Asthma and obesity are common inflammatory diseases that are mediated by specific immune features. For example, asthma is associated with a Th2 response, while obesity is associated with a Th1/Th17 profile.
When these immunological features are combined, more severe asthmatic reactions occur with greater frequency. Recently, changes in immune traits, in relation to obesity and asthma, have been linked to changes in an individual’s microbiome.
newly Immunology Letters The study provides evidence of a possible trigger for childhood asthma. Moreover, this study summarizes the mechanisms associated with asthma exacerbating obesity and describes the role of maternal obesity in the formation of the gut and lung microbiota of the offspring, which leads to the development of asthma.
Stady: Asthma, obesity, and the microbiome: a complex immune interaction. Image credit: monofaction/Shutterstock.com
The immunological association between asthma and obesity
Asthma is a chronic inflammatory disease of the lungs, leading to recurrent episodes of airway hyperresponsiveness (AHR). Some of the common symptoms associated with this disease include wheezing, coughing, chest tightness, and shortness of breath.
Chronic inflammation can cause a gradual loss of lung function, which can be a life-threatening event. According to a recent report, 18% of the world’s population suffers from asthma.
Atopic asthma is the most common form of the disease, and it has a strong genetic predisposition to produce large amounts of asthma antigenImmunoglobulin E (IgE) in response to an allergen. Upon exposure to an allergen, enzymes such as thymic stromal lymphoietin (TSLP), as well as interleukin 25 (IL-25) and IL-33, are produced in exposed subjects. Then, these alarms activate innate lymphocytes (ILC)2, dendritic cells (DCs), basophils, and mast cells.
Antigen-bearing DCs travel to the lymph nodes and naive helper T cells (Th)2 cells, which produce cytokines such as IL-4, IL-5 and IL-13, in addition to T helper (Tfh) cells. Ultimately, these events convert IgM to IgE by B cells. Mast cells are encapsulated with IgE, which is degraded upon subsequent exposure to the allergen.
Cytokines produced by activation of Th2 cells and mast cells cause bronchoconstriction, mucus hypersecretion, and eosinophil recruitment. Successive exposure leads to tissue damage and a gradual loss of lung function.
Obesity is an abnormal accumulation of fat, which is described by a body mass index (BMI) equal to or greater than 30 kg/m.2. Several meta-analysis studies have shown a positive association between obesity and asthma severity. Obesity not only accelerates recurrent asthma attacks, but also reduces response to conventional treatment.
that in vivo The study reports asthma exacerbated by obesity in BALB/c mice, in which decreased levels of IgE and increased IFN-g were observed. Notably, another study demonstrated that children with obesity and asthma share DNA methylation patterns associated with macrophage activation, non-atopic inflammation, and Th1 polarization, and thus possess a hypomethylated profile on the IL2RA, CCL5, and TBX21 genes.
Genetic and environmental factors associated with asthma and obesity
Although many environmental factors have been linked to the development of obesity and asthma, important genetic factors have also been discovered for these diseases. For example, polymorphisms of the β3-adrenergic receptor, which is present in adipose tissue, have been linked to obesity and severe asthmatic symptoms. Another factor associated with the incidence of obesity, AHR, and asthma is tumor necrosis factor (TNF)-α haploidy.
Notably, the structural features of the obese body also indicate respiratory physiology. The accumulation of fat in the abdomen and chest reduces lung function by inhibiting the movement of the diaphragm. It also enhances pleural pressure and reduces lung compliance.
Obese adults typically show poorer performance on pulmonary function tests (PFTs), such as forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and total lung capacity (TLC).
In addition to genetic and mechanistic factors, smoking, air pollution, viral infection, and host factors including age, gender, and obesity influence the incidence of asthma. Thus, obesity can be considered a risk factor for developing asthma.
Asthma, obesity and germs interactions
Several studies have hypothesized that exposure to microorganisms reduces the risk of allergic disease. Indeed, early exposure to bacterial endotoxins leads to the development of atopy and sensitization, which protects the individual from allergic reactions.
There are a large number of microbes in the host tissue (the microbiota) that have a symbiotic relationship with the host. Bacteroidetes and Firmicutes are the major groups of bacteria found in host cells, in addition to other bacterial phyla including Fusobacteria, Actinobacteria, Verrucomicrobia, and Proteobacteria. These bacteria play a key role in trophic metabolism that stimulates immune system maturation, modulates immunity, and protects the host from harmful pathogens.
Diets high in saturated fats and carbohydrates, as well as low in fiber, cause microbial imbalance (dysbiosis), which increases the risk of inflammatory diseases including asthma and obesity. Such diets mostly reduce Bacteroidetes, an important source of short-chain fatty acids, and increase Firmicutes taxa that affect low-grade systemic inflammation and endotoxemia.
Maternal obesity is closely related to the incidence of asthma in children. Maternal obesity impairs fetal lung development by reducing fetal glucocorticoid synthesis, which is an essential component of lung maturation and the structure of fetal alveoli. In addition, newborns of obese mothers show increased leptin and C-reactive protein levels in cord blood, which is also associated with an increased risk of asthma.
- Menegati, M.L., Esteves de Oliveira, E., de Castro Oliveira, B., et al. (2023) Asthma, obesity, and the microbiome: a complex immune interaction. Immunology Letters. doi: 10.1016/j.imlet.2023.01.004