Multi-omics analysis of glutamine and fish collagen peptides in alleviating post-antibiotic Streptococcus pneumoniae injury in feline lung cells.

Streptococcus pneumoniae (SP) infection often leads to persistent lung injury even after antibiotic treatment. Despite this phenomenon, the mechanisms underlying host cell recovery remain poorly understood. Upon breaching the epithelial barrier, SP primarily targets the pulmonary interstitial cells, which constitute the major mesenchymal component of the lung. These cells serve as essential effectors of tissue repair, extracellular matrix remodeling and epithelial restoration. Therefore, a feline pulmonary interstitial cell (FCA-L2) model of SP infection was established to investigate the protective effects of glutamine (GLU) and fish collagen peptides (FCP) through integrated transcriptomic and metabolomic analyses. Cells were infected with SP (0.05 McFarland units for 4 h) and then treated with doxycycline (7.5 µg/ml for 18 h) followed by GLU (40 mM) or FCP (500 µg/ml). Notably, SP infection increased lactate dehydrogenase (LDH) release by 3.5-fold, induced secretion of IL-1β, TNF-α and IL-8, disrupted tight-junction proteins (claudin, ZO-1 and occludin) and caused oxidative imbalance and apoptosis despite antibiotic (doxycycline) treatment. However, treatment with GLU or FCP significantly reduced LDH release by ~40%, restored junctional proteins, suppressed inflammatory cytokines and enhanced antioxidant enzyme activities. Multi-omics analysis revealed that GLU promoted amino acid biosynthesis and energy metabolism and suppressed aminoacyl-tRNA synthetases and cell-cycle regulators, thereby enhancing metabolic adaptability. By contrast, FCP activated amino and nucleotide sugar metabolism, increased polyunsaturated fatty-acid synthesis and supported glycocalyx repair and membrane reconstruction. GLU and FCP provided complementary metabolic and structural protection, which mitigated post-infectious stress and promoted cellular recovery. The findings of the present study underscore the potential of bioactive food-derived compounds as adjunctive therapies that may accelerate lung tissue repair and enhance the efficacy of conventional antibiotics.