Probiotics in the prevention of allergy
Until recently, only one published study addressed the role of probiotics in primary prevention of allergic diseases. This study by Kalliomaki and colleagues reported that daily treatment of high-risk children (parental of sibling allergy) with Lactobacillus rahmnosus GG in their first 6 months of live halved the incidence of eczema at age 2 years (1). This risk reduction was still present at the follow-up of 4 and 7 years (2, 3). In contrast to this reduction in the incidence of eczema, no effect on atopic sensitization was found. The strength of the reported effect was remarkable, however some concerns have been raised about the heterogeneity of the intervention group. Formula-fed infants received the probiotics directly, while the mother took the probiotics if the baby was breastfed.
In the January issue of the Journal of Allergy and Clinical Immunology, two new placebo-controlled RCT’s have been published on the use of probiotics in the prevention of allergy.
The first paper described a trial conducted in Perth, Australia (4). 231 high-risk (maternal allergy) newborns received either Lactobacillus acidophilus (LAVRI-A1) or placebo daily for the first six months of life. This study showed no risk reduction in eczema at age 6 and 12 months. In contrast probiotic therapy was associated with an increased risk of atopic sensitisation alone and in combination with eczema (atopic eczema).
The second paper discussed a trial conducted in the suburban area of Helsinki, Finland (5). 1223 pregnant women carrying high-risk (parental allergy) children were randomised to receive a multispecies probiotic (Lactobacillus rahmnosus GG (ATCC53103), L. rahmnosus LC705 (DSM 7061), Bifidobacterium breve Bb99 (DSM 13692) and Propionibacterium freundenrechii spp. Shermanii JS (DSM 7061) or a placebo 2 to 4 weeks prior to delivery. Their infants received the same probiotic plus galacto-oligosaccharides or placebo for the first six months of life. In this study, probiotic therapy showed to reduce eczema by age 2 years, and especially reduced atopic eczema (eczema + positive SPT)
Both studies addressed the comments made by the criticasters of the Kalliomaki-study.
First of all, the probiotic or plabo were directly administered to all infants. Furthermore, stool samples were cultured in both studies for the quantification of lactobacilli and bifidobacteria. Administration of probiotics significantly increased the colonization rate of lactobacilli in the Perth study (L. acidophilus), and the colonization rates and counts of bifidobacteria and lactobacilli in the Helsinki study (multispecies product).
There were however also some differences in the study designs, which might explain there opposite findings. Obviously the different probiotics used in the two studies (L. acidophilus versus a multispecies product plus oligosaccharides) is a logical explanation for the different study results, as it is well known that every probiotic strain has unique immunomodulatory effects. However, another difference between the studies is that in the Perth study supplementation began in the first days of the infant’s life, whereas in the Helsinki study mothers commenced supplementation already during pregnancy (comparable to the Kalliomaki study). This could imply a direct effect in utero rather than any effect on postnatal colonization. Although it seems unlikely that supplementation for only a few weeks in the antenatal period alone would account for such significant differences in study outcomes, this remains a possibility.
In conclusion, prevention of atopic eczema in high-risk infants appears possible by modulating the gut microbiota with probiotics (and prebiotics). The probiotic strains used, but potentially also the timing of supplementation (antenatal and/or postnatal), appear key determinants of the success of the intervention.
1. Kalliomaki M, Salminen S, Arvilommi H, Kero P, Koskinen P, Isolauri E. Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial. Lancet 2001;357:1076-9.
2. Kalliomaki M, Salminen S, Poussa T, Isolauri E. Probiotics during the first 7 years of life: A cumulative risk reduction of eczema in a randomized, placebo-controlled trial. J Allergy Clin Immunol 2007;119:1019-21.
3. Kalliomaki M, Salminen S, Poussa T, Arvilommi H, Isolauri E. Probiotics and prevention of atopic disease: 4-year follow-up of a randomised placebo-controlled trial. Lancet 2003;361:1869-71.
4. Taylor AL, Dunstan JA, Prescott SL. Probiotic supplementation for the first 6 months of life fails to reduce the risk of atopic dermatitis and increases the risk of allergen sensitization in high-risk children: a randomized controlled trial. J Allergy Clin Immunol 2007;119:184-91.
5. Kukkonen K, Savilahti E, Haahtela T, Juntunen-Backman K, Korpela R, Poussa T, et al. Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: a randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol 2007;119:192-8.