The lung microbiota, is the pulmonary microbial community consisting of a complex variety
of microorganisms found in the lower respiratory tract particularly on the mucous layer and
the epithelial surfaces.
These microorganisms include bacteria, fungi, viruses and bacteriophages.
The bacterial part of the microbiota has been more closely studied.
It consists of a core of nine genera: Prevotella, Sphingomonas, Pseudomonas, Acinetobacter,
Fusobacterium, Megasphaera, Veillonella, Staphylococcus, and Streptococcus.
They are aerobes as well as anaerobes and aerotolerant bacteria.
The microbial communities are highly variable in particular individuals and compose of about
140 distinct families.
The bronchial tree for instance contains a mean of 2000 bacterial genomes per cm2 surface.
The harmful or potentially harmful bacteria are also detected routinely in respiratory
specimens.
The most significant are Moraxella catarrhalis, Haemophilus influenzae, and Streptococcus
pneumoniae.
They are known to cause respiratory disorders under particular conditions namely if the
human immune system is impaired.
The mechanism by which they persist in the lower airways in healthy individuals is unknown.
Fungal genera that are commonly found in the lung microbiota include Candida, Malassezia,
Neosartorya, Saccharomyces, and Aspergillus, among others.
== Role of the epithelial barrier == The airway epithelium together with alveolar
macrophages and dendritic cells play a major role in the initial recognition of bacterial
products getting into the lower airways with the air.
Since some of these products are potent proinflammatory stimuli it is extremely important for the
immune system to distinguish between pathogens and non-pathogenic commensals.
This prevents the development of constant inflammation and forms tolerance against harmless
microbiota.
This process becomes much more intriguing when taking into account that commensals often
share their surface molecules with pathogens.
Epithelial cells are equipped with very sensitive recognition tools - toll like receptors (TLRs),
nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) and retinoic acid-inducible
gene (RIG)-I-like receptors (RLRs) which recognize a broad variety of microbial structural components.
After recognition of pathogenic bacteria proinflammatory pathways are activated and cellular components
of the adaptive and innate immunity are recruited to the infection site.
One key regulator in this process is the NF-κB which translocates from the cytoplasm into
the nucleus and activates pro-inflammatory genes in epithelial cells and macrophages.
The DNA-binding protein complex recognizes a discrete nucleotide sequence (5’-GGG ACT
TTC T-3’) in the upstream region of a variety of response genes.
The activation of NF-κB by a number of stimuli: bacterial cell walls or inflammatory cytokines
results in its translocation to the nucleus.
In contrast, harmless bacteria do not cause the translocation of NF-κB into the nucleus
thus preventing the inflammation although they can express the same microbe-associated
molecular patterns (MAMPs).
One possible mechanism explaining this effect was suggested by Neish showing that non-pathogenic
S. typhimurium PhoPc and S. pullorum are able to prohibit the ubiquitination of NF-κB inhibitor
molecule nuclear factor of NF-κB light polypeptide gene enhancer in B-cells inhibitor alpha (IκB-κ).
Another explanation of commensal tolerance of the epithelium refers to the post-translational
modification of a protein by the covalent attachment of one or more ubiquitin (Ub) monomers.
The inhibition of ubiquitination leads to reduction of inflammation, because only polyubiquitinated
(IκB-κ is targeted for degradation by the 26 S proteasome, allowing NF-κB translocation
to the nucleus and activation the transcription of effector genes (for example IL-8).
Probiotic bacteria such as Lactobacilli are able to modulate the activity of the Ub-proteasome
system via inducing reactive oxygen species (ROS) production in epithelial cells.
In mammalian cells, ROS have been shown to serve as critical second messengers in multiple
signal transduction pathways in response to proinflammatory cytokines.
Bacterially induced ROS causes oxidative inactivation of the catalytic cysteine residue of Ub 12
resulting in incomplete but transient loss of cullin-1 neddylation and consequent effects
on NF-κB and β-catenin signaling.
Another commensal species, B. thetaiotaomicron, attenuates pro-inflammatory cytokine expression
by promoting nuclear export of NF-κB subunit RelA, through a peroxisome proliferator activated
receptor γ (PPAR-γ)-dependent pathway.
PPAR-γ target transcriptionally active Rel A and induce early nuclear clearance limiting
the duration of NF-κB action.
The balance between pathogens and commensals is extremely important in the maintenance
of homeostasis in the respiratory tract.
== Physiology == The airways are continually exposed to a multitude
of microorganisms, some of which are able to persist and even colonize respiratory tract.
This is possible due to the presence of nutrients, oxygen, and optimal growth temperature.
There are several host-derived nutrient sources for microbial residents: secretions from airway
epithelial cells (especially goblet cells), secretions from submucosal glands and transudate
from plasma.
Moreover, the pool of available nutrients is increased by the activities of some members
of the microbiota.
Macromolecular components of respiratory secretions (proteins, glycoproteins, lipids, nucleic
acids) are converted to nutrients (e.g. carbohydrates, amino acids).
Thus, the metabolic activity of present bacteria allow for the colonization of new species.
The commensal bacteria are nonpathogenic and defend our airways against the pathogens.
There are several possible mechanisms.
Commensals are the native competitors of pathogenic bacteria, because they tend to occupy the
same ecological niche inside the human body.
Secondly, they are able to produce antibacterial substances called bacteriocins which inhibit
the growth of pathogens.
Genera Bacillus, Lactobacillus, Lactococcus, Staphylococcus, Streptococcus, and Streptomyces
are the main producers of bacteriocins in respiratory tract.
Moreover, commensals are known to induce Th1 response and anti-inflammatory interleukin
(IL)-10, antimicrobial peptides, FOXP3, secretory immunoglobulin A (sIgA) production.
== Clinical significance == Changes in microbial community composition
seem to play a role in progression of such pulmonary disorders as chronic obstructive
pulmonary disease (COPD), asthma, and cystic fibrosis.
In humans, S. aureus is part of the normal microbiota present in the upper respiratory
tract, and on skin and in the gut mucosa.
S. aureus, along with similar species that can colonize and act symbiotically but can
cause disease if they begin to take over the tissues they have colonized or invade other
tissues, have been called "pathobionts".
MRSA can similarly colonize people without making them sick.
The presence of such genera as Mycoplasma, Pseudomonas, and Staphylococcus is correlated
with stable COPD state.
On the other hand, Prevotella, Mesorhizobium, Microbacterium, Micrococcus, Veillonela, Rhizobium,
Stenotrophomonas, and Lactococcus present mostly in healthy individual cohort.
The relative abundance of Proteobacteria is increased in asthmatic children.
Pseudomonas aeruginosa, Staphylococcus aureus, and Burkholderia cepacia are found most often
in cystic fibrosis patients.
High-throughput sequencing and the whole genome sequencing approaches will provide the further
information about the complexity and physiological implication of commensal bacteria in the lower
respiratory tract.
== See also == Human microbiome
List of human flora Bacteriocin