed in 2002 at the University of Catania TIN, showed that supplementation from birth for at least 4-6 weeks of a symbiotic (lactogermine plus 3.5 x109 ucf / day) decreased the incidence and intensity of gastrointestinal colonization of Candida, and subsequently its related infections in a group of preterm infants. Another randomized study on 80 preterm infants has confirmed that the administration of LGG (at a dose of 6 billion cfu / day) from the first day of life for a period of six weeks

Newborns submitted to greater surgical interventions (esophageal atresia, hernia diaframmatica, intestinal malformations) have an increased risk of bacterial and/or mycotic infections due to the use of drains, central venous catheter, NPT, persistent nose-gastric

In a recent study that we presented at ESPHGAN, we demonstrated that surgical infants admitted to our NICU and supplemented with probiotics have a reduced risk of bacterial

In another recently published study on preterm infants, the use of probiotics appeared to be effective in the prevention of both bacterial and mycotic infections, in the attenuation of gastrointestinal symptoms and in a more rapid weaning from total parenteral nutrition with a reduction in the central venous catheter time and the number of days in hospital. These results were evident both in a group of preterm newborns and in a group of surgical

Two studies have examined the effect in adults of a combined multi-strain probiotic and multivitamin/mineral supplement containing L. gasseri, B. longum and B. bifidum on the incidence, duration and severity of common cold infections and aspects of immune function (de Vrese et al, 2006; Winkler et al, 2005). Both studies found a reduction in severity and duration, as well as enhanced expression of immune cells, while only Winkler et al. (2005) found a reduction in incidence. The major difference between studies is dose—the same probiotic strains were used for both, as well as the same assessment methods for the illness—suggesting that although the dose used by de Vrese et al. (2006) (5 9 107 CFU) was enough to attenuate symptoms and duration, a higher dose such as that used by Winkler et al. (2005) (5 9 108 CFU per day) was needed for prevention of infections. The lower dose may promote a systemic immune response sufficient to reduce severity and duration but not incidence, while the higher dose may stimulate systemic immunity via the mechanism of

and *Candida* infections and an improved clinical outcome (Figure 1) (Betta et al, 2007)

reduced the fungal enteric colonization with no side effects (Romeo et al, 2011).

probe that can be the cause of serious sepsis and pneumonias.

newborn treated with a supplementation of probiotics (Figure 2).

**9. Probiotics and respiratory tract infections (RTI)** 

Candida.

proliferation, production of gas inside gastric walls (cystic pneumatosis), associated with edema and inflammation. Its incidence rate is 1-3 cases for 1000 newborns, with a mortality rate ranging between 10-50%. The prematurity is the most important risk factor, as well as the low birth weight (< 1500 gr). This risk increases after the colonization or the infection of pathogens such as Clostridium, Escherichia, Klebsiella, Salmonella, Shigella, Campylobacter, Pseudomonas, Streptococcus, Enterococcus, Staphylococcus aureus and coagulase negative Staphylococcus. Other factors that can increase its incidence are the intestinal immaturity, the decrease of the intestinal motility, the increase of permeability to macromolecules and the excessive volume of milk. Certainly breast feeding represents a protective factor, as it is shown by the decreased incidence of NEC in breast-fed infants. Moreover literature data supporting the benefits of probiotics are increasing in the last decades.

The role of intestinal micro-organisms has been largely described, even if it is still not clear. Advances in molecular biology and intestinal microbiology allow a better characterization of the intestinal microbiota in children affected by NEC. Nowadays, literature data describe different methods of characterization of the microbic genotype and of identification of its genes, expression of the specific proteins and production of metabolites. The application of these techniques on bioptic samples of infected and non-infected subjects could better the comprehension of the persistence of NEC in premature newborns. Deshpande et al. (2007) published a meta analysis that confirms the benefit of probiotic supplements in reducing death and disease in preterm newborns.

The mechanism of action of probiotics in the protection of NEC seem to be the increased production of anti-inflammatory cytokines, blockage of the passage of bacteria and their products through the mucose, competitive action with some pathogen groups, modification of the response of the host towards microbial products, improving the enteral nutrition, decreasing the duration of the parenteral nutrition, responsible for late sepsis.

Different studies highlight that the supplementation of probiotics reduces the risk of NEC. In the most recent literature, the study of Bin-Nun et al. (2005) showed a lower frequency of serious diseases in newborns with a low birth weight when in their feeding was added a probiotic mixture. Desphande's meta analysis, published in Lancet in 2007, showed the same results. As a matter of fact the first studies on probiotics in premature children were leaded in order to reduce the incidence of NEC in this group of children.
