Probiotics to extremely low birth weight infants: the PROPEL trial

SNIC 2018/3-329


SNAC Medium

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 60 infants will be selected for the shotgun analyses (180 samples). The selection will be based on clinical outcomes of specific interest such as NEC, fast and slow growth and poor neurological outcome. TIME TABLE: The phylogenetic analyses are running. We planned to start the shotgun metagenomics in December 2017 when our new post doc with these particular skills should have arrived. However, it turned out that she could not come to our lab until May 2018. That is the reason we did not use the resources we ha applied for in December 2017. We have now just placed an order to the NGI portal for whole genome sequencing and will thereby need the researches we are applying for within 1-2 months, when they have made the sequencing.