The Role of Probiotic Lactobacillus in Immune Regulation and Modulation of the Vaginal Microbiota During Pregnancy

Preterm birth (PTB) occurs in 10% of all pregnancies globally. Premature babies have a mortality rate 40 times higher than term infants. Approximately 25-30% of PTB can be attributed to intrauterine infection/inflammation. A disturbance of the vaginal microbiota as observed in bacterial vaginosis (BV) is associated with an increased risk of PTB. Treatment of preterm labor with antibiotics is largely ineffective, and probiotic lactobacilli have been proposed as a potential preventive therapy for BV and PTB. The objectives of this thesis were to assess 1) the effect of Lactobacillus rhamnosus GR-1 (GR-1) and its supernatant (GR-1 SN) on the prevention of lipopolysaccharide (LPS)-induced PTB and systemic and intra-uterine cytokine and chemokine profiles in pregnant CD-1 mice, 2) the effect of GR-1 on the mouse vaginal microbiota, and 3) the effect of GR-1 and L. reuteri RC-14 on the cervico-vaginal cytokine profile and vaginal microbiota in pregnant women with an abnormal Nugent score. Pregnant mice were pre-treated with intra-peritoneal injections of GR-1 SN or oral GR-1 live bacteria prior to intrauterine injection of LPS in two separate studies. The expression of cytokines and chemokines in the maternal plasma, amniotic fluid and intrauterine tissues were then measured. The vaginal microbiota was also determined in animals treated with oral GR-1 live bacteria. Pre-treatment with GR-1 SN, but not with GR-1 live bacteria, reduced LPS-induced PTB and inflammation in pregnant mice. The vaginal microbiota of pregnant mice was altered with oral GR-1 live bacteria. A randomized, double blind placebo-controlled trial was conducted, in which pregnant women with an abnormal Nugent score in their first trimester of pregnancy received orally either placebo or GR-1 and RC-14 for 12 weeks. Their cervico-vaginal cytokine profile and vaginal microbiota was then determined. Oral GR-1 and RC-14, at the dose and duration used, did not change the cytokine profile and vaginal microbiota of pregnant women with an abnormal Nugent score. We conclude that L. rhamnosus GR-1 supernatant, but not the live bacteria, may have the potential to serve as a prophylactic therapy for inflammation-associated conditions during pregnancy, including PTB.Ph.D