Lacticaseibacillus rhamnosus modulates MAPK-associated inflammatory programs via soluble factors
Microbial communities colonize nearly all mammalian body surfaces and contribute critically to organ homeostasis and immune regulation. The lungs, once considered sterile, are now recognized to harbor a resident microbiota that influences lung development and immunity. While environmental factors shaping lung microbiota composition have been extensively studied, the contribution of host genetic factors remains less understood. Recent studies have linked lung abundance of Lactobacillus to host genomic regions containing Mk2 and Il10, two key regulators of inflammatory signaling. Here, we investigated whether selected Lactobacillus taxa modulate epithelial inflammatory responses through MK2-associated pathways under basal and inflammatory conditions. Human lung epithelial A549 cells were co-cultured with four Lactobacillus taxa (Lacticaseibacillus rhamnosus, Limosilactobacillus reuteri, Lactiplantibacillus plantarum, and Ligilactobacillus murinus). Inflammatory conditions were modeled using lipopolysaccharide (LPS) challenge. Transcriptome-wide effects were examined by RNA-seq, comparing live bacteria, heat-killed supernatants, and heat-killed pellets.