**4. Probiotics and gastrointestinal disorders**

The presence of Bifidobacteria in artificial milk can contribute to the induction of a significant increase of Bifidobacteria in the intestinal tract, promotes the development of a protective microflora, similar to that one of the breast- fed newborn, contributes to the modulation of immune-defenses, giving them a major efficiency (Langhendries et al, 1995; Fukushima et al, 1998).

Intestinal Microbial Flora – Effect of Probiotics in Newborns 9

As previously mentioned, the sequence of bacterial intestinal colonization of neonates and young infants is important in the development of the immune response. Recognition by the immune system of self and nonself, as well as the type of inflammatory responses generated later in life, are likely affected by the infant's diet and acquisition of the commensal

During pregnancy, the cytokine inflammatory-response profile of the fetus is diverted away from cell-mediated immunity (T-helper 1 [Th1] type) toward humoral immunity (Th2 type). Hence, the Th2 type typically is the general immune response in early infancy. The risk of allergic disease could well be the result of a lack or delay in the eventual shift of the predominant Th2 type of response to more of a balance between Th1- and Th2-type

Administration of probiotic bacteria during a time period in which a natural population of lacticacid– producing indigenous intestinal bacteria is developing could theoretically influence immune development toward more balance of Th1 and Th2 inflammatory responses (Majamaa & Isolauri, 1997). The intestinal bacterial flora of atopic children has been demonstrated to differ from that of nonatopic children. Specifically, atopic children have more Clostridium organisms and fewer Bifidobacterium organisms than do nonatopic study subjects ( Björkstén et al, 1999; Klliomaki et al, 2001), which has served as the rationale for the administration of probiotics to infants at risk of atopic diseases, particularly for those

In a double-blinded RCT, LGG or a placebo was given initially to 159 women during the final 4 weeks of pregnancy. If the infant was at high risk of atopic disease (atopic eczema, allergic rhinitis, or asthma), the treatment was continued for 6 months after birth in both the lactating woman and her infant (Kalliomäki et al, 2003). A total of 132 mother-infant pairs were randomly assigned to receive either placebo or LGG and treated for 6 months while breastfeeding. The primary study end point was chronic recurrent atopic eczema in the infant. Atopic eczema was diagnosed in 46 of 132 (35%) of these study children by 2 years of age. The frequency of atopic eczema in the LGG-treated group was 15 of 64 (23%) versus 31 of 68 (46%) in the placebo group (RR: 0.51 [95% CI: 0.32– 0.84]; P = .01). The number of mother-infant pairs required to be treated with LGG to prevent 1 case of chronic recurrent atopic eczema was 4.5. By 4 years of age, eczema occurred in 26% of the infants in the group treated with LGG, compared with 46% in the placebo group (RR: 0.57 [95% CI: 0.33– 0.97]; P =.01). However, only 67% of the original study group was analyzed at the 4-year follow-up. These results support a preventive effect for giving a probiotic to mothers late in pregnancy and to both mothers and infants during the first 6 months of lactation for the prevention of

Conversely, Taylor et al (2007) found that probiotic supplementation did not reduce the risk of atopic dermatitis in children at high risk with the report of some increased risk of subsequent allergen sensitization. As concluded in a review by Prescott and Björkstén (2007) and in a 2007 Cochrane review (Osborn & Sinn, 2007) despite the encouraging results of some studies, there is insufficient evidence to warrant the routine supplementation of probiotics to either pregnant women or infants to prevent allergic diseases in childhood. Explanations for varied study results include host factors such as genetic susceptibility,

**5.1 Use of probiotics for prevention of atopic diseases** 

atopic eczema in infants who are at risk of atopic disease.

responses (Neaville, 2003).

who are formula fed.

intestinal bacterial population superimposed on genetic predisposition.

In early 2002, the United States Food and Drug administration accepted a "generally regarded as safe (GRAS) the use of *Bifidobacterium lactis* and *Streptococcus thermophilus* in formula milk for healthy infants aged 4 months or more" (Hammerman et al, 2006).

The clinical efficacy of probiotics in the prevention and treatment of infectious disease in infancy has most comprehensively been documented in diarrhoeal disease. *Lactobacillus* GG or *Lactobacillus reuteri* (ATCC 55730) supplementation has been demonstrated to be effective in the prevention of acute infantile diarrhoea in different settings. *Lactobacillus* GG has also been reported to significantly reduce the duration of acute diarrhoea and the duration of rotavirus shedding after rotavirus infection. Bifidobacteria have also shown promising potential in preventing both nosocomial spread of gastroenteritis and diarrhoea in infants in residential care settings. Meta-analyses of double-blind, placebo-controlled clinical trials have concluded that probiotics, particularly *Lactobacillus* GG, are effective in treatment of acute infectious diarrhoea in infants and children. Probiotics appear also to have some protective effect against antibiotic-associated diarrhoea and acute diarrhoea in children, but the heterogeneity of the available studies precludes drawing firm conclusions (Vanderhoof, 2000).
