Lactobacillus Reuteri Feasibility Study on Probiotic Treatment and Perinatal Microbiome

Study Overview
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Brief Summary
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Investigators want to investigate if the Lactobacillus Reuteri (probiotic bacteria) given to pregnant women can be found in different maternal compartments and in the first stool and oral swab collected immediately after birth of a newborn delivered by cesarean delivery. Investigators also want to explore if exposure to this Lactobacillus Reuteri alters the level of inflammation in different compartments of the mother and the infant.

Detailed Description
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The purpose of this project is to better understand the following issues: How does bacteria transmit from the mother to the fetus and placenta during pregnancy and to the infant during the first 2-6 weeks after birth? Does colonization of the pregnant mother and fetus/Child occur? How and when? Can orally given probiotic bacteria be found in the newborn 2-6 weeks after birth, and if so where? How is bacteria transported from the mother's intestinal lumen to the Child/fetus gut? What impact has these bacteria on the level of inflammation in maternal and fetal compartments, especially that normally seen in the intestine of all newborns? What impact has these bacteria in the bowel on a normal intestinal flora establishment?

Official Title
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Lactobacillus Reuteri Feasibility Study on Probiotic Lozenges, Probiotic Chewing Gum and Probiotic Capsules and Perinatal Microbiome Seeding During Pregnancy

Conditions
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Pregnancy

Intervention / Treatment
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* Drug: Probiotic lozenges
* Drug: Placebo lozenges
* Drug: Probiotic capsules
* Drug: Placebo capsules
* Drug: Probiotic chewing gum


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Single or multiple gestation Maternal age > or = 18 y Exclusion Criteria: Known structural or chromosomal fetal malformation or abnormality Occlusive placenta previa, placenta previa in the anterior wall of the uterus, suspicion of accreta/increta/percreta infiltration Unable to understand information about the study due to language or severe mental disease Known Hepatitis B, C, HIV Known immunosuppressive illness if they are under treatment Treatment with cytokine, methotrexate or immunosuppresses cytotoxics in the last 6 months before the study. Gastro-intestinal surgery including gastric bypass or huge intestinal resection. Anaphylactic shock Uterus malformation that occludes cervical Canal or uterus segment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: probiotic lozenge<br>Two probiotic lozenges per day (morning and evening) after meals. Enrollment will be done in gestational week 28-36. The treatment will last for the rest of pregnancy and six weeks post partum. | Drug: Probiotic lozenges<br>* The women participating in the study will take two probiotic lozenges per day (morning and evening) after meals.Enrollment will be done in gestational week 28-36. The treatment will last for the rest of pregnancy and six weeks post partum.<br>* Other names: Lactobacillus reuteri lozenges;|
| Active Comparator: Probiotic capsule<br>Two probiotic capsules per day (morning and evening) after meals. Enrollment will be done in gestational week 28-36. The treatment will last for the rest of pregnancy and six weeks post partum. | Drug: Probiotic capsules<br>* The women participating in the study will take two probiotic capsules per day (morning and evening) after meals. Enrollment will be done in gestational week 28-36. The treatment will last for the rest of pregnancy and six weeks post partum.<br>* Other names: Lactobacillus reuteri capsules;|
| Active Comparator: Probiotic chewing gum<br>The probiotic chewing gum should be chewed on for about 10 minutes. Enrollment will be done in gestational week 28-36. The treatment will last for the rest of pregnancy and six weeks post partum. | Drug: Probiotic chewing gum<br>* The women participating in the study will take two probiotic chewing gums per day (morning and evening) after meals. Enrollment will be done in gestational week 28-36. The treatment will last for the rest of pregnancy and six weeks post partum.<br>* Other names: Lactobacillus reuteri chewing gum;|
| Placebo Comparator: Placebo lozenge<br>Two placebo lozenges per day (morning and evening) after meals. Enrollment will be done in gestational week 28-36. The treatment will last for the rest of pregnancy and six weeks post partum. | Drug: Placebo lozenges<br>* The women participating in the study will take two placebo lozenges per day (morning and evening) after meals. Enrollment will be done in gestational week 28-36. The treatment will last for the rest of pregnancy and six weeks post partum.<br>* Other names: non active treatment lozenges;|
| Placebo Comparator: Placebo capsule<br>Two placebo capsules per day (morning and evening) after meals. Enrollment will be done in gestational week 28-36. The treatment will last for the rest of pregnancy and six weeks post partum. | Drug: Placebo capsules<br>* The women participating in the study will take two placebo capsules per day (morning and evening) after meals. Enrollment will be done in gestational week 28-36. The treatment will last for the rest of pregnancy and six weeks post partum.<br>* Other names: non active treatment capsules;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of Lactobacillus reuteri in different compartments in the mother and the Child. | Both cultivation techniques for the specific bacteria and metagenomic techniques will be used to be able to study both cultivable and non-cultivable bacteria. | Mother: From weeks 28-36 of pregnancy until 6 weeks post partum. Child: from birth till 4 years old. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Levels of Toll-like receptor stimulated with Lactobacillus plantarum, Pseudomonas aeruginosa and LPS after probiotic treatment and after placebo in different maternal and neonatal compartments. | To evaluate whether there are differences in Toll-like receptor stimulation with Lactobacillus plantarum, Pseudomonas aeruginosa and LPS in different compartments between women treated with probiotic and the placebo group | Mother: From weeks 28-36 of pregnancy until 6 weeks post partum. Child: from birth till 4 years old. | 
| Levels of IL-6, IL-10, IL-1beta, MCP-1, IL-17, TNF-alfa after probiotic treatment and after placebo in different maternal and neonatal compartments. | To evaluate whether there are differences in the levels of cytokines and chemokines in different compartments between women treated with probiotic and the placebo group | Mother: From weeks 28-36 of pregnancy until 6 weeks post partum. Child: from birth till 4 years old. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Microbiome, probiotic