Food hypersensitivity and allergy are prevalent and represent a substantial health problem that may be increasing in developed countries (Burr 1989; Halken 2004; Prescott 2005; Schultz Larsen 1996). Genetic susceptibility plays a large role in the development of food allergy. Although less than half of those who develop childhood allergic disease have a first degree family history of allergy, the risk of development of allergic diseases increases substantially with family heredity. Approximately 10% of children without an allergic first degree relative develop allergic disease, compared to 20 ‐ 30% with single allergic heredity (parent or sibling) and 40 ‐ 50% with double allergic heredity (Arshad 2005; Bergmann 1997; Hansen 1993; Kjellman 1977). The manifestations of allergic disease are age dependent. Infants commonly present with symptoms and signs of atopic eczema, gastrointestinal symptoms and recurrent wheezing. Asthma and rhinoconjunctivitis become prevalent in later childhood. The patterns of sensitization to allergens tends to follow a characteristic pattern, with sensitization to food allergens in the first two to three years of life, then indoor allergens (e.g. house dust mite and pets) and subsequently outdoor allergens (e.g. rye and Timothy grass). The cumulative prevalence of allergic disease in childhood is high, with up to 7 ‐ 8% developing a food allergy, 15 ‐ 20% atopic eczema, and 31 ‐ 34% developing asthma or recurrent wheezing. Of these, 7 ‐ 10% will continue to have asthma symptoms beyond five years of age (Halken 2004). Food hypersensitivities affect approximately 6% of infants less than three years of age, with prevalence decreasing over the first decade (Sampson 2004; Osterballe 2005).

A major focus of current research is the mechanisms for development of immune tolerance and allergen sensitization in the fetus and newborn and primary prevention strategies. This review focuses on the evidence for use of probiotics in infants for the prevention of food hypersensitivity and allergy. A separate review will examine the effects of prebiotics compared to no prebiotics in infants for prevention of allergy and food hypersensitivity. Probiotics are live bacteria that colonize the gastrointestinal tract and provide a health benefit to the host. They have been defined as "living micro‐organisms which upon ingestion in certain numbers exert health benefits beyond inherent general nutrition" (Guarner 1998). Probiotics have been demonstrated to have anti‐inflammatory properties, associated with changes in cytokine expression with the potential to facilitate T1‐helper cell immune response (Heller 2003; Sudo 1997) that could inhibit the development of allergic T2‐helper cell response and allergic (IgE) antibody production. Benefits from the use of probiotic bacteria have been found in systematic review of randomised trials (Allen 2004) for the treatment of infectious diarrhoea. Several randomised studies have now demonstrated efficacy from use of probiotics in infants with active eczema (Majamaa 1997; Isolauri 2000; Rosenfeldt 2003), although not all studies have shown conclusive benefits (Viljanen 2005). Although rare, anecdotal case reports have described infants with sepsis from lactobacillus attributable to probiotic supplementation (Hammerman 2006).

An altered microbial exposure may be partly responsible for the increase of allergic diseases in populations with a western lifestyle (Holt 1997). Differences in intestinal microflora are found in infants delivered by caesarean section compared to those delivered vaginally, and in breast fed versus formula fed infants (Agostoni 2004). Breast feeding promotes the colonization of bifidobacteria and lactobacilli that inhibit growth of pathogenic microorganisms and compete with potentially pathogenic bacteria for nutrients and epithelial adhesion sites. The gastrointestinal flora may modulate mucosal physiology, barrier function and systemic immunologic and inflammatory responses (Agostoni 2004; Sudo 1997). Food allergy is a manifestation of an abnormal mucosal immune response to ingested dietary antigens (Sampson 2004 ). The gastrointestinal barrier is a complex physiochemical barrier and cellular barrier. However, some ingested food antigens are absorbed. The efficiency of this gastrointestinal barrier is reduced in the newborn period. Perinatal risk factors reported for asthma and / or allergy have included prematurity (Bernsen 2005; Jaakkola 2004; Raby 2004) and fetal growth restriction (Bernsen 2005), both of which are associated with an immature and potentially injured gastrointestinal mucosal barrier. The composition of the intestinal microflora may be different in those with atopic eczema, and such differences may precede the development of eczema. The most consistent finding in such studies is a reduced proportion of bifidobacteria species in the faeces of infants with eczema (Bjorksten 2001; Murray 2005) and atopic sensitization (Kalliomaki 2001), but not in the faeces of children with symptoms of asthma (Murray 2005). The recognition of the importance of intestinal flora has led to the development of strategies aimed at manipulating bacterial colonization in formula fed infants, including the use of prebiotics and probiotics.

Prevention of allergy is divided into primary prevention, the prevention of immunological sensitization (development of IgE antibodies); and secondary prevention, the prevention of allergic disease following sensitization (Asher 2004). A substantial proportion of infants who develop sensitization will not go on to have clinical manifestations of allergy or food hypersensitivity (Halken 2004). This review will focus on the prevention of clinical allergy (including asthma, eczema and allergic rhinitis) and food hypersensitivity, not just sensitization (IgE responses). As the risk of allergy and food hypersensitivity is affected by heredity, subgroup analysis will examine the effect of probiotics in populations of infants at high risk of allergy or food hypersensitivity separately to infants at low risk or not selected on the basis of heredity. As breast feeding promotes the colonization of bifidobacteria and lactobacilli (Agostoni 2004), subgroup analysis will examine the effect of probiotics in human milk fed infants separately to probiotics in formula fed infants. Prebiotics are nondigestible food components that beneficially affect the host by selectively stimulating the growth or activity of bacteria in the colon. They can be added to infant formula. In infants, studies have demonstrated significant increases in faecal bifidobacteria in response to formula supplementation with oligosaccharides (Boehm 2002; Moro 2002; Moro 2006; Schmelzle 2003; Decsi 2005), with one study also demonstrating an increase in lactobacilli (Moro 2002). Subgroup analyses will be performed to determine if the effect of probiotics is modified by the addition of a prebiotic to infant feeds.