Lactobacillus plantarum-derived Extracellular Vesicles Protect Atopic Dermatitis Induced byStaphylococcus aureus-derived Extracellular Vesicles

Abstract

PurposeThe 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 compositionMethodsTwenty-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.ResultsThe 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.ConclusionsWe 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.

Bacterial extracellular vesicles: A new way to decipher host‐microbiota communications in inflammatory dermatoses

“…For example, based on metagenomic analysis, a protective role of lactic acid‐producing bacteria, such as Lactobacillus plantarum , was previously suggested in atopic dermatitis . In this study, L. plantarum ‐derived EVs were able to protect mice from atopic dermatitis induced by S. aureus ‐derived EVs . It suggests that L. plantarum ‐derived EVs could help preventing skin inflammation in atopic dermatitis context.…”

“…In parallel, interesting clinical applications resulting from EV discovery could be based on the crosstalk existing between EVs from different microorganisms belonging to human microbiota. For example, based on metagenomic analysis, a protective role of lactic acid‐producing bacteria, such as Lactobacillus plantarum , was previously suggested in atopic dermatitis . In this study, L. plantarum ‐derived EVs were able to protect mice from atopic dermatitis induced by S. aureus ‐derived EVs .…”

“…Nowadays, according to the International Society for Extracellular Vesicles (ISEV), the term “Extracellular Vesicle” is the generic term for particles delimited by a lipid bilayer that cannot replicate and commonly released from a cell . Bacterial EVs are natural messengers, implicated in intra‐ and interspecies cell‐to‐cell communication among microorganism populations present in microbiota . In this first part, we describe the different production routes, their immunomodulatory potential, antibioresistance and virulence factors (Figure ).…”

“…In future years, when metaproteomic and metatranscriptomic analysis will be possible in large scale and in parallel, high‐throughput analysers will be precise enough to detect these small molecules in small amounts, specific EV signatures associated with inflammatory diseases may be profiled, in prediction and/or prognosis of treatment response and disease severity. This kind of approach was previously suggested for cancer metastasis sites in eukaryotic cells, and may be shortly considered in skin inflammatory diseases, especially those where dysbiosis was identified as a key player: acne, atopic dermatitis, psoriasis and hidradenitis suppurativa …”

Preparation and Characterization of a Polar Milk Lipid-enriched Component from Whey Powder

“…The effect of EVs from L. plantarum in the prevention or inhibition of inflammation has already been reported in many studies (Kim et al, 2018;Molina-Tijeras et al, 2019).…”