Host-Symbiont Interactions in the Mammalian Lung
The human body hosts diverse microbial communities colonizing every surface. The commensal microbes that populate the gut, skin, and lung are now recognized for their role in maintaining organ homeostasis. Despite the lung being previously considered sterile in healthy individuals, it is now understood that they harbor a microbial community that plays an essential role in lung development and immunity. In this thesis, we aimed to contribute to a more comprehensive understanding of the role played by host genetics in the shaping of lung microbiota composition.
In Chapter 1, I employed the in vitro cell culture system to further examine a proposed link between the Lactobacillus and the mouse Mk2 and Il10 genes. By analyzing candidate host genes and performing RNA-seq, potential probiotic Lactobacillus species for use in humans and mice were identified. The candidate species appear to interact with the host, thereby mitigating the inflammatory response via the MK2 and JNK1 pathways. Both Lactobacillusrhamnosus and Lactobacillusmurinus are presented as excellent candidates for further investigation.
In Chapter 2, an in vivo Mk2 knockout mouse model was employed for the characterization of the lung and gut microbiota. The gut microbiota was found to exhibit taxa with differential abundance according to Mk2 genotype. A comparison of the microbiota from the two body sites revealed the presence of shared taxa, suggesting a gut-lung axis.
In Chapter 3, I present evidence that the selection of an extraction kit can introduce biases in the interpretation of microbial composition in such low biomass environments. The findings highlight the limitations of current methodologies and the inability to clearly identify contaminant taxa. Contaminants that are specific to the kit in question were identified.
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