Asthma, obesity, and microbiota: A complex immunological interaction.

Obesity and allergic asthma are inflammatory chronic diseases mediated by distinct immunological features, obesity presents a Th1/Th17 profile, asthma is commonly associated with Th2 response. However, when combined, they result in more severe asthma symptoms, greater frequency of exacerbation episodes, and lower therapy responsiveness. These features lead to decreased life quality, associated with higher morbidity/mortality rates.  In addition, obesity prompts specific asthma phenotypes, which can be dependent on atopic status, age, and gender. In adults, obesity is associated with neutrophilic/Th17 profile, while in children, the outcome is diverse, in some cases children with obesity present aggravation of atopy, and Th2 inflammation, and in others an association with a Th1 profile, with reduced IgE levels and eosinophilia. These alterations occur due to a complex group of factors among which the microbiome has been recently explored. Particularly, evidence shows its important role in susceptibility or resistance to asthma development, via gut-lung-axis, and demonstrates its relevance to the immune pathogenesis of the syndrome. Few studies address the relevance of the lung microbiome in shaping the immune response, locally. However, specific bacteria, like Moraxella catarrhalis, Haemophilus influenza, and Streptococcus pneumoniae, correlate with important features of the obese-asthmatic phenotype. Although maternal obesity is known to increase asthma risk in offspring, the impact on lung colonization is unknown. This review details the main key immune mechanisms involved in obesity-aggravated asthma, featuring the effect of maternal obesity in the establishment of gut and lung microbiota of the offspring, acting as potential childhood asthma inducer.

Obesity affects peripheral lymphoid organs immune response in murine asthma model.

Asthma and obesity present rising incidence, and their concomitance is a reason for concern, as obese individuals are usually resistant to conventional asthma treatments and have more exacerbation episodes. Obesity affects several features in the lungs during asthma onset, shifting the T helper type 2 (Th2)/eosinophilic response towards a Th17/neutrophilic profile. Moreover, those individuals can present reduced atopy and delayed cytokine production. However, the impact of obesity on follicular helper T (Tfh) cells and B cells that could potentially result in antibody production disturbances are still unclear. Therefore, we aimed to assess the peripheral response to ovalbumin (OVA) in a concomitant model of obesity and asthma. Pulmonary allergy was induced, in both lean and obese female BALB/c mice, through OVA sensitizations and challenges. Mediastinal lymph nodes (MLNs) and spleen were processed for immunophenotyping. Lung was used for standard allergy analysis. Obese-allergic mice produced less anti-OVA IgE and more IgG2a than lean-allergic mice. Dendritic cells (CD11c+  MHCIIhigh ) expressed less CD86 and more PDL1 in obese-allergic mice compared with lean-allergic mice, in the MLNs. Meanwhile, B cells (CD19+  CD40+ ) were more frequent and the amount of PDL1/PD1+ cells was diminished by obesity, with the opposite effects in the spleen. Tfh cells (CD3+  CD4+  CXCR5+  PD1+ ) expressing FoxP3 were more frequent in obese mice, associated with the predominance of Th (CD3+  CD4+ ) cells expressing interleukin-4/GATA3 in the MLNs and interleukin-17A/RORγT in the spleen. Those modifications to the main components of the germinal centers could be resulting in the increased IgG2a production, which - associated with the Th17/neutrophilic profile - contributes to asthma worsening and represents an important target for future treatment strategies.

Ferulic acid supresses Th2 immune response and prevents remodeling in ovalbumin-induced pulmonary allergy associated with inhibition of epithelial-derived cytokines.

Asthma is characterized by intermittent airway obstruction and chronic inflammation, orchestrated primarily by Th2 cytokines. There is a strong rationale for developing new asthma therapies, since current treatment protocols present side effects and may not be effective in cases of difficult-to-control asthma. The purpose of this study was to evaluate the effect of ferulic acid, a phenolic acid commonly present in plants, in the ovalbumin-induced pulmonary allergy murine model. METHODS: BALB/c mice were sensitized and challenged with ovalbumin, and treatments were provided by gavage. Six groups of mice (n = 6) were studied, labeled as: control, pulmonary allergy, dexamethasone, and 3 receiving ferulic acid (at 25, 50, and 100 mg/kg). Lung tissue, bronchoalveolar lavage fluid and serum were collected for analysis. RESULTS: Ferulic acid treatment inhibited an established allergic Th2-response by decreasing the key features of pulmonary allergy, including lung and airway inflammation, eosinophil infiltration, mucus production and serum levels of OVA-specific IgE. These results were associated with lower levels of CCL20, CCL11 and CCL5 chemokines and IL-4, IL-5, IL-13, TSLP, IL-25 and IL-33 cytokines in lung tissue homogenate. CONCLUSIONS: In this study it was demonstrated for the first time that ferulic acid treatment is able to suppress one of the main features of the airway remodeling, indicated by reduction of mucus production, besides the Th2 pathogenic response on ovalbumin-induced pulmonary allergy. Taken together, results shows that the immunopathological mechanism underlying these effects is linked to a reduction of the epithelial-derived chemokines and cytokines, suggesting that ferulic acid may be useful as a potential therapeutic agent for asthma.

Influence of the leptin and cortisol levels on craving and smoking cessation.

Leptin inhibits cortisol release and may increase the craving for cigarettes, hindering the process of smoking cessation. We evaluate the influence of the initial concentration of cortisol and serum leptin on craving and smoking status in individuals after one month of treatment for smoking cessation. The leptin concentration was adjusted by the Initial Body Mass Index (BMI) (leptin/BMI) and the initial percentage of body fat (%BF) (leptin/%BF). The craving was assessed using the Questionnaire of Smoking Urges-Brief (QSU-Brief). The QSU-Brief was assessed about a score of factor 1 (positive reinforcement by tobacco), and factor 2 (negative reinforcement by tobacco). Correlation was found between QSU-Brief (Factor 1 and 2) with the initial concentration of leptin/BF% among those who continued to smoke. There was a negative correlation between cortisol levels and leptin/%BF in individuals who remained smokers after 1 month. There was a positive correlation between leptin/BMI and leptin/%BF with the QSU-Brief (Factor 2) of 1 month in women who remained smokers (r=0.565; p=0.023) and the QSU-Brief (Factor 2) initial among the abstinent women (r=0.551; p=0.033). The highest concentrations of leptin were associated with greater craving and difficulty in achieve abstinence.