Ruminococcus gnavus ameliorates atopic dermatitis by enhancing Treg cell and metabolites in BALB/c mice.

BACKGROUND: Ruminococcus gnavus (R. gnavus) are mucin-degrading gut bacteria that play a key role in the early colonization of the gut by serving as endogenous sources of nutrients. They can also influence immune development. We had previously reported a lower abundance of R. gnavus in infants with atopic dermatitis (AD) compared with that in healthy subjects. However, the underlying mechanisms remain unclear. In this study, we investigated the effect of orally administered R. gnavus on antibiotic treatment-induced gut dysbiosis (and the underlying mechanism) in a mouse model of AD. METHODS: Four-week-old female BALB/C mice were administered antibiotic cocktails for 2 weeks. R. gnavus was orally administered throughout the study duration. At 6 weeks of age, AD was induced by epidermal sensitization with ovalbumin. AD phenotypes and systemic and gut immune responses were investigated. RESULTS: Orally administered R. gnavus significantly reduced AD-associated parameters (i.e., transepidermal water loss, clinical score, total serum immunoglobulin (Ig) E level, OVA-specific IgE level, and skin inflammation). R. gnavus treatment also resulted in significant downregulation of T helper 2-related cytokine mRNA and upregulation of interleukin (IL)-10 and Foxp3 in the skin. The population of CD4+ FOXP3+ T cells in mesenteric- and skin-draining lymph nodes and butyrate levels in the cecum increased in R. gnavus-administered AD mice. CONCLUSIONS: Immune modulation by orally administered R. gnavus may alleviate AD symptoms through the enhancement of regulatory T-cell counts and short-chain fatty acids production in AD mice.

Exposure to Polyhexamethylene Guanidine Exacerbates Bronchial Hyperresponsiveness and Lung Inflammation in a Mouse Model of Ovalbumin-Induced Asthma.

Humidifier disinfectants (HDs) exposure has now been associated with acute lung injury and pulmonary fibrosis; polyhexamethylene guanidine (PHMG) has been confirmed to cause severe lung inflammation and fibrosis in mice. Recent evidence also indicates that HDs exposure increases the asthma risk in children, but the underlying mechanisms remain unclear. We aimed to investigate the effects of PHMG exposure on asthma in mice and the potential underlying mechanisms. BALB/c mice were intranasally administered PHMG (0.1 mg/kg/day; 5 days per week) during 2 episodes of ovalbumin (OVA) sensitization and were then challenged with 1% OVA by inhalation. Bronchial hyperresponsiveness (BHR), inflammatory cell influx into bronchoalveolar lavage (BAL) fluid, serum total and OVA-specific immunoglobulin (Ig) E levels, and histopathological changes in the lung were analyzed. The levels of asthma-related cytokines and chemokines were assayed in the lung tissues to evaluate possible mechanisms. Exposure to PHMG following OVA sensitization and challenge significantly enhanced BHR, inflammatory cell counts in BAL fluid, airway inflammation, and total serum IgE levels in the asthma mouse model. In addition, the levels of chemokine ligand (CCL) 11 and serpine F1/pigment epithelium-derived factor (SERPINF1) were significantly elevated in the lungs of these mice compared to those in the control and OVA-treated only groups. Our findings suggest that PHMG can enhance the development of allergic responses and lung inflammation via CCL11- and SERPINF1-induced signaling in a mouse model of asthma.

Effects of chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) on Th2/Th17-related immune modulation in an atopic dermatitis mouse model.

Exposure to chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) has been associated with allergic contact dermatitis and occupational asthma. Despite this association however, no study has investigated the effects of CMIT/MIT exposure on the development of atopic dermatitis (AD). This study was conducted to investigate the influence of epicutaneous exposure to CMIT/MIT on AD in a mouse model and the underlying biological mechanisms. BALB/C mice were exposed to CMIT/MIT for 3 weeks and AD was developed using ovalbumin (OVA) epidermal sensitization. CMIT/MIT epicutaneous exposure in normal mice significantly enhanced AD-like phenotypes (e.g., transepidermal water loss, clinical score, total serum immunoglobulin E level and infiltration of inflammatory cells). In addition, CMIT/MIT exposure significantly augmented the mRNA expression level of T helper (Th) 2-related cytokines (thymic stromal lymphopoietin, interleukin (IL)-6 and IL-13), Th2 chemokine (chemokine (C-C motif) ligand 17) and the population of CD4+IL-4+ cells in the skin. Moreover, mice exposed to CMIT/MIT in the OVA challenge had greater AD-like phenotypes, higher IL-4 and IL-17A skin mRNA expression levels, and a larger population of CD4+IL-4+- and IL-17A+-producing cells in the skin-draining lymph nodes. Our current findings in a mouse model thus suggest that CMIT/MIT exposure may cause AD symptoms through the dysregulation of Th2/Th17-related immune responses.

Effects of kestose on gut mucosal immunity in an atopic dermatitis mouse model.

BACKGROUND: Atopic dermatitis (AD) is recently increasing among populations, but the underlying mechanisms remain controversial. Interactions between the gut microbiota and mucosal immunity are considered to be a crucial etiology. Fructooligosaccharide (FOS), prebiotics have been reported as activators of the gut microbiota. OBJECTIVE: The aim of this study was to investigate the effects of kestose, the smallest FOS and FOS on atopic dermatitis in mice. METHODS: An AD mouse model was developed by (ovalbumin) epidermal sensitization using BALB/c mice. Kestose (1%, 5%, and 10%) or FOS (5%, positive control) was orally administered throughout the study. RESULTS: In comparison with the values observed for the control AD mice, transepidermal water loss (TEWL), clinical score, and skin inflammation on histopathology were significantly decreased by the oral administration of kestose. Total IgE, thymic stromal lymphopoietin (TSLP) in skin, and IL-4 were also suppressed by this administration. In addition, the population of CD4+Foxp3+ cells in mesenteric lymph nodes (MLNs) and acetate concentrations in feces were significantly increased by kestose treatment. CONCLUSIONS: These findings suggest that kestose activates the gut immune system to induce the tolerance against allergic skin inflammations in AD.