Probiotics and Early Microbial Contact in Preterm Neonates (ProPre)

• Gut microbiota [ Time Frame: 1 month ] [ Designated as safety issue: No ]
  Assessment of indigenous intestinal microbiota composition in premature neonates during the first month of life
• Intestinal immunity [ Time Frame: 1 month ] [ Designated as safety issue: No ]
  Investigation of neonatal intestinal immune gene expression from fecal samples during the first month of life.
• Breast milk composition [ Time Frame: 1 month ] [ Designated as safety issue: No ]
  Measurement of microbiological and immunological properties of breast milk.

Probiotics are live microbes which, when administered in sufficient amounts, confer a health benefit to the host. According to recent clinical trials, administration of probiotics to very low birth weight infants significantly reduces overall mortality and risk of necrotizing enterocolitis, a devastating inflammatory intestinal disease. The investigators have previously demonstrated that administering probiotics to the lactating mother enhances the immunoprotective properties of breast milk. Despite the promising data, the optimal probiotic intervention is yet to be established. The mechanisms by which probiotics exert their effects remain largely unknown.

This research project is based on the notion that modulation of early microbial contact by probiotics may provide a safe and effective means to improve the health of preterm infants. In particular, the investigators hypothesize that the protective potential of probiotics may be enhanced via breast milk by administering probiotics to the lactating mother. All of the potentially beneficial effects of probiotic bacteria are strain-specific and therefore preliminary laboratory and clinical research with regard to different physiological targets of probiotic intervention should be carried out to guide the design of large-scale clinical trials aiming show clinical efficacy and establish clinical practice. The purpose of this research project is to identify targets for probiotic therapy in premature neonates and to provide insight into the optimal probiotic strains and administration protocol the clinical efficacy of which will subsequently be tested in a randomized controlled trial.

The specific aims of the project are:

1. To determine the effect of maternal consumption of probiotics during lactation on immunomodulatory properties of breast milk in mothers of premature infants. Concentrations of immunomodulatory factors and microbiological properties of breast milk will be measured.
2. To investigate the impact of different probiotic administration protocols on gut microbiota composition in preterm infants. In particular, the issue whether maternal probiotic consumption instead or in addition to probiotics administered to the infant is effective will be elucidated. Different potential probiotic strains will be assessed.
3. To elucidate the impact probiotic bacteria administered to the lactating mother and/or directly to the infant on gut immunophysiology in preterm infants.

• Premature; Infant, Light-for-dates
• Breastfeeding

• Dietary Supplement: LGG
  Lactobacillus rhamnosus GG 10E9 cfu / day
• Dietary Supplement: La+Bb
  A combination of probiotic lactobacilli and bifidobacteria administered 10E9 cfu / day.
• Dietary Supplement: Placebo
  Microcrystalline cellulose is used as placebo.

• Active Comparator: LGG mother - LGG infant
  The probiotic LGG is administered both to the lactating mother and her infant.
  Intervention: Dietary Supplement: LGG
• Active Comparator: placebo mother - LGG infant
  Placebo is administered to the lactating mother whilst the infant receives the probiotic LGG.
  Intervention: Dietary Supplement: LGG
• Placebo Comparator: placebo mother - placebo infant
  Placebo is administered to both the lactating mother and her infant.
  Intervention: Dietary Supplement: Placebo
• Active Comparator: LGG mother - placebo infant
  The probiotic LGG is administered to the lactating mother whilst the infant receives placebo.
  Intervention: Dietary Supplement: LGG
• Active Comparator: LaBb mother - LaBb infant
  A combination of lactobacilli and bifidobacteria is administered both to the lactating mother and her infant.
  Intervention: Dietary Supplement: La+Bb
• Active Comparator: LaBb mother - placebo infant
  A combination of lactobacilli and bifidobacteria is administered to the lactating mother whilst the infant receives placebo.
  Intervention: Dietary Supplement: La+Bb
• Active Comparator: Pacebo mother - LaBb infant
  Placebo is administered to the lactating mother, the infant receives a combination of lactobacilli and bifidobacteria.
  Intervention: Dietary Supplement: La+Bb

Inclusion Criteria:

• premature infant born at <35 weeks gestational age

Exclusion Criteria:

• severe asphyxia
• significant anomalies

• University of Turku
• Massachusetts General Hospital