Clinical trial NCT02693028: Lactobacillus Reuteri Feasibility Study on Probiotic Treatment and Perinatal Microbiome
Official title: Lactobacillus Reuteri Feasibility Study on Probiotic Lozenges, Probiotic Chewing Gum and Probiotic Capsules and Perinatal Microbiome Seeding During Pregnancy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pregnancy
Keywords: Microbiome
probiotic
Lead sponsor: Sahlgrenska University Hospital
Sponsor class: OTHER
Collaborators: name: BioGaia AB
First posted: 2016-02-26
Enrollment: 30
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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: The purpose of this project is to better understand the following issues:

1. 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?
2. Does colonization of the pregnant mother and fetus/Child occur? How and when?
3. Can orally given probiotic bacteria be found in the newborn 2-6 weeks after birth, and if so where?
4. How is bacteria transported from the mother's intestinal lumen to the Child/fetus gut?
5. 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?
6. What impact has these bacteria in the bowel on a normal intestinal flora establishment?

Eligibility criteria: 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.

Primary outcomes:
measure: Presence of Lactobacillus reuteri in different compartments in the mother and the Child.
timeFrame: Mother: From weeks 28-36 of pregnancy until 6 weeks post partum. Child: from birth till 4 years old.
Secondary outcomes:
measure: 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.
timeFrame: Mother: From weeks 28-36 of pregnancy until 6 weeks post partum. Child: from birth till 4 years old.
measure: 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.
timeFrame: Mother: From weeks 28-36 of pregnancy until 6 weeks post partum. Child: from birth till 4 years old.
Other outcomes:
Locations:
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital
Study officials:
affiliation: Göteborg University
name: Bo Jacobsson, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yeganegi M, Leung CG, Martins A, Kim SO, Reid G, Challis JR, Bocking AD. Lactobacillus rhamnosus GR-1 stimulates colony-stimulating factor 3 (granulocyte) (CSF3) output in placental trophoblast cells in a fetal sex-dependent manner. Biol Reprod. 2011 Jan;84(1):18-25. doi: 10.1095/biolreprod.110.085167. Epub 2010 Sep 1.
citation: Aagaard K, Ma J, Antony KM, Ganu R, Petrosino J, Versalovic J. The placenta harbors a unique microbiome. Sci Transl Med. 2014 May 21;6(237):237ra65. doi: 10.1126/scitranslmed.3008599.
citation: Cobo T, Kacerovsky M, Palacio M, Hornychova H, Hougaard DM, Skogstrand K, Jacobsson B. Intra-amniotic inflammatory response in subgroups of women with preterm prelabor rupture of the membranes. PLoS One. 2012;7(8):e43677. doi: 10.1371/journal.pone.0043677. Epub 2012 Aug 20.
citation: Goncalves LF, Chaiworapongsa T, Romero R. Intrauterine infection and prematurity. Ment Retard Dev Disabil Res Rev. 2002;8(1):3-13. doi: 10.1002/mrdd.10008.
citation: Jimenez E, Fernandez L, Marin ML, Martin R, Odriozola JM, Nueno-Palop C, Narbad A, Olivares M, Xaus J, Rodriguez JM. Isolation of commensal bacteria from umbilical cord blood of healthy neonates born by cesarean section. Curr Microbiol. 2005 Oct;51(4):270-4. doi: 10.1007/s00284-005-0020-3. Epub 2005 Sep 20.
citation: Jimenez E, Marin ML, Martin R, Odriozola JM, Olivares M, Xaus J, Fernandez L, Rodriguez JM. Is meconium from healthy newborns actually sterile? Res Microbiol. 2008 Apr;159(3):187-93. doi: 10.1016/j.resmic.2007.12.007. Epub 2008 Jan 11.
citation: Myhre R, Brantsaeter AL, Myking S, Gjessing HK, Sengpiel V, Meltzer HM, Haugen M, Jacobsson B. Intake of probiotic food and risk of spontaneous preterm delivery. Am J Clin Nutr. 2011 Jan;93(1):151-7. doi: 10.3945/ajcn.110.004085. Epub 2010 Oct 27.
citation: Brantsaeter AL, Myhre R, Haugen M, Myking S, Sengpiel V, Magnus P, Jacobsson B, Meltzer HM. Intake of probiotic food and risk of preeclampsia in primiparous women: the Norwegian Mother and Child Cohort Study. Am J Epidemiol. 2011 Oct 1;174(7):807-15. doi: 10.1093/aje/kwr168. Epub 2011 Aug 5.
citation: Bertelsen RJ, Brantsaeter AL, Magnus MC, Haugen M, Myhre R, Jacobsson B, Longnecker MP, Meltzer HM, London SJ. Probiotic milk consumption in pregnancy and infancy and subsequent childhood allergic diseases. J Allergy Clin Immunol. 2014 Jan;133(1):165-71.e1-8. doi: 10.1016/j.jaci.2013.07.032. Epub 2013 Sep 10.
citation: Yeganegi M, Watson CS, Martins A, Kim SO, Reid G, Challis JR, Bocking AD. Effect of Lactobacillus rhamnosus GR-1 supernatant and fetal sex on lipopolysaccharide-induced cytokine and prostaglandin-regulating enzymes in human placental trophoblast cells: implications for treatment of bacterial vaginosis and prevention of preterm labor. Am J Obstet Gynecol. 2009 May;200(5):532.e1-8. doi: 10.1016/j.ajog.2008.12.032. Epub 2009 Mar 14.