Probiotics may improve pediatric AD symptoms

A daily capsule of a cocktail of probiotics may reduce both the severity symptoms in moderate atopic dermatitis and the need for topical corticosteroids to treat symptom flare ups in children, research published in JAMA Dermatology suggests.¹

In recent years, research has demonstrated close links between gut microflora and many factors involved in the pathogenesis of atopic dermatitis, such as immunity. Patients with atopic dermatitis have been shown to have different faecal microbiota compared to healthy control subjects,² and the composition and diversity of the gut microbiota of young children who later developed atopic dermatitis have been shown to be different from those of children who did not.³

Up to 20% of children are affected by atopic dermatitis and a group of researchers based in Spain decided to test whether there was a potential role for probiotics in their treatment.

Dr. VicenteLead author Vicente Navarro-López, M.D., Ph.D., of the Universidad Católica San Antonio de Murcia (UCAM) in Spain, said: “Several studies have already explored the efficacy of certain probiotics in the prevention and treatment of atopic dermatitis. Overall, the current evidence suggests that probiotics could be an option to improve moderate and severe atopic dermatitis recovery rates in children and adults; however, to date, there is no strong experimental evidence supporting their effectiveness and safety in clinical practice.

Importantly, evidence and clinical trials demonstrating strain-specific effects are lacking.”

The study

The group conducted a double-blind, placebo-controlled trial, between March and June 2016, at a hospital in Alicante, Spain. The study involved 50 children, aged 4 to 17 years with moderate atopic dermatitis, who were randomized according to sex, age, and age of onset of atopic dermatitis to a daily capsule containing freeze-dried powder with 109 total colony-forming units of the probiotic strains Bifidobacterium lactis CECT 8145, B longum CECT 7347, and Lactobacillus casei CECT 9104 and maltodextrin as a carrier, or maltodextrin-only capsules (placebo) for 12 weeks. None of the children involved had received systemic immunosuppressive drugs in the previous three months or antibiotics in the previous two weeks, and none had a diagnosed intestinal bowel disease or signs of bacterial infection.

After 12 weeks children who had taken probiotics saw a 19.2 points greater reduction in the SCORAD (Scoring Atopic Dermatitis) index than those who took the placebo capsule (mean difference, −19.2; 95%CI, −15.0 to −23.4). In relative terms, the SCORAD index fell by 83% in the probiotic group (95%CI, −95% to −70%) compared to 24% (95%CI, −36%to −11%) in the placebo group (P < .001).

Two of the subcomponents of the SCORAD index (eczema spread and intensity) showed clear improvement in the children who took probiotics compared with those who took placebo, but there was no statistically significant difference in the third subcomponent - subjective symptoms. In the probiotic group subjective symptoms fell by 77%, but they also fell substantially in the placebo group – by 53%.

Dr. Navarro-López suggests that this might be because patients who took placebo might have been able to reduce symptoms such as pruritus by using more corticosteroids.

The usual treatment for mild-to-moderate atopic dermatitis is a course of topical corticosteroids, and long term topical steroids for moderate to severe disease.

Children who took probiotics in the study used topical steroids to treat atopic dermatitis flare ups on significantly fewer days (161 of 2084 patient-days [7.7%]) than those who took the placebo capsule (220 of 2032 patient-days [10.8%]; odds ratio, 0.63; 95%CI, 0.51 to 0.78).

Dr. Navarro-López said: “Our results suggest that administration of this mixture of probiotics, as adjuvant treatment, may be effective in reducing the SCORAD index and, subsequently, decreasing the use of steroids during atopic dermatitis flares.”

He added that the clinical response documented in the probiotic group was greater than that obtained with other probiotics tested previously and suggested that a greater effect may have been seen due to the longer length of treatment and the patients involved in this particular trial.

“Treatment longer than eight weeks might condition the positive effect of probiotic use, patients older than 1 year have a greater response to probiotics, patients with moderate to severe atopic dermatitis have a better response, and a mixture of probiotics has better beneficial effects than a single probiotic, especially when lactobacilli and bifidobacteria are included in the mixture,” he said.

“The final blend used in the study was selected on the basis of published results and internal unpublished data,” he added.

The physiology of gut microbiota in atopic derm

So how might gut microbiota be implicated in atopic dermatitis and probiotics exert their effects?

It has been suggested that there is an association between a disruption in intestinal barrier function and the origin of atopic dermatitis, mediated by immunological activation leading to a type 2 dominant inflammation, which would suggest that gut microbiota could play an important immunomodulatory role in the development of normal immune tolerance. A predominance of T helper two cells rather than T helper 1, causes an imbalance that might aggravate the pathogenesis of atopic dermatitis, increasing IgE and activating interleukins.

Low levels of Faecalibacterium prausnitzii and an associated reduction in short chain fatty acid production have been implicated in Crohn’s disease, and a recent analysis of the gut microbiota of patients with atopic dermatitis has shown an intraspecies compositional change in Faecalibacterium prausnitzii that reduces the number of high butyrate and propionate producers.

Butyrate and propionate are microbial-produced short-chain fatty acids with an anti-inflammatory role, and butyrate has been shown to be a key player in maintaining gut barrier integrity. Therefore, reduced levels in the microbiota of both butyrate and propionate producers may result in a pro-inflammatory state in the gut and a loss of barrier integrity.

This raises a potential role for probiotics as microbiota recovery players in atopic dermatitis, Dr Navarro-López said.

Disclosures: The study was sponsored by Biopolis with participation by Archer Daniels Midland in the U.S. and Korott in Spain.

References

1. Navarro-López V, Ramírez-Boscá A, Ramón-Vidal D, Ruzafa-Costas B, Genovés-Martínez S, Chenoll-Cuadros E, Carrión-Gutiérrez M, Horga de la Parte J, Prieto-Merino D, Codoñer-Cortés FM. Effect of Oral Administration of a Mixture of Probiotic Strains on SCORAD Index and Use of Topical Steroids in Young Patients With Moderate Atopic Dermatitis: A Randomized Clinical Trial. JAMA Dermatol. 2017 Nov 8. doi: 10.1001/jamadermatol.2017.3647.

2. Watanabe S. & Nansawa Y. (2003) Differences in fecal microflora between patients with atopic dermatitis and healthy control subjects. Journal of Allergy and Clinical Immunology 111, 587–591.

3. Wang M., Karisson C., Olsson C., Adlerberth I., Wold A., Strachan D.P., et al. (2008) Reduced diversity in the early fecal microbiota of infants with atopic eczema. Journal of Allergy and Clinical Immunology 121, 129–134.

4. Song H, Yoo Y, Hwang J, Na YC, Kim HS. Faecalibacterium prausnitzii subspecies-level dysbiosis in the human gut microbiome underlying atopic dermatitis. J Allergy Clin Immunol. 2016;137(3):852-860.