Eczema is a chronic, inflammatory skin condition that affects up to 20 per cent of children. It is characterized by varying degrees of redness and itching, mainly affecting the face, neck, and folds of the knees and elbows. Although eczema can present at any time throughout life, the age of onset for more severe or chronic eczema is typically before two years and often within the first six months of life. According to one study, 10.7 per cent of the total U.S. population, or 31.6 million Americans, meet the broad symptoms criteria for eczema, and associated costs may be as high as $1–4 billion.1
The health of our immune system begins during early development. It is important to incorporate healthy preventive strategies prenatally to ensure not only a healthy baby but also development into a health adult. The link with infantile eczema and ongoing allergy as been made – balancing the immune response is key to moderating allergy. Dr. Barry Ritz, who studied his PhD in Nutritional Immunology, highlights recent research supporting nutritional strategies, both prenatally and in the early months of an infant’s life, affecting eczema and possibly ongoing allergic response.
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What is Eczema?
Eczema is a chronic, inflammatory skin condition that affects up to 20 per cent of children. It is characterized by varying degrees of redness and itching, mainly affecting the face, neck, and folds of the knees and elbows. Although eczema can present at any time throughout life, the age of onset for more severe or chronic eczema is typically before two years and often within the first six months of life. According to one study, 10.7 per cent of the total U.S. population, or 31.6 million Americans, meet the broad symptoms criteria for eczema, and associated costs may be as high as $1–4 billion.1
The prevalence of allergic diseases among children, including eczema, has increased dramatically during the past few decades and continues to rise.2
Furthermore, childhood eczema is associated with the development of other allergic diseases later in life, including asthma,3 a phenomenon referred to as the Allergic March. As a result, there is considerable interest in identifying effective treatments for the prevention of eczema. One proposed treatment option that is being heavily studied is the use of probiotics.
Probiotics
Probiotics are defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. Primary prevention studies often employ a perinatal supplementation protocol in which pregnant women are supplemented with probiotics during the final weeks of pregnancy, followed by direct supplementation of the infant. Such studies enroll mothers at high risk for delivering an infant likely to develop atopic dermatitis, with the risk factor determined by family history.
To date, eight randomized controlled trials assessing nine different probiotics or probiotic combinations have been published on the primary prevention of eczema, and these trials have produced conflicting results. The large heterogeneity in results might be explained by several factors. First, it is apparent that different probiotic strains or combinations of probiotics would be expected to elicit different effects. This explanation is insufficient, however, based on the observation that studies on the same single strain of Lactobacillus rhamnosus GG (LGG) have reported dramatically different results.4,5 Next, differences in outcomes may be due, in part, to differences in doses or routes of administration. Finally, not all studies have confirmed the colonization of probiotic bacteria in the intestine and some studies have reported alterations in the microflora that were not reflective of the administered bacteria.
The Hygiene Hypothesis
The mechanisms of action by which probiotic supplementation might reduce allergic diseases have not been elucidated, but could be related to changes in the gut microbiota, immunological effects, or a combination of these.
Differences in the intestinal flora between allergic and non-allergic infants and children have been identified, which predicate the development of allergic disease, including eczema, suggesting a potential causal relationship.6,7 Specifically, bifidobacteria and lactobacilli are more often found in the microbiota of non-allergic children.6,8
The hygiene hypothesis provides a framework for understanding the increased incidence of allergic diseases in the context of microbial and immune interactions. According to the hygiene hypothesis, the increased prevalence of allergic diseases in children may be associated with reduced exposure to microbial components early in life.9 The hygiene hypothesis suggests, in part, that a lack of early microbial exposure is associated with an imbalance in the neonatal development of T helper (Th)1 and (Th)2 cells, contributing to the increased prevalence of Th2-associated allergic diseases. Indeed, children at high risk of developing allergic disease early in life are characterized by a Th2-polarized cytokine profile.10 As their name suggests, Th cells help to orchestrate the immune response by driving both cell-mediated responses and antibody responses, depending on the activating environment. Naïve Th0 cells can differentiate upon stimulation into either a Th1 or a Th2 cell lineage, which differ in the cytokines, or chemical signaling molecules, they produce.
