Oral Probiotic Lactobacillus kefiri prevents Lipopolysaccharide-induced preterm birth, reduces inflammation and modulates the vaginal microbiota inpregnant mice

Abstract

Abstract Prevention and treatment of preterm birth (PTB) are an unresolved global challenge in obstetric care. Human PTB is defined as delivery prior to 37 weeks of gestation. It is known that inflammation is a contributing factor where an inflammatory cascade within the gestational tissues followed by a massive influx of leukocytes takes place. The efficacy of actual interventions are largely unsatisfactory. We have shown that treatment with probiotic Lactobacillus Kefiri (Lk) completely prevented PTB (100%) in a lipopolysaccharide (LPS)-induced PTB mice model. Given this, we sought to elucidate the mechanisms behind PB-Lk protective role in PTB induction. C57BL/6 females were oral treated every 48h during a week with Lk or vehicle before being mated with BALB/c males and during pregnancy. Females were challenged with LPS on gd 16 (~3 days before expected term). Samples from gestational tissues were harvest 18 h after LPS. Leukocytes influx was evaluated by flow cytometry. Metalloproteinase-9 activity was measured by zymography. In addition, histological examination by light microscopy was performed. The impact on vaginal microbiota was evaluated by a qualitative analysis (PCR-DGGE). Treatment with Lk, significantly lowered leucocytes influx induced by LPS as well as MMP-9 activity. Histological studies confirmed these findings. In placenta, Lk treatment ameliorated changes in micro and macrocirculation and DGGE profiles allowed differentiation of groups in two clusters, suggesting that Lk induced changes in the vaginal community composition. Our results demonstrate that Lk administration may have the potential to serve as a prophylactic therapy for inflammation-associated conditions during pregnancy, including PTB.