Abstract
Gut microbiota play an important role in immune responses and energy metabolism. In this study, we evaluated whether administration of Lactobacillus fermentum (L. fermentum) KBL375 isolated from healthy Korean feces improves the atopic dermatitis using the house dust mite (Dermatophagoides farinae)-induced atopic dermatitis (AD) mouse model. Administration of L. fermentum KBL375 significantly decreased dermatitis score, ear and dorsal thickness, and serum immunoglobulin E level in AD-induced mice. Significant reductions in mast cells and eosinophils were discovered in skin tissues from L. fermentum KBL375-treated mice. T helper 2 cell-related cytokines interleukin (IL)-4, IL-5, IL-13, and IL-31 significantly decreased, and anti-inflammatory cytokine IL-10 or transforming growth factor-β increased in skin tissues from L. fermentum KBL375-treated mice. In addition to phenotypic changes in skin tissues, L. fermentum KBL375 treatment induced an increase in the CD4+CD25+Foxp3+ cell population in mesenteric lymph nodes. Taxonomic and functional analyses of gut microbiota showed significantly higher cecum bacterial diversities and abundances including genus Bilophila, Dorea, and Dehalobacterium in L. fermentum KBL375-treated mice. Metabolic analysis of the cecum also showed significant changes in the levels of various amino acids including methionine, phenylalanine, serine, and tyrosine, as well as short chain fatty acids such as acetate, butyrate, and propionate in AD-induced mice due to L. fermentum KBL375 treatment. These altered metabolites in AD-induced mice returned to the levels similar to those in control mice when treated with L. fermentum KBL375. Therefore, L. fermentum KBL375 could be useful for AD treatment by modulating the immune system and inducing various metabolites.
Highlights
Atopic dermatitis (AD) is characterized by chronic and abnormal inflammation of the skin with compromised skin barrier integrity, high inflammatory responses toward stimulants, and a reduction in antimicrobial responses (Rather et al, 2016)
Skin samples from atopic dermatitis (AD)-induced mice treated with L. fermentum KBL375 showed significant reductions in mRNA levels of thymic stromal lymphopoietin (TSLP), macrophage-derived chemokine (MDC), or thymus and activation regulated chemokine (TARC) compared to controls
This study clearly demonstrated that the L. fermentum KBL375 treatment showed various protective effects against AD, such as improvements of clinical symptoms, immunomodulation of the host, and changes in metabolic pathways due to gut microbiota restoration
Summary
Atopic dermatitis (AD) is characterized by chronic and abnormal inflammation of the skin with compromised skin barrier integrity, high inflammatory responses toward stimulants, and a reduction in antimicrobial responses (Rather et al, 2016). During the acute phase of AD, an increase in T helper (Th) 2 cells occurs in skin lesions (Meagher et al, 2002; Peng and Novak, 2015). The concentrations of Th2-related chemokines, including macrophage-derived chemokine (MDC) and thymus and activation regulated chemokine (TARC), associated with the infiltration of inflammatory cells into skin lesions, show a strong correlation with the severity of AD (Nakazato et al, 2008; Kim et al, 2013). Th1 and Th17 cells gradually increase during the chronic development of AD (Meagher et al, 2002; Peng and Novak, 2015), and Foxp3+ T regulatory cell (Treg) populations can inhibit AD development via production of anti-inflammatory cytokine IL-10 and transforming growth factor (TGF)-β (Zhang et al, 2014)
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