Abstract Background Probiotics are emerging modulators of immune function with evidence supporting their ability to attenuate inflammation across multiple organ systems, including the lungs. By shaping host immunity through microbiota-derived signals, they represent potential therapies for chronic inflammatory disease. However, their effects on lung-specific inflammation under immune dysregulation remain unclear. Regulatory T-cell (Treg) deficiency, modeled in Foxp3 mutant scurfy (SF) mice, causes systemic and pulmonary inflammation resembling human IPEX (Immunodysregulation, Polyendocrinopathy, Enteropathy, X-linked) syndrome. Objective To investigate the effect of probiotic Limosilactobacillus reuteri DSM 17938 on lung inflammation and transcriptomic expression of 790 inflammation-related genes in SF mice. Methods We studied four groups of mice to evaluate the impact of probiotic intervention on pulmonary inflammation. SF mice B6. Cg-Foxp3ˢf/Y^, a model of Treg deficiency, received Limosilactobacillus reuteri DSM 17938 (107 CFU/day) starting on day 8 of life (SFL group, n = 6). A second SF group received control media (SFC, n = 7). Wild-type mice received either control media (WTC group, n = 5), or probiotic supplementation (WTL group, n = 6). Biospecimens were collected on day 21. Pulmonary inflammation was assessed via lung transcriptomics using the NanoString nCounter platform (790 inflammation-related genes) and by histological lung injury scores (LIS). Results SF mice treated with Limosilactobacillus reuteri DSM 17938 showed significant downregulation of pulmonary inflammatory gene signatures and lower abundance of neutrophils, CD45+ cells, NK cells, Th1 cells, and T cells compared to SFC. Transcriptomic analysis revealed upregulation of B-cell-related genes in SFL vs SFC mice. Probiotic treatment suppressed key inflammatory pathways, including cytokine signaling, apoptosis, chemokine activity, Th1/Th2/Th17 and Toll-like receptor pathways. Cytokine levels were markedly reduced in the SFL group. Similar suppression occurred in WTL vs WTC mice, though fewer genes were affected. WTC mice exhibited higher CD45+, NK, B, CD8+ T, mast, and NK CD56ᵈim^ cells than WTL. Histological LIS analysis confirmed decreased pulmonary inflammation in probiotic-treated mice, evidenced by reduced alveolar septal thickening. Conclusions Limosilactobacillus reuteri DSM 17938 reduced pulmonary inflammation in Treg-deficient mice, supporting its probiotic potential. It modulated immune gene expression bidirectionally, downregulating some inflammatory pathways while upregulating others, highlighting the complexity of host-microbiota interactions. This abstract is funded by: None
Mosquera et al. (Fri,) studied this question.