Page 61 - MI-2-3

Microbes & Immunity Understanding lung development, health, and diseases

cells. The differentiation of T helper (Th) cells into two In recent years, probiotics have shown promise in
subsets, Th1 and Th2, each producing unique cytokines the treatment of asthma. Studies employing organisms
and triggering unique immune responses, is referred to from the genera Bifidobacterium and Lactobacillus
as polarization. Th2 cells predominate in the immune have shown promising anti-inflammatory properties,
system before birth. Following birth, naive T lymphocytes along with reductions in mucus production and airway
in the lungs undergo a polarization shift from a Th2 to a hyperresponsiveness. 62
Th1 phenotype, which helps prevent allergic disorders and
newborn asthma. 58 6.2.2. COPD
The polarization of T cells is largely determined by COPD is an obstructive lung condition characterized by
cytokines. The presence of interleukin (IL)-12 and/or inadequate airflow. Research has shown that, in contrast
interferon γ (IFN-γ) promotes polarization toward Th1 to asthma patients who exhibit notable alterations in their
cytokine production, whereas IL-4 promotes polarization lung microbiota even in the early stages of the illness,
toward Th2 cytokine secretion. patients with mild-to-moderate COPD possess lung
microbiota very similar to that of healthy individuals.
63
Throughout the first 2 weeks of life, the bacterial Alterations in lung microbiota become evident only in
phyla Gammaproteobacteria and Firmicutes give way to advanced stages of COPD, whereas Actinomycetes species
Bacteroidetes in the lungs. These microbiome alterations are more common in mild-to-moderate COPD. In more
are associated with programmed death ligand 1 (PD-L1)- severe cases, the microbial shift found in asthma patients is
dependent growth of Helios-negative regulatory T characterized by a decrease in Bacteroidetes and an increase
cells (Tregs) in the lungs. Inhibition of PD-L1 or loss of in Proteobacteria or Firmicutes. 63,64 However, given that
microbiota leads to a heightened inflammatory response asthma and COPD are distinct illnesses, this suggests that
to allergens persisting into adulthood. 59 factors other than the microbiota composition may play a
For instance, amphiregulin produced by Tregs protects more important role in disease development. 64
lung tissue after inflammation caused by viruses. Loss of Furthermore, it has been demonstrated that cigarette
54
C-C motif chemokine receptor 7 affects Treg homeostasis smoke extract stimulates the release of chemokines and
and trafficking within the lungs, which further impacts pro-inflammatory cytokines in both human and animal
55
wound healing in pulmonary fibrosis. Furthermore, epithelial cells. Probiotics may reduce the inflammatory
CD73-dependent adenosine synthesis by Tregs contributes response in COPD by strengthening the tolerance of
to the recovery from acute lung injury. Tregs also aid in epithelial cells to the harmful effects of cigarette smoke
56
limiting damage by lowering allergic airway inflammation extract. 65
and disrupting the epithelial barrier in house dust mite-
derived protease-induced allergy diseases. 6.2.3. CF
6.2. Lung microbiota in diseases CF is a prevalent autosomal recessive genetic disorder that
primarily impacts the lungs, leading to thickened secretions,
Certain illnesses may feature disturbances in the balance altered microbiota diversity, and increased susceptibility to
of lung microbiota. This includes, but is not limited to, 66
asthmatic conditions, COPD, IPF, cystic fibrosis (CF), infections due to progressive airway colonization. There
COVID-19, and influenza. is ongoing debate regarding the relationship between CF
pathophysiology and the lung microbiome, particularly
6.2.1. Asthma concerning respiratory pathogens such as Staphylococcus
aureus and Pseudomonas aeruginosa. In addition,
Asthma is a chronic, complex condition impacted by alterations in the gut microbiome have also been observed
environmental factors such as allergens and air pollution, in CF patients. 67
as well as hereditary factors. It is more prevalent in
industrialized nations, where the diversity and composition However, some studies have shown that antibiotic
of the lung microbiota are influenced by living conditions, treatment does not significantly impact disease progression.
which in turn greatly influences the disease onset. Studies Clinical investigations have explored the effectiveness
have demonstrated that asthma patients exhibit different and safety of probiotics in improving health outcomes
lung microbiota than healthy individuals, with a lower for CF patients. Common probiotic strains used in
68
prevalence of Bacteroidetes and a higher prevalence of these studies include Lactobacillus spp., Bifidobacterium
Proteobacteria. 60,61 As a result, the development and course spp., Saccharomyces spp., and Streptococcus spp., typically
66
of asthma are heavily dependent on the composition of the administered as single or multi-strain formulations. These
lung microbiota and its interaction with the host. studies found that probiotics can reduce fecal calprotectin

Volume 2 Issue 3 (2025) 53 doi: 10.36922/mi.7719