Probiotics to Treat Childhood Eczema: Another Useful Lactobacillus Strain
Abstract & Commentary
By David Kiefer, MD. Dr. Kiefer is Clinical Instructor, Family Medicine, University of Washington, Seattle; Clinical Assistant Professor of Medicine, University of Arizona, Tucson; Adjunct Faculty, Bastyr University, Seattle; he reports no financial relationship to this field of study.
Synopsis: A newly identified probiotic strain, Lactobacillus sakei KCTC 10755BP, was found to improve symptoms of moderate-to-severe eczema in children 2-10 years old.
Source: Woo SI, et al. Effect of Lactobacillus sakei supplementation in children with atopic eczema-dermatitis syndrome. Ann Allergy Asthma Immunol 2010;104:343-348.
The researchers in this study recruited children ages 2-10 years with atopic eczema dermatitis syndrome (hereafter called "eczema") from a hospital pediatrics department. The children needed to have an eczema rating (using the SCORAD rating system, SCORing for Atopic Dermatitis) that put them in the moderate (SCORAD 25-50) or severe (SCORAD > 50) category, and could not have used cyclosporine, systemic corticosteroids, topical calcineurin inhibitors, or Chinese medicines in the last 3 months.
Eighty-eight children were randomized, in a double-blind fashion, to receive either 5 billion colony forming units (CFU) twice daily of Lactobacillus sakei (n = 45) or placebo (n = 43), and followed for 12 weeks. Patients were allowed to use emollients after bathing and topical corticosteroids (amount used was measured) as needed. Three aspects of the SCORAD rating system (total, extent and intensity, and itch and sleep loss) were used at time -2 weeks, 0, 6, and 12 weeks, to assess the status of the subjects' eczema. Laboratory tests were also followed, for total IgE, IgE to local common allergens, eosinophil cationic protein, and various chemokines related to immune system and allergy activity. Specifically, the researchers measured the levels of thymus and activation-regulated chemokine (CCL17) and cutaneous T-cell-attracting chemokine (CCL27), both of which have been shown to be correlated with eczema severity.
After 3 months, 41 children in the probiotic group had finished the trial, compared to 34 in the placebo group, which the authors said was not significant (P = 0.11); relevant to the dropouts, the authors did not mention that an intention-to-treat analysis was used in the final analysis. Over the 12 weeks, both the probiotic and placebo groups had improved total SCORAD scores when compared to baseline (P > 0.001 and P = 0.007, respectively). Comparing the probiotic and placebo groups' total SCORAD score, there was no difference at week 6, but at week 12 the probiotic group had a statistically significantly lower total SCORAD than the placebo group (P = 0.01), with an average decrease of 13.1 compared to 5.2, respectively (P = 0.008, for this change in SCORAD values). Another way to look at the clinical situation at the end of the study is to compare the number of subjects who achieved at least 30% or 50% improvement in their total SCORAD. The probiotic group was significantly better than the placebo group for both 30% (P = 0.002) and 50% (P = 0.04).
The laboratory analyses showed a correlation, as expected, between SCORAD values and the chemokines, CCL17 and CCL27. The levels of these chemokines from baseline decreased over the study period in both the probiotic (P < 0.001) and the placebo (P = 0.20-0.70) groups, but only the decrease in the probiotic group achieved significance. There was no difference in the number of patients using topical corticosteroids or the amount of corticosteroid used in the probiotic vs. the placebo groups over the duration of the trial.
Commentary
The idea that probiotic supplementation either in utero, for the breastfeeding mother, or for newborns, can help prevent atopy is not new; data from numerous RCTs and reviews are most convincing for a decreased incidence of atopy, especially in children from families with numerous atopic individuals.1-4 Of note, some research trials have not shown a benefit with probiotic supplementation, and the data are less convincing for the treatment of eczema. In addition, the focus of research has been on children less than 1 year of age, a crucial time when colonization of the gastrointestinal tract occurs and, presumably, can be manipulated favorably with probiotic supplementation. In this context, the trial being reviewed here is interesting because is adds to a smaller, though intriguing, research base focusing on older children, and investigates treatment rather than prevention of eczema.
In this study, 5 billion CFU of Lactobacillus sakei twice daily over 12 weeks improved symptoms of eczema in children ages 2-10 years. It is interesting that the placebo group also improved over the 12 weeks, not a surprise given that emollients and topical steroids were allowed. However, the amount of steroids used was similar between the two groups, and the probiotic group improved more than the placebo group; the probiotic effect seems to be "real" and clinically significant. In the context of other research, the dose is higher than that used in prior studies (more common pediatric dose is 5 billion CFU daily), avoiding one criticism that results of negative trials were due to underdosing.
What is the mechanism of the effects observed in this trial? This particular strain may have improved eczema through inhibitory effects on Staphylococcus aureus (very preliminary research), or modulation of immune system effects, as demonstrated from prior basic science research and changes in some relevant chemokines like CCL17 and CCL27. The authors do not address a gastrointestinal mechanism, the idea that probiotics, by providing beneficial bacteria to the colon and distal small bowel, affect cellular and intercellular function and structure, possibly the ultimate reason why immune system changes and decreased allergic responses are observed. Although it is more difficult to test intestinal permeability or colonic bacteria contents, these would have been very interesting additions to the research presented here.
What remains "at large" is the issue of which strains and doses are best for which clinical conditions. Should we prescribe a mixture or just one species for a given diagnosis? The data from the medical literature are probably in their infancy (no pun intended) about this topic; there is clearly the need for more trials like the one reviewed here to define the exact effects of specific strains, and the effective dose that affects a particular clinical condition.5 Some of the research has been sponsored by manufacturers with patented strains and these companies' vested interest in showing beneficial effects of "their" bacteria can make interpretation of the research results more difficult. That said, in some cases, their research budgets have led to interesting clinical results that are hard to ignore. However, are these positive strains the only effective ones, or does it just represent and reflect companies with adequate resources to do the testing? In this context, it is good to see that this relatively well-done research trial used government funding (National Research Foundation of Korea).
In summary, this is an interesting result for a relatively underinvestigated topic, the use of probiotics to treat atopic dermatitis and eczema in older children. At least preliminarily, we can add this species of bacteria and its effective dose to mounting evidence of the efficacy of probiotics for atopy. We can hope that future studies will clarify these findings and test this species in combination or head-to-head with other probiotic bacteria to definitively provide clinicians with a diagnosis-species-dose guidebook.
References
1. Kligler B, Cohrssen A. Probiotics. Am Fam Physician 2008;79:1073-1078.
2. Hsieh MH, Versalovic J. The human microbiome and probiotics: Implications for pediatrics. Curr Probl Pediatr Adolesc Health Care 2008;38:309-312.
3. Kalliomaki M, et al. Probiotics and prevention of atopic disease: 4-year follow-up of a randomised placebo-controlled trial. Lancet 2003;361:1869-1871.
4. Kalliomaki, M, et al. 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;119:1019-1021.
5. Boyle RJ, et al. Probiotics for treating eczema. Cochrane Database Syst Rev 2008,(4):CD006135; doi: 10.1002/14651858.CD006135.pub2 .
A newly identified probiotic strain, Lactobacillus sakei KCTC 10755BP, was found to improve symptoms of moderate-to-severe eczema in children 2-10 years old.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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