Hope Allen

Introduction. Atopic Dermatitis (AD) is a chronic inflammatory skin disease with causal links ranging from a dysregulated immune response, genetic factors, and the environment.¹ AD is diagnosed by the presence of itching, epidermal barrier dysfunction, lesions with increased T-helper 2 (Th2) cells, mast cells, eosinophils, and increased IgE levels.² AD affects 20% of children and 3% of adults worldwide, usually presenting between the ages of 3-7.³ It is the most common form of eczema, with a two to three-fold higher prevalence seen in industrialized nations.³ Studies have found that a large number of AD patients have decreased diversity in their gut microbiomes, including decreased Bifidobacterium and Bacteroides populations, leading to decreased short chain fatty acid (SCFA) production.⁴ Additional studies have found that decreased bacterial populations and SCFA synthesis can lead to a decrease in the number of regulatory T cells (Tregs), and an increase in Th2 cells, eosinophils, and IgE levels leading to systemic inflammation, which plays a role in modulating Atopic Dermatitis.^2,5,6 These findings suggest a potential link between the gut microbiome and Atopic Dermatitis, and potential treatments for this disease. Methods. In vitro and in vivo experiments were conducted. Bone marrow dendritic cells (BMDCs) and naïve CD4 T- cells were cultured with a probiotic mixture called Duolac ATP which contained four different strains of Lactobacillus and Bifidobacterium.⁶ Cultures were examined for the presence of anti-inflammatory cytokines and the presence of FoxP3 Treg cells using flow cytometry.⁶ In vivo, mice were induced to have AD and treated with Duolac ATP. After 28 days, ear samples were examined for epithelial thickness, and serum samples were examined to determine IgE levels.⁶ Blood cultures were collected, and western blot was performed to observe the presence of Th1 and Th2 promoting transcription factors.⁶ Results. Duolac ATP treated BMDC cultures showed increased levels of anti-inflammatory cytokines IL-10 and TGF-beta.⁶ Duolac ATP treated CD4 T-cells showed increased levels of FoxP3 Tregs.⁶ AD mice treated with Duolac ATP displayed decreased ear thickness, decreased IgE levels in serum, and decreased visible AD skin lesions and symptoms.⁶ Probiotic treated mice also showed better T-cell balance by increasing Th1 transcription factors and decreasing Th2 transcription factors.⁶ Conclusions. Studies have found that AD mice have dysregulated immune responses, which can be altered through the application of probiotic mixtures leading to increased anti-inflammatory cytokines, Tregs, and decreased IgE levels, thus providing a novel therapeutic and clinical intervention strategy.^4-6

1.  Lee, S., Lee, E., Park, Y. and Hong, S. Microbiome in the Gut-Skin Axis in Atopic Dermatitis. Allergy, Asthma & Immunology Research. 2018; 10(4), p.354. doi: 4168/aair.2018.10.4.354
2. Kim HW, Ju DB, Kye Y-C, et al. Galectin-9 Induced by Dietary Probiotic Mixture Regulates Immune Balance to Reduce Atopic Dermatitis Symptoms in Mice. Frontiers in Immunology. 2020;10. doi:10.3389/fimmu.2019.03063
3. Nakatsuji, T., Gallo, R. The role of the skin microbiome in atopic dermatitis. Annals of Allergy, Asthma & Immunology. 2019; 122(3), doi: https://doi.org/10.1016/j.anai.2018.12.003
4. Kim, J. and Kim, H. Microbiome of the Skin and Gut in Atopic Dermatitis (AD): Understanding the Pathophysiology and Finding Novel Management Strategies. Journal of Clinical Medicine. 2019; 8(4), p.444. doi: 10.3390/jcm8040444
5. Bhaskaran N, Quigley C, Paw C, Butala S, Schneider E, Pandiyan P. Role of Short Chain Fatty Acids in Controlling Tregs and Immunopathology During Mucosal Infection. Frontiers in Microbiology. 2018;9. doi:10.3389/fmicb.2018.01995
6. Kim, H., Hong, R., Choi, E., Yu, K., Kim, N., Hyeon, J., Cho, K., Choi, I. and Yun, C. A Probiotic Mixture Regulates T Cell Balance and Reduces Atopic Dermatitis Symptoms in Mice. Frontiers in Microbiology. 2018; 9. doi: 10.3389/fmicb.2018.02414