Probiotics to extremely low birth weight infants: the PROPEL trial

SNIC 2019/3-351


SNIC Medium Compute

Principal Investigator:

Thomas Abrahamsson


Linköpings universitet

Start Date:


End Date:


Primary Classification:

30109: Microbiology in the medical area



Although the care of premature infants has improved during the last decades, still about 30 percent of the extreme low birth weight (ELBW, birth weight <1000g) infants die. Severe infections and necrotizing enterocolitis (NEC) are common causes of death in this population. The gut microbiota is believed to be particularly perturbed in preterm children because of the widespread use of antibiotics and the artificial environment that intensive care unit. Antibiotics have been linked to NEC development, and studies have shown that the diversity of the gut microbiota falls the week before the onset of sepsis and NEC. The overall purpose of this project is to investigate the importance of the gut microbiota and the effect of probiotics and early nutrition on health and disease in extreme premature infants. The relationship between the composition of the gut microbiome in ELBW infants and clinical outcomes such as feeding tolerance, growth, neurological development and severe complications such as NEC, infections and bronchopulmonary disease will be analysed by analysing phylogenetic and functional bacterial genes with high-throughput next generation sequencing methods. The effect of oral supplementation with the probiotic bacteria L. reuteri on gastrointestinal function and neurological outcome will be evaluated in in a in a prospective double-blinded placebo-controlled trial (PROPEL trial). The cohort is based on a clinical trial evaluating probiotic treatment in 134 extreme premature infants. The enrolled infants are very well characterized with comprehensive clinical data including growth, feeding intolerance, use of enteral and parenteral nutrition, treatment, antibiotics and complications. Stool samples were collected at 1, 2, 3 and 4 weeks of age and at gestational week 36 and at 2 years of age. Stool samples are also collected from healthy full term infants at the same chronological ages as controls. The project needs SNIC resources in the NGS analyses of the gut microbiota. The research group has two post docs with microbiology and bioinformatics skills working full time with these analyses. Microbial phylogenetic characterization with NGS analyses is soon finalized in all 134 infants (approx. 700 samples) in our lab at Linköping University. The next step is to make functional bacterial analyses with shotgun metagenomics in collaboration with Science for Life lab. In the first round in total 48 samples from 48 infants iwere sequenced for the shotgun analyses. We have just shipped another 192 samples for sequencing for the next step i the project. T TIME TABLE: The phylogenetic analyses are running. Bioinformatic analyses of the shotgun metagenomics started in January 2019. We have a one-year support from NBIS. We are going th analyses the next step of during the next 12 months.