A Combination of Lacticaseibacillus paracasei CECT 30660 and Bifidobacterium longum subsp. infantis CECT 7210 Cell-Free Supernatants Reduces LPS-Induced Preterm Birth and Systemic Inflammation in Pregnant Mice

<b>Background/Objectives.</b> Preterm birth (PTB), affecting approximately 11.1% of pregnancies globally, often results from inflammation at the maternal-fetal interface triggered by microbial or immune dysregulation. This study investigates the efficacy of cell-free supernatant derived from <i>Bifidobacterium longum</i> subsp. <i>infantis</i> CECT 7210 and <i>Lacticaseibacillus paracasei</i> CECT 30660 in mitigating inflammation-induced PTB in a murine model. <b>Methods.</b> Lipopolysaccharide (LPS) was administered to induce preterm labor and systemic inflammation, mimicking infection-related PTB. <b>Results.</b> The results demonstrated that combined administration of CECT 7210 and CECT 30660 cell-free supernatants reduced preterm deliveries from 85.6% to 42.8% in mice and significantly attenuated systemic and intrauterine proinflammatory cytokines, including TNF-α and IL-6, in maternal plasma and myometrial tissues. Importantly, this anti-inflammatory effect was independent of maternal progesterone or oxytocin levels, suggesting a direct modulation of immune responses in this animal model. The cell-free supernatant combination also inhibited the growth of pathogenic bacteria, including <i>Streptococcus agalactiae</i>, highlighting its antimicrobial potential. <b>Conclusions.</b> This study underscores the potential of CECT 7210 and CECT 30660 cell-free supernatants as a therapeutic strategy to reduce the risk of PTB by targeting inflammation pathways. The findings pave the way for further preclinical and clinical research to validate the efficacy of these cell-free supernatants in preventing PTB and associated complications, offering a promising alternative to traditional probiotic approaches.