Marija Stanković*, Hristina Mitrović, Svetlana Soković-Bajić, Katarina Veljović, Natasa Golić
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia
marijast [at] imgge.bg.ac.rs
Abstract
Although low density features lung microbiota, its composition is crucial for the development and maintenance of healthy human lungs. In chronic obstructive pulmonary disease (COPD) lung microbiota is changed, correlating with the disease severity and exacerbations. But whether changed lung microbiota causes COPD, or microbiota changes due to disease is unclear. Moreover, the effect of COPD on microbes is unknown.
We aimed to scrutinize the effects of interspecies interaction between healthy and diseased human bronchial epithelial cells with bacteria featured by preferred properties, Lactiplantibacillus plantarum BGPKM22, by dual RNA sequencing.
Primary healthy and diseased bronchial epithelial cells, from a healthy subject and COPD patient, respectively, were exposed to Lactip. plantarum BGPKM22. Dual RNA sequencing and data processing were performed by Novogene (Beijing, China). Clean reads were aligned to the human genome and Lactip. plantarum SK151 using Hisat2 tool. Differential gene expression analysis was performed using the edgeR R package. The adherence of BGPKM22 to the cells and its resistance to oxidative stress were determined.
In healthy and diseased cells interaction with BGPKM22 caused a change in expression of 52 and 45 genes, respectively. The genes IQCN, LINC01554, KCNB1, and CDK7 indicated a specific response of human bronchial epithelial cells exposed to BGPKM22, regardless of the health status. Markedly more genes showed a change in expression in BGPKM22 in interaction with healthy than with diseased cells, 486 and 101, respectively. The adhesion of BGPKM22 was better to healthy than to diseased cells. The fitness of BGPKM22 increased only after interaction with healthy cells.
Utilization of BGPKM22 can alleviate symptoms and replenish diminished lung microbiota in COPD. Preferential affinity of BGPKM22 towards healthy cells can explain diminished lung microbiota in COPD. Beneficial effects of BGPKM22 can remain unexploited by host due to decreased affinity and fitness of BGPKM22 in interaction with diseased cells. Abundant response of BGPKM22 in interaction with healthy cells, sheds a new light on potential lung probiotics depending on the host state.
Keywords: primary human bronchial epithelial cells, Lactiplantibacillus plantarum BGPKM22, interspecies interaction, dual RNA sequencing
Acknowledgement: This research was funded by the Science Fund of the Republic of Serbia, grant PROMIS, #6066974 LABLUNG.