Does the Human Placenta Delivered at Term Have a Microbiota? (21) The human placenta has traditionally been viewed as sterile, and colonization of the placenta by microorganisms has been associated with adverse pregnancy outcomes. Yet, recent reports employing DNA sequencing techniques have reported that the human placenta at term contains a unique microbiota. However, when studying low microbial biomass samples, sequence-based approaches can capture background contaminating DNA from DNA extraction kits, PCR reagents, and laboratory environments. Therefore, the objective of this study was to determine whether the human placenta delivered at term in patients without labor undergoing Cesarean delivery harbors a resident microbiota. This was a cross-sectional study of placentas from 29 women who had a Cesarean delivery without labor at term. The study included technical controls to account for potential background contaminating DNA. The bacterial profiles of placental tissues and background technical controls were characterized and compared using bacterial culture, quantitative real-time PCR, 16S rRNA gene sequencing, and metagenomic surveys. Twenty-eight of 29 placental tissues were negative for bacterial culture. The few bacteria cultured from the remaining sample were likely laboratory contaminants because corresponding 16S rRNA genes from the cultivars were not detected in the same placental sample. Quantitative real-time PCR did not indicate greater abundances of bacterial 16S rRNA genes in placental tissues than in background technical controls. Furthermore, 16S rRNA gene sequencing did not reveal consistent differences in the composition or structure of bacterial profiles between placental samples and background technical controls. Most of the bacterial sequences obtained from metagenomic sequencing of placental tissues were from cyanobacteria, aquatic bacteria, or plant pathogens; the placenta is therefore unlikely to provide a suitable ecological niche for these bacteria and, as such, these data are not likely indicative of a placental microbiota. In summary, a resident microbiota could not be identified in human placentas delivered at term from women without labor using multiple modes of microbiologic inquiry. A consistently significant difference in the abundance and/or presence of a microbiota between placental tissue and background technical controls could not be found. This study demonstrates that incorporating technical controls for potential sources of background contaminating DNA into studies of low microbial biomass samples, such as the placenta, is necessary for deriving reliable conclusions about host-associated microbiota. Progesterone Treatment Prevents Preterm Labor and Birth Induced by Effector and Activated T Cells (1): Preterm birth is the leading cause of perinatal morbidity and mortality worldwide, which is commonly preceded by spontaneous preterm labor. Multiple etiologies have been associated with preterm labor; yet, only pathological inflammation has been causally linked to preterm birth. Pathological inflammation can be acute or chronic in nature. Most research has focused on the mechanisms whereby the maternal innate immune system induces acute inflammation, leading to preterm labor and birth. However, the role of the maternal adaptive immune system, specifically T cells, in the pathogenesis of preterm labor and birth was poorly understood. In the above-mentioned study, we utilized human tissues and animal models to investigate a causal link between maternal T cell activation and preterm labor and birth. First, by performing exhaustive immunophenotyping of the decidual tissues, we found that effector and activated T cells are present at the human maternal-fetal interface. Importantly, these cells were enriched in women who underwent spontaneous preterm labor and birth. Next, using a murine model of in vivo T cell activation, we reported that the activation of maternal T cells induces preterm birth and adverse neonatal outcomes. The mechanisms whereby the activation of T cells induces preterm birth included stereotypical immune responses at the maternal-fetal interface as well as in the mother and the fetus, which were different from those initiated by microbial products (e.g. endotoxin) or progesterone withdrawal function (e.g. treatment with RU486). We also show that activation of T cells induces pro-inflammatory responses in the myometrium and cervix. Lastly, we showed that pre-treatment with progesterone, a clinically proven strategy, has systemic and local anti-inflammatory effects preventing preterm birth and adverse neonatal outcomes. Collectively, the findings reported in this study provide the first mechanistic demonstration showing a role for maternal effector and activated T cells in the pathophysiology of preterm labor and birth. Antibiotics can Eradicate Intra-Amniotic Infection or Inflammation (24): This is a case series study in which 50 women with singleton gestations between 20-34 weeks, preterm labor with intact membranes, and evidence of intra-amniotic infection or inflammation by analysis of amniotic fluid obtained by abdominal amniocentesis received an antibiotic treatment that consisted of ceftriaxone, clarithromycin, and metronidazole. Follow-up amniocentesis was performed in 19 of 29 patients who were undelivered for 7 days. Treatment success was defined as resolution of intra-amniotic infection/inflammation or delivery 37 weeks. Resolution of intra-amniotic infection/inflammation was confirmed in 79% of patients (15/19) who had a follow-up amniocentesis. Treatment success occurred in 84% of patients (16/19) who had a follow-up amniocentesis and in 32% of patients (16/50) who received the antibiotic regimen. In conclusion, the administration of antibiotics to patients with preterm labor and intact membranes with proven intra-amniotic infection/inflammation is associated with eradication of infection and inflammation in a subset of patients.
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