Different cytokine profiles trigger different effects. In general, a Th1-dominant cytokine profile is characterized by interferon (IFN)-γ and is associated with the activation of cellular immunity. In contrast, a Th2 cytokine profile, characterized by IL-4, IL-5, and IL-13, is associated with humoral immunity, or antibody production.
The PandA Trial (Probiotics and Allergy)
Little is known about the strain-specific effects of probiotics on cytokine production in vivo, especially in human infants. However, the PandA trial, the most recent study published on the effectiveness of probiotics for the prevention of childhood eczema, included a detailed evaluation of immune modulation in infants.11 This study is unique in that probiotic strains were selected from an original pool of 69 strains in a multi-stage process. Candidate strains were selected based on stability and resistance to gastric acid, bile salts, and pancreatic enzymes,12 and then further selected according to in vitro cytokine production in adult human PBMCs and infant cord blood cells.13,14
In the end, Bifidobacterium bifidum W23, Bifidobacterium lactis W52, and Lactococcus lactis W58, were selected based on their capacity to induce the production of regulatory IL-10 and a reduction in the Th2 cytokines IL-5 and IL-13. Supplementation with combined B. bifidum, B. lactis, and Lc. lactis reduced the incidence of infant eczema at three months of age by 58 per cent.
Early colonization with Lc. lactis and Bifidobacterium spp. was confirmed by qPCR, and the production of IL-5 and IL-13 was lower in the probiotic-treated group whether or not those infants developed eczema. An ex vivo analysis, in which whole blood samples obtained from study infants at age three months were stimulated in culture, demonstrated a significant reduction in IL-5 and a trend towards decreased IL-13, and the authors proposed that the observed reduction in the incidence of eczema may have been related to altered immune signaling, specifically a decrease in Th2-mediated immunity.
Conclusion
The PandA trial is the first study of a combination probiotic intervention for the primary prevention of childhood eczema in which strains were selected based on in vitro cytokine production. This unique combination of three probiotic strains reduced the risk of infant eczema by 58 per cent at three months. A beneficial effect persisted through the age of two years, suggesting a lasting impact on immune balance.
References:
1. Hanifin JM, Reed ML. A population-based survey of eczema prevalence in the United States. Dermatitis. 2007;18(2):82-9.
2. Holgate ST, Lack G. Improving the management of atopic disease. Arch Dis Child. 2005;90(8):826-31.
3. Burgess JA, Dharmage SC, Byrnes GB,et al. Childhood eczema and asthma incidence and persistence: A cohort study from childhood to
middle age. J Allergy Clin Immunol. 2008;122(2):280-5.
4. 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.
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no clinical effects of Lactobacillus GG supplementation. Pediatrics. 2008;121(4):e850-6.
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7. Penders J, Thijs C, Van den Brandt PA, et al. Gut microflora composition and development of atopic manifestations in infancy: the KOALA
birth cohort study. Gut. 2007;56:661-7.
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and was not developing. J Allergy Clin Immunol. 2001;107:129-34.
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10. van der Velden V, Laan MP, Baert MR, de Waal MR, Neijens JH, Savelkoul HF. Selective development of a strong Th2 cytokine profile in highrisk
children who develop atopy: risk factors and regulatory role of IFN-gamma, IL-4 and IL-10. Clin Exp Allergy. 2001;31:997-1006.
11. Niers L, Martin R, Rijkers G, et al. The effects of selected probiotic strains on the development of eczema (the PandA study). Allergy. 2009:
epub ahead of print.
12. Timmerman HM, Niers LE, Ridwan BU, et al. Design of a multispecies probiotic mixture to prevent infectious complications in critically ill
patients. Clin Nutr. 2007;26:450-9.
13. Niers LE, Timmerman HM, Rijkers GT, et al. Identification of strong interleukin-10 inducing lactic acid bacteria which down-regulate T
helper type 2 cytokines. Clin Exp Allergy. 2005;35:1481-9.
14. Niers LEM, Hoekstra MO, Timmerman HM, et al. Selection of probiotic bacteria for prevention of allergic diseases: immunomodulation of
neonatal dendritic cells. Clin Exp Immunol. 2007;1-9.
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