Probiotic Lactobacillus kefiri CIDCA 8348 administration prevents LPS-induced preterm birth by reducing acute inflammation in gestational tissues and favoring placental vascular homeostasis

VENTIMIGLIA MS; POZO ALVAN MI; VALEFF NJ; JURIOL LV; SERRADELL MA; JENSEN CF

Buenos Aires

Congreso; International Federation of Placenta Associations (IFPA) - 8th Latin American Symposium on Maternal-Fetal Interaction and Placenta; 2019

IFPA

Objectives: Preterm birth (PTB) is a recurrent complication of pregnancyaffecting 5-18% of all births worldwide and leading to serious consequences for the mother and the progeny. Although etiology is not fully determinated, it is known that inflammation is a contributing factor to both infection-mediated and spontaneous PTB. This process involves events characteristic of a progressively inflammatory cascade within the fetal membranes, uterus and cervix and is accompanied by a massive influx of leukocytes. We have previously reported that treatment with Lactobacillus Kefiri CIDCA 8348 (LK-48) completely prevented PTB (100%) in a lipopolysaccharide (LPS)-induced PTB mice model. Given this, wesought to elucidate the mechanisms behind LK-48 protective effect in PTBinduction.Methods: C57BL/6 females were administered every 48h by oral gavage during a week with probiotic (PB-LK-48) (108 CFU) or vehicle (milk). Afterward, animals were mated with BALB/c males. Day of the vaginal plug detection was considered day 0.5 of pregnancy. Treatment continued every 48h during pregnancy and females were challenged with LPS (10 ug/mice; i.p) on g.d. 16.5 (~3 days before expected on-time birth). Tissue samples from uterus, placenta, decidua and cervix were harvest at different times after LPS challenge (5h, 12h and 18h). Neutrophils (Ly6G), CD8 T lymphocytes and natural killer lymphocytes (NK1.1) influx was evaluated by flow cytometry. In addition, histological examination by light microscopy was performed.Results: Treatment with LK-48, significantly lowered leucocytes influx induced by LPS in uterine, placental and decidual tissues. Histological studies confirmed these findings. Significantly lower numbers of neutrophils were observed both in cervical and endometrial mucosa as well as in placental tissues. Furthermore, PB treatment ameliorated changes in macro and microcirculation including blood stasis and vasodilation, thickening of capillary and sinusoidal walls with multiple foci of microhemorrhages in placenta.Conclusion: Overall, our results demonstrate that probiotic LK-48administration prevents LPS-induced PTB by reducing leucocytes influxinto gestational tissues and promoting placental vascular homeostasis.