Allergy Asthma Immunol Res.  2018 Sep;10(5):516-532. 10.4168/aair.2018.10.5.516.

Lactobacillus plantarum-derived Extracellular Vesicles Protect Atopic Dermatitis Induced by Staphylococcus aureus-derived Extracellular Vesicles

Affiliations
  • 1Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea. mineyang81@ewha.ac.kr
  • 2Research Institute, AEON Medix, Inc., Pohang, Korea.
  • 3Department of Life Science, Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Korea.
  • 4Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea.
  • 5Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
  • 6Institute of MD Healthcare, Inc., Seoul, Korea.
  • 7CJ R&D Center, CJ CheilJedang Corporation, Suwon, Korea.
  • 8Pediatric Allergy and Respiratory Center, Department of Pediatrics, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Korea. bypyun@schmc.ac.kr
  • 9Department of Computer Science and Engineering, Hanyang University, Seoul, Korea.
  • 10Department of Internal Medicine, National Medical Center, Seoul, Korea.

Abstract

PURPOSE
The microbial environment is an important factor that contributes to the pathogenesis of atopic dermatitis (AD). Recently, it was revealed that not only bacteria itself but also extracellular vesicles (EVs) secreted from bacteria affect the allergic inflammation process. However, almost all research carried out so far was related to local microorganisms, not the systemic microbial distribution. We aimed to compare the bacterial EV composition between AD patients and healthy subjects and to experimentally find out the beneficial effect of some bacterial EV composition
METHODS
Twenty-seven AD patients and 6 healthy control subjects were enrolled. After urine and serum were obtained, EVs were prepared from samples. Metagenomic analysis of 16s ribosomal DNA extracted from the EVs was performed, and bacteria showing the greatest difference between controls and patients were identified. In vitro and in vivo therapeutic effects of significant bacterial EV were evaluated with keratinocytes and with Staphylococcus aureus-induced mouse AD models, respectively.
RESULTS
The proportions of Lactococcus, Leuconostoc and Lactobacillus EVs were significantly higher and those of Alicyclobacillus and Propionibacterium were lower in the control group than in the AD patient group. Therefore, lactic acid bacteria were considered to be important ones that contribute to the difference between the patient and control groups. In vitro, interleukin (IL)-6 from keratinocytes and macrophages decreased and cell viability was restored with Lactobacillus plantarum-derived EV treatment prior to S. aureus EV treatment. In S. aureus-induced mouse AD models, L. plantarum-derived EV administration reduced epidermal thickening and the IL-4 level.
CONCLUSIONS
We suggested the protective role of lactic acid bacteria in AD based on metagenomic analysis. Experimental findings further suggest that L. plantarum-derived EV could help prevent skin inflammation.

Keyword

Atopic dermatitis; Lactobacillus; microbiome; metagenomics; probiotics

MeSH Terms

Alicyclobacillus
Animals
Bacteria
Cell Survival
Dermatitis, Atopic*
DNA, Ribosomal
Extracellular Vesicles*
Healthy Volunteers
Humans
In Vitro Techniques
Inflammation
Interleukin-4
Interleukins
Keratinocytes
Lactic Acid
Lactobacillus*
Lactococcus
Leuconostoc
Macrophages
Metagenomics
Mice
Microbiota
Probiotics
Propionibacterium
Skin
Staphylococcus*
Therapeutic Uses
DNA, Ribosomal
Interleukin-4
Interleukins
Lactic Acid
Therapeutic Uses
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