HCR.20.064 – MICROSTART: establishing a healthy gut microbiome in preterm newborns in the western world

Route: Health care research, sickness prevention and treatment

Cluster question: 086 Intestinal disorders, and specifically the relationship between gut flora and health: what can we do to benefit our gut flora?

Research question: What is the relation between the gut microbiome and early life health and disease status in preterm infants, and which factors contribute to positive health outcomes in proof of concept nutritional and microbiota-based interventions? The newborn gut microbiome plays a critical role in healthy development. The interplay between nutrition, gut microbiota, and large numbers of metabolic and immune mediators is at the basis of both normal and perturbed immune-function in the neonatal period. In particular, preterm infants have an immature gut and their standard extended exposure to antibiotics deepens intestinal dysbiosis, limiting the efficacy of nutritional interventions to prevent sepsis, necrotizing enterocolitis and intestinal failure, and to reduce risks of chronic inflammatory and auto-immune diseases, including asthma, obesity, allergy, and impaired neuromotor outcome. A major barrier to elucidating the critical nutrition-host-microbiome interactions and reducing neonatal mortality is the paucity of multi-stacked metagenomics and metabolomics insight. We propose a multidisciplinary consortium, MICROSTART, to explore the correlation between the gut microbiome, early life health and disease status in preterm infants, to determine which factors contribute to positive health outcomes and to test proof of concept interventions with targeted pre/probiotics, initially in animal models and organoids. A large-scale (> 20.000) clinical cohort of pre-term and neonatal samples (infant feces and maternal milk) will be used, combined with state-of-the-art analytical and bioinformatic tools, to determine microbial and metabolic mediators of intestinal health status in infants and neuromotor outcome in infancy. This project builds on a unique longitudinal collection of fecal material from >2000 (still recruiting) preterm and term neonates from 9 Neonatal Intensive Care Units throughout the Netherlands and on maternal milk and feces collected from 120 mother-infant dyads.
Persons involved: Prof. dr. Age Smilde FNWI-UvA Biosystems Data Analysis (data analyst), Prof. dr. Paul Lucassen FNWI-UvA Structural and Functional Plasticity of the Nervous System (neurobiologsist), Dr. Harm Krugers FNWI-UvA Structural and Functional Plasticity of the Nervous System (neurobiologsist), Dr. Aniko Korosi Nutrition and development; FNWI Structural and Functional Plasticity of the Nervous System. Structural and Functional Plasticity of the Nervous System (Human milk and infant fecal cohort), Prof. dr. Hans van Goudoever Head Emma Children’s Hospital AMC (early life nutrition therapy expert maternal milk, development and the milk microbiome), Prof. dr. Mark Benninga A UMC Department of Pediatrics. Pediatrician (Infant care), Dr. Tim de Meij A UMC Department of Pediatrics Pediatrician (Infant care preterm Cohort), Dr. Joep Derickx A UMC Department of Pediatrics (Pediatric Surgeon), prof. dr. Wouter de Jonge Tytgat Institute A UMC (AMC) (Gut micro & clinical research), Dr. Jurgen Seppen Tytgat Institute A UMC (AMC) (Gut micro / mycobiome), Dr. Bruno Sovran Tytgat Institute A UMC (AMC) (Gut micro / mycobiome), Dr. Hilde Herrema PI Microbiota Centre A UMC (AMC) – (16S rRNA core facility), Dr. Elisa Beninca RIVM Host-Microbe Interaction (modelling microbial host ecology), Dr. Ferry Hagen Westerdijk Institute for Fungal Biodiversity (Mycologist), Prof. dr. Leen Stougie CWI, Group Leader Life Science and Health (Mathematics, biological network analysis), Dr. Nanda Piersma lector Urban Analytics (HvA Machine learning, data analysis), Dr. Kenneth van Driel lector BioCenter (HAN Microbiology, diagnostics and data analysis), Artis-Micropia Prof. Remco Kort (chair at VU) and Dr. Jasper Buikx, Outreach

Keywords

cohort, microbiome, NEC, nutrition, obesity and (neurological)development, preterm babies

Other organisations

Amsterdam UMC, CWI, Emma Children's Hospital AMC, HAN, HVA, Outreach, Rijksinstituut voor Volksgezondheid en Milieu (RIVM), UvA, Vrije Universiteit Amsterdam (VU), Westerdijk Institute for Fungal Biodiversity

Submitter

Organisation University of Amsterdam
Name Prof. dr. S. (Stanley) Brul
E-mail s.brul@uva.nl
Website https://sils.uva.nl/content/research-groups/ami/ami.html