By Marko Kalliomäki, Seppo Salminen, Heikki Arvilommi, Pentti Kero, Pertti Koskinen, Erika Isolauri

Condensed Version Of Original Landmark Lancet Article

More than half the developing countries have allergy problems in their children.(1)

The authors propose that specific microbes in the gut microflora are more important than sporadic infections in allergy prevention. Gastrointestinal microflora promote potentially antiallergenic processes:

• T-helper-1-type immunity;(2)
  

• Generation of transforming growth factor (3,4) which has an essential role in suppression of T-helper-2-induced allergic inflammation(5) and induction of oral tolerance;(6) and
  

• IgA production,(7) an essential component of mucosal immune defence. The gut microflora might therefore be a major postnatal counter-regulator of the universal T-helper-2-skewed immune system in fetuses and neonates.

Probiotics have been previously proven effective in allergic inflammation (4) and food allergy.(8)

Confrontation between microbes and their antigens in the gastrointestinal tract begins instantly after birth, and the viable cells of fully established gut microflora outnumber those of the human host by a factor of ten. (9) Consequently, gastrointestinal microbes are the earliest and biggest stimulus for development of gut-associated lymphoid tissue.

Probiotics also enhance gut-specific IgA responses,(10) which are often defective in children with food allergy.(11)

They also help to promote gut barrier function and restore normal gut microecology,(9) alterations in which have been shown in allergic individuals.(12)

Some probiotics alleviate changes related to allergic inflammation in vitro and in vivo. (5, 12, 13)

Use of probiotics in allergy prevention is further lent support by results of studies (14,15) showing that oral lactobacilli in atopic children enhance transforming growth factor ß and interleukin (4) production in vivo.

Findings from clinical and experimental studies (6,16) suggest that these anti-inflammatory cytokines have a crucial role, possibly more essential than that of T-helper-1-type inducers, in prevention and treatment of atopy and atopic diseases.

Thus, specific strains in indigenous gut microflora have profound effects on the physiology and immunology of the host.

At birth, the human gastrointestinal tract is sterile, but in the first months and years of life a rapid sequential colonisation occurs until a stable indigenous gut microflora is established.(9)

Simultaneously, the T-helper-2-dominant immunity of newborn babies is intensified in atopic individuals, with the subsequent expression of atopic disease.(17)

In support of an essential role for indigenous gut microflora in this process, a reduced ratio of bifidobacteria to clostridia in early gut microflora precedes the development of atopy and atopic disease.(18)

Dietary antigens also strongly affect the neonatal gastrointestinal system. Results from work in animals indicate that these antigens might provoke atopic-type immunity at mucosal and systemic level.(19)

Therefore, treatment for counter-regulation of allergy must work in infancy, and preferably in the first encounters with dietary antigens. Probiotics are appropriate for the task, not only with respect to timing, but also in their ability to reduce dietary antigen load by degradation and modification of macromolecules.(20)

This process of antigen degradation is necessary in development of non-responsiveness to dietary antigens.(21)

Our results suggest that gut microflora have unique, yet largely unexplored, endogenous immunomodulatory properties. These properties might be indispensable in the fight against the increasing frequency of atopic, and possibly other, immunological diseases.

The Lancet 2001; 357: 1076-79

